Drug-eluting stents: A study of international practice.

Austin D, Oldroyd KG, Holmes DR, Rihal CS, Galbraith PD, Ghali WA, Legrand V, Taeymans Y, McConnachie A, Pell JP, on behalf of the APPROACH Investigators, Belgian Working Group on Invasive Cardiology, Mayo Clinic PCI Registry, and Scottish Coronary Revascularisation Registry Glasgow, United Kingdom; Rochester, MN; Calgary, Canada; and Liege, and Gent, Belgium. Drug-eluting stents: A study of international practice. Am Heart J 2009;158:576-84.

Objective: We aimed to analyze trends in drug-eluting stents (DES) use in four international health care and regulatory settings.

Background: Accounts suggest a differential approach to DES internationally and recent reductions in use following reports of late stent thrombosis. Current studies of clinical practice are limited in their scope.

Methods: Data were pooled from angioplasty registries in Alberta (Canada), Belgium, Mayo Clinic (Rochester, MN), and Scotland (UK) that have routinely recorded consecutive patients treated since 2003. Trend analysis was performed to examine variations in DES use over time and by clinical subgroup.

Results: A total of 178,504 lesions treated between January 2003 and September 2007 were included. In the Mayo Clinic Registry, rapid adoption to a peak of 91% DES use for all lesions by late 2004 was observed. In contrast, Alberta and Scotland showed delayed adoption with lower peak DES use, respectively, 56% and 58% of lesions by early 2006. Adoption of DES in Belgium was more gradual and peak use of 35% lower than other registries. Reductions in DES use were seen in all data sets during 2006, although this varied in absolute and relative terms and by clinical subgroup.

Conclusion: Adoption and use of DES showed wide variation in four countries. The determinants of use are complex, and it is likely that nonclinical factors predominate. Recent reductions in use may be as a consequence of publicity and concerns regarding late stent thrombosis. The optimum application of DES in clinical practice is unclear and is reflected in the degree of international variation demonstrated. (Am Heart J 2009;158:576-84.)


Preoperative statin use and infection after cardiac surgery: a cohort study

Mohamed R, McAlister FA, Pretorius V, Kapoor AS, Majumdar SR, Ross DB, and Norris CM for the APPROACH Investigators. Preoperative statin use and infection after cardiac surgery: a cohort study. Clin Infect Dis. 2009 Apr 1;48(7):e66-72.

Background: It has been suggested that the routine use of statins preoperatively would reduce the risk of postoperative infection. We conducted this study to explore whether preoperative statin use was associated with infection after cardiac surgery (recipients of which have a higher-than-average risk of postoperative infection).

Methods: We performed secondary analysis of data collected in a prospective cohort study of adults who underwent nontransplant cardiac surgery in a university hospital during the period January 1999 through December 2005. Outcomes were ascertained in a blinded and independent fashion.

Results: Of the 7733 patients, 2657 (34%) were taking statins preoperatively; the proportion increased from 16% during 1999–2000 to 53% during 2003–2005 (P<.001, by test for trend). There was no association between preoperative statin use and postoperative infection: 214 statin users (8.1%) versus 425 statin nonusers (8.4%) developed an infection within 30 days after surgery. Factors associated with increased risk of infection after cardiac surgery included diabetes mellitus, heart failure, chronic obstructive pulmonary disease, increasing age, elevated baseline creatinine level, and longer duration of cardiopulmonary bypass but not statin use (adjusted odds ratio, 1.08; 95% confidence interval, 0.89–1.31).

Conclusions: Preoperative statin use was not associated with a reduction in the rate of postoperative infection among patients who underwent cardiac surgery. This lack of apparent benefit for high-risk patients argues against the routine use of statins as a preoperative strategy for lower-risk patients and supports calls for randomized trials to define whether preoperative statin use influences postoperative rates of infection.


Elevated Body Mass Index and Use of Coronary Revascularization after Cardiac Catheterization

King KM, Southern DA, Cornuz J, Maitland A, Knudtson, ML, Ghali WA. Elevated Body Mass Index and Use of Coronary Revascularization after Cardiac Catheterization. Am J Med 2009 Mar;122(3):273-80.

Background: Obese persons suffer discrimination in society that may extend to health care use. We investigated whether overweight and obese patients are as likely to undergo coronary reperfusion or revascularization as patients of normal body weight.

Methods: Detailed clinical data were collected for an inception cohort of patients from Alberta, Canada, who underwent cardiac catheterization between April 2001 and March 2004. The patients' likelihood of receiving any revascularization, percutaneous coronary intervention, or coronary artery bypass graft surgery in the year after cardiac catheterization was examined on the basis of body mass index (BMI) grouping. Use of revascularization was examined separately for patients with high- and low-risk coronary disease.

Results: Of 27,460 patients who had BMI data recorded, 24% were of normal weight, 42% were overweight, and 35% were obese. Although overweight and obese patients were more likely to have percutaneous coronary intervention (adjusted hazard ratio [HR] = 1.07, 95% confidence interval [CI], 1.01-1.12 and HR 1.08, 95% CI, 1.01-1.13, respectively), obese patients (BMI > 30) were less likely to receive coronary artery bypass graft surgery (adjusted HR = 0.93, 95% CI, 0.87-1.00). This was primarily because of less use of coronary artery bypass graft surgery for the most obese patients (obesity class III) with low-risk coronary anatomy (adjusted HR = 0.61, 95% CI, 0.36-1.02).

Conclusions: The pattern of use of revascularization procedures after cardiac catheterization differs somewhat across BMI subgroups. These differences might be clinically appropriate, but they warrant further exploration.


Long term outcomes of patients receiving drug eluting stents

Philpott A, Southern DA, Clement FM, Galbraith PD, Traboulsi M, Knudtson ML, Ghali WA for the APPROACH Investigators. Long term outcomes of patients receiving drug eluting stents. CMAJ 2009 Jan: 180(2);167-174.

Background: We sought to establish the long-term safety of drug-eluting stents compared with bare-metal stents in a usual care setting.

Methods: Using data from a prospective multicentre registry, we compared rates of death and of death or repeat revascularization during 3 years of follow-up of 6440 consecutive patients who underwent angioplasty with either drug-eluting or bare-metal stents between Apr. 1, 2003 and Mar. 31, 2006.

Results: Drug-eluting stents were inserted in 1120 patients and bare-metal stents in 5320. The drug-eluting stents were selected for patients who had a greater burden of comorbid illness, including diabetes mellitus (32.8% v. 20.8% in the bare-metal group, p < 0.001) and renal disease (7.4% v. 5.0%, p = 0.001). At 1-year follow-up, the drug-eluting stents were associated with a mortality of 3.0%, as compared with 3.7% with the bare-metal stents (adjusted odds ratio [OR] 0.62, 95% confidence interval [CI] 0.46–0.83). The rate of the composite outcome of death or repeat revascularization was 12.0% for the drug-eluting stents and 15.8% for the bare-metal stents (adjusted OR 0.40, 95% CI 0.33– 0.49). In the subgroup of patients who had acute coronary syndromes, the adjusted OR for this composite outcome was 0.46 (95% CI 0.35–0.61). During the 3 years of observation, the relative risks for death and repeat revascularization varied over time. In year 1, there was an initial period of lower risk in the group with drug-eluting stents than in the group with bare-metal stents; this was followed by a shift toward outcome rates favouring bare-metal stents in years 2 and 3. The adjusted relative risk of the composite outcome of death or repeat revascularization associated with drug-eluting stents relative to bare-metal stents was 0.73 early in the first year of follow-up; it then rose gradually over time, to a peak of 2.24 at 3 years.

Interpretation: Drug-eluting stents are safe and effective in the first year following insertion. Thereafter, the possibility of longer term adverse events cannot be ruled out.


Diagnostic accuracy and impact of computed tomographic coronary angiography on utilization of invasive coronary angiography

Chow BJW, Abraham A, Wells GA, Chen L, Ruddy TD, Yam Y, Govas N, Galbraith PD, Dennie C, Beanlands RS. Diagnostic accuracy and impact of computed tomographic coronary angiography on utilization of invasive coronary angiography. CIRC Cardiovasc Imaging 2009: 2;16-23.

Background: Computed tomographic coronary angiography (CTA), given its high negative predictive value, is a potential gatekeeper for invasive coronary angiography (ICA). Before CTA can be further accepted into clinical practice, its impact on healthcare resources needs to be better understood. We sought to determine the clinical impact of CTA on ICA referrals, CTA accuracy, and normalcy rate.

Methods & Results: To determine the impact of CTA, consecutive patients (n=7017) undergoing ICA before and after implementing a dedicated cardiac CT program were reviewed and compared with 3 other centers (n=11 508). To determine CTA accuracy, we evaluated consecutive CTA patients who underwent ICA. For normalcy rate, we identified patients with a low pretest probability for obstructive coronary artery disease. With the implementation of a cardiac CT program, the frequency of normal ICA decreased from 31.5% (1114 of 3538 patients) to 26.8% (932 of 3479 patients) (p<0.001). These findings were significantly different (p=0.003) from the 3 centers, in which normal ICAs were unchanged (30.0% [1870 of 6224 patients] to 31.0% [1642 of 5284 patients]). CTA had excellent per-patient sensitivity (99% [CI, 95% to 100%]), positive predictive value (92% [CI, 86% to 96%]) and negative predictive value (95% [CI, 72% to 100%]). Because of referral bias, specificity (64% [CI, 44% to 81%]) was low; however, the normalcy rate of CTA was 94% (CI, 90% to 97%). After adjusting for referral bias, the adjusted sensitivity was 90% (CI, 89% to 91%), and the adjusted specificity was 95% (CI, 94% to 96%), with positive and negative predictive values of 92% (CI, 91% to 93%) and 93% (CI, 92% to 94%), respectively.

Conclusion: The clinical implementation of CTA appears to positively impact ICA by reducing the frequency of normal ICA. The operating characteristics of CTA support its potential role as a tool useful in ruling out obstructive coronary artery disease.


Schmaltz HN, Southern DA, Maxwell CJ, Knudtson ML, Ghali WA; for the APPROACH Investigators. Patient Sex Does Not Modify Ejection Fraction as a Predictor of Death in Heart Failure: Insights from the APPROACH Cohort. J Gen Intern Med. 2008 Dec; 23(12):1940-6

Background: Normal and low ejection fraction (EF) heart failure patients appear to have similar outcomes.

Objective: The object of this study was to determine whether sex modifies the effects of left ventricular EF on prevalent heart failure mortality.

Design: Prospective cohort study.

Patients: Patients (n = 6, 095) with a diagnosis of heart failure and a measure of EF undergoing cardiac catheterization in Alberta, Canada between April 1999 and December 2004; follow-up continued through October 2005.

Measurements: All-cause mortality was assessed in analyses stratified by patient sex and EF (</=50% vs. >50%).

Main Results: Overall, female heart failure patients were older, had more hypertension, valvular disease, less systolic impairment and coronary artery disease. Baseline medication use was similar in the four sex-EF groups. Low EF heart failure mortality over 6.5 years was slightly higher but was not significantly modified by patient sex. This relationship remained unchanged after adjustment for differences in baseline characteristics and process of care (women normal EF, reference group; men normal EF adjusted HR 1.1, 95% CI 0.9-1.3; women low EF adjusted HR 1.5, 95% CI 1.1-2.0; men low EF adjusted HR 1.6, 95% CI 1.2-2.1).

Conclusions:Patient sex did not appear to modify the negative effects of low EF on long-term survival in this prospective study of prevalent heart failure. The small absolute difference in survival between low and normal EF heart failure highlights the need for further research into optimal therapy for the latter, a less well-understood condition.


Ko DT, Donovan LR, Huynh T, Rinfret S, So DY, Love MP, Galbraith D, Tu JV; Canadian Cardiovascular Outcomes Research Team (CCORT). A survey of primary percutaneous coronary intervention for patients with ST segment elevation myocardial infarction in Canadian hospitals. Can J Cardiol. 2008 Nov;24(11):839-43.

Background: Historically, access to primary percutaneous coronary intervention (PCI) for the treatment of patients with ST segment elevation myocardial infarction (STEMI) has been limited in Canada. Recent studies have identified innovative strategies to improve timely access and reduce reperfusion time. Accordingly, the contemporary use of primary PCI treatment in Canada was ascertained.

Methods: A cross-sectional survey of all 38 Canadian hospitals that were capable of performing PCI procedures was conducted from June 2007 to November 2007. The survey focused on the practice of primary PCI for patients with STEMI and whether the hospitals had implemented internal strategies to reduce 'door-to-balloon' times. Analyses were performed at the level of geographical regions.

Results: Overall, 71% of PCI hospitals (27 of 38) provided around-the-clock primary PCI for patients with STEMI, but the proportion of PCI hospitals offering this service varied widely, from 33% to 100% across regions. All Canadian PCI hospitals provided around-the-clock rescue PCI treatment to STEMI patients who had failed fibrinolytic therapy. In terms of strategies that are associated with reduced reperfusion time, it was observed that only 42% of PCI hospitals (16 of 38) provided feedback on door-to-balloon time to the emergency department and to the cardiac catheterization laboratories within one week of the primary PCI procedure. Overall, 24% of the hospitals had not adopted any of the four identified strategies to improve door-to-balloon time.

Conclusion: Although the majority of Canadian hospitals with PCI capability provide around-the-clock primary PCI for patients with STEMI, significant variations in this practice exist across the country. Canadian PCI hospitals have not consistently adopted strategies that are associated with improved door-to-balloon time.


Oreopoulos A, Padwal R, Kalantar-Zadeh K, Fonarow GS, Norris CM, McAlister FA. Body mass index and mortality in heart failure: a meta-analysis. Am Heart J 2008;156(1):13-22.

Background: In patients with chronic heart failure (CHF), previous studies have reported reduced mortality rates in patients with increased body mass index (BMI). The potentially protective effect of increased BMI in CHF has been termed the obesity paradox or reverse epidemiology. This meta-analysis was conducted to examine the relationship between increased BMI and mortality in patients with CHF.

Methods: We searched the Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, Scopus, and Web of Science to identify studies with contemporaneous control groups (cohort, case-control, or randomized controlled trials) that examined the effect of obesity on all-cause and cardiovascular mortality. Two reviewers independently assessed studies for inclusion and performed data extraction.

Results: Nine observational studies met final inclusion criteria (total n = 28,209). Mean length of follow-up was 2.7 years. Compared to individuals without elevated BMI levels, both overweight (BMI approximately 25.0-29.9 kg/m(2), RR 0.84, 95% CI 0.79-0.90) and obesity (BMI approximately > or =30 kg/m(2), RR 0.67, 95% CI 0.62-0.73) were associated with lower all-cause mortality. Overweight (RR 0.81, 95% CI 0.72-0.92) and obesity (RR 0.60, 95% CI 0.53-0.69) were also associated with lower cardiovascular mortality. In a risk-adjusted sensitivity analysis, both obesity (adjusted HR 0.88, 95% CI 0.83-0.93) and overweight (adjusted HR 0.93, 95% CI 0.89-0.97) remained protective against mortality.

Conclusions: Overweight and obesity were associated with lower all-cause and cardiovascular mortality rates in patients with CHF and were not associated with increased mortality in any study. There is a need for prospective studies to elucidate mechanisms for this relationship.


Norris CM, Hegadoren K, Patterson L, Pilote L. Sex differences in prodromal symptoms of patients with acute coronary syndrome: a pilot study. Prog Cardiovasc Nurs 2008;28(1):27-31.

Increasing evidence suggests that there are sex/gender differences in the presentation and prodromal symptoms of acute coronary syndrome (ACS). The purpose of this pilot study was to identify sex differences in the prodromal symptoms of ACS using the McSweeney Acute and Prodromal Myocardial Infarction Symptom Survey (MAPMISS). Telephone surveys using the MAPMISS were conducted between 4 and 6 months after the ACS event. Seventy-six patients (24 women) participated in the study. The women generally reported higher prodromal scores. Moreover, scores demonstrated differences in prodromal symptoms based on menopausal status. The premenopausal and perimenopausal women reported a greater number and higher frequency of symptoms compared with the men and menopausal women. The results of this study suggest that both men and women report nontraditional prodromal symptoms of ACS. In addition, there appears to be a difference in the frequency and number of symptoms reported based on menopausal status.


Oreopoulos A, Padwal R, Norris CM, Mullen JC, Pretorius V, Kalantar-Zadeh K. Effect of obesity on short- and long-term mortality post-coronary revascularization: a meta-analysis. Obesity 2008;16(2);442-450.

Objective: Overweight and obesity are often assumed to be risk factors for postprocedural mortality in patients with coronary artery disease (CAD). However, recent studies have described an "obesity paradox" -- a neutral or beneficial association between obesity and mortality postcoronary revascularization. We reviewed the effect of overweight and obesity systematically on short- and long-term all-cause mortality post-coronary artery bypass grafting (CABG) and post-percutaneous coronary intervention (PCI).

Methods: We searched the Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, Scopus, and Web of Science to identify cohort, case control, and randomized controlled studies evaluating the effect of obesity on in-hospital/short-term (within 30 days) and long-term (up to 5 years) mortality. Full-text, published articles reporting all-cause mortality between individuals with and without elevated BMI were included. Two reviewers independently assessed studies for inclusion and performed data extraction.

Results: Twenty-two cohort publications were identified, reporting results in ten post-PCI and twelve post-CABG populations. Compared to individuals with non-elevated BMI levels, obese patients undergoing PCI had lower short- (odds ratio (OR) 0.63; 95% confidence interval (CI) 0.54-0.73) and long-term mortality (OR 0.65; 95% CI 0.51-0.83). Post-CABG, obese patients had lower short-term (OR 0.63; 95% CI 0.56-0.71) and similar long-term (OR 0.88; 95% CI 0.60-1.29) mortality risk compared to normal weight individuals. Results were similar in overweight patients for both procedures.

Conclusions: Compared to non-obese individuals, overweight and obese patients have similar or lower short- and long-term mortality rates postcoronary revascularization. Further research is needed to confirm the validity of these findings and delineate potential underlying mechanisms.


Hubacek J, Kalla S, Galbraith PD, Graham MM, Knudtson ML, Ghali WA, for the APPROACH Investigators. Outcomes of revascularization strategies for two vessel coronary artery disease involving the proximal left anterior descending artery in an era of improved pharmacotherapy and stenting. Can J Cardiol 2008: 24(2);121-126.

Background: The best therapeutic strategy for patients with double-vessel coronary artery disease and proximal left anterior descending artery involvement (2VD + pLAD) is not clear.

Objectives: To compare the survival experience of a cohort of cardiac catheterization patients with 2VD + pLAD based on chosen therapeutic strategy (medical management versus percutaneous coronary intervention [PCI] versus coronary artery bypass graft surgery [CABG]).

Methods: The authors identified and studied a total of 603 patients with 2VD + pLAD from all patients who underwent diagnostic coronary angiography in Alberta between January 1997 and May 1999. The primary end point was five-year survival from index catheterization for each of the treatment groups and from time of revascularization when the two revascularization strategies were compared.

Results: Risk-adjusted hazard ratios (HR) comparing cumulative five-year survival rates of patients treated medically, or with PCI or CABG indicated a survival benefit for patients treated with CABG (HR 0.24, 95% CI 0.11 to 0.54; P<0.001) and PCI (HR 0.43, 95% CI 0.24 to 0.77; P=0.003) compared with medical management. Meanwhile, a risk-adjusted comparison of revascularization strategies suggested a possible trend toward higher mortality for PCI-treated patients versus CABG-treated patients (HR 1.56, 95% CI 0.65 to 3.72; P=0.125).

Conclusions: The results of this registry-based observational study suggest a survival benefit from revascularization compared with medical management in patients with 2VD + pLAD. Furthermore, the authors found a trend toward better survival in CABG-treated patients compared with PCI-treated patients.


Southern DA, Norris CM, Quan H, Shrive FM, Galbraith PD, Humphries K, Gao M, Knudtson ML, Ghali WA. An administrative data merging solution for dealing with missing data in a clinical registry: adaptation from ICD-9 to ICD-10. BMC Med Res Methodol. 2008 Jan 23; 8( 1): 1 [Epub ahead of print]

Background: We have previously described a method for dealing with missing data in a prospective cardiac registry initiative. The method involves merging registry data to corresponding ICD-9-CM administrative data to fill in missing data 'holes'. Here, we describe the process of translating our data merging solution to ICD-10, and then validating its performance.

Methods: A multi-step translation process was undertaken to produce an ICD-10 algorithm, and merging was then implemented to produce complete datasets for 1995-2001 based on the ICD-9-CM coding algorithm, and for 2002-2005 based on the ICD-10 algorithm. We used cardiac registry data for patients undergoing cardiac catheterization in fiscal years 1995-2005. The corresponding administrative data records were coded in ICD-9-CM for 1995-2001 and in ICD-10 for 2002-2005. The resulting datasets were then evaluated for their ability to predict death at one year.

Results: The prevalence of the individual clinical risk factors increased gradually across years. There was, however, no evidence of either an abrupt drop or rise in prevalence of any of the risk factors. The performance of the new data merging model was comparable to that of our previously reported methodology: c-statistic=0.788 (95 percent CI 0.775, 0.802) for the ICD-10 model versus c-statistic=0.784 (95 percent CI 0.780, 0.790) for the ICD-9-CM model. The two models also exhibited similar goodness-of-fit.

Conclusions: The ICD-10 implementation of our data merging method performs as well as the previously-validated ICD-9-CM method. Such methodological research is an essential prerequisite for research with administrative data now that most health systems are transitioning to ICD-10.


Makowsky MJ, McAlister FA, Galbraith PD, Southern DA, Ghali WA, Knudtson ML, Tsuyuki, RT for the Alberta Provincial Program for Outcome Assessment in Coronary Heart Disease (APPROACH) Investigators. Lower extremity peripheral arterial disease in individuals with coronary artery disease: Prognostic importance, care gaps, and impact of therapy. Am Heart J 2008;155:348-55.

Background: Our objective was to examine the effect of concomitant lower extremity peripheral arterial disease (PAD) on long-term prognosis and pharmacotherapy in patients with coronary artery disease (CAD).

Methods: Prospective cohort study enrolling all patients with angiographically proven CAD between April 1, 2000, and December 31, 2004, in Alberta, Canada.

Results: Of 28,649 patients (mean age 64 years) with CAD, 2509 (9%) had a physician-assigned diagnosis of lower extremity PAD. Mortality was higher in the patients with CAD and PAD over a mean follow-up of 3.1 years, even after adjusting for the fact that patients with PAD had more severe CAD and more comorbidities (adjusted hazard ratio [HR] 1.41, 95% CI 1.28-1.55). Fewer patients with CAD and PAD received antiplatelet agents (83% vs 86%, odds ratio 0.86, 95% CI 0.77-0.97) or β-blockers (63% vs 67%, odds ratio 0.89, 95% CI 0.82-0.98), but users of these agents exhibited lower mortality (adjusted HR 0.68, 95% CI 0.60-0.77, for antiplatelet agents and adjusted HR 0.72, 95% CI 0.64-0.80, for β- blockers). Approximately half of these patients were prescribed statins or angiotensin-converting enzyme inhibitors, and 27% were using all 3 evidence-based anti-atherosclerotic therapies (antiplatelets, statin, and angiotensin-converting enzyme inhibitor).

Conclusions: In patients with CAD, lower extremity PAD is independently associated with poorer outcomes. Although all evidence-based therapies are underused in patients with CAD, patients with concomitant PAD are less likely to be prescribed antiplatelet agents or β-blockers—both agents are associated with improved survival in patients with CAD and PAD.


Goldberg A, Southern DA, Galbraith PD, Traboulsi M, Knudtson ML, Ghali WA for the APPROACH Investigators. Coronary dominance and prognosis of patients with acute coronary syndrome. Am Heart J 2007 Dec;154:1116-22.

Background: A number of studies have identified the number of diseased vessels to be an important determinant of survival in patients with acute coronary syndrome (ACS). It is unknown if coronary dominance has an impact on prognosis of these patients. We hypothesized that the prognosis of patients with ACS with left dominance (LD) would be worse than that of patients with right or mixed dominance.

Methods: The study population consisted of 27,289 patients whose primary indication for cardiac catheterization was ACS. The patients were divided into 3 groups according to coronary dominance. The mean duration of follow-up was 3.5 years (range 1-6.5 years). A Cox proportional hazards analysis was used to compare survival by dominance, adjusting for age, sex, diagnosis, comorbidities, severity of coronary disease, and ejection fraction.

Results: The rates and patterns of revascularization among patients with significant coronary disease were similar between the groups. At the end of follow-up, patients with LD had a significantly higher mortality (hazard ratio 1.18, 95% CI 1.05-1.34; adjusted hazard ratio 1.13, CI 1.00-1.28). The mortality of patients with mixed and right dominance was similar.

Conclusion: In patients with ACS, LD is a significant and independent predictor of increased long-term mortality. Further research is needed to determine mechanisms of increased mortality in patients with LD and measures that can be taken to improve the outcome of patients with left-dominant circulation.


Patel AB, Waters NM, Ghali WA. Determining geographic areas and populations with timely access to cardiac catheterization facilities for acute myocardial infarction care in Alberta, Canada. Intl J Health Geog 2007 Oct 16, 6:47 (in production).

Background: This study uses geographic information systems (GIS) as a tool to evaluate and visualize the general accessibility of areas within the province of Alberta (Canada) to cardiac catheterization facilities. Current American and European guidelines suggest performing catheterization within 90 minutes of the first medical contact. For this reason, this study evaluates the populated places that are within a 90 minute transfer time to a city with a catheterization facility. The three modes of transport considered in this study are ground ambulance, rotary wing air ambulance and fixed wing air ambulance.

Methods: Reference data from the Alberta Chart of Call were interpolated into continuous travel time surfaces. These continuous surfaces allowed for the delineation of isochrones: lines that connect areas of equal time. Using Dissemination Area (DA) centroids to represent the adult population, the population numbers were extracted from the isochrones using Statistics Canada census data.

Results: By extracting the adult population from within isochrones for each emergency transport mode analyzed, it was found that roughly 70% of the adult population of Alberta had access within 90 minutes to catheterization facilities by ground, roughly 66% of the adult population had access by rotary wing air ambulance and that no population had access within 90 minutes using the fixed wing air ambulance. An overall understanding of the nature of air vs. ground emergency travel was also uncovered; zones were revealed where the use of one mode would be faster than the others for reaching a facility.

Conclusions: Catheter intervention for acute myocardial infarction is a time sensitive procedure. This study revealed that although a relatively small area of the province had access within the 90 minute time constraint, this area represented a large proportion of the population. Within Alberta, fixed wing air ambulance is not an effective means of transporting patients to a catheterization facility within the 90 minute time frame, though it becomes advantageous as a means of transportation for larger distances when there is less urgency.


Bainey KR, Norris CM, Graham MM, Ghali WA, Knudtson ML, Welsh RC for the APPROACH Investigators. Clinical in-stent restenosis with bare metal stents: Is it truly a benign phenomenon? Intl Journal of Cardiology, online publication August 2007.

Objective: In-stent restenosis (ISR) remains an important problem following percutaneous coronary intervention (PCI). Although it is generally believed that patients with ISR present with stable angina, this has not been well characterized. The aim of this study was to define the incidence, predictors, timing and clinical presentation of patients with ISR requiring repeat catheterization.

Design: Using a multiregion prospective database which captures all patients undergoing cardiac catheterization and revascularization in the Province of Alberta, Canada, consecutive bare metal stent (BMS) implantations from January 1, 1998 to December 31, 2002 were analyzed. All patients with a repeat angiogram within one year of the index PCI were reviewed for evidence of clinical-ISR (CISR), defined as ISR as the cause for clinical presentation at angiography.

Results: Of the 12,492 consecutive PCI patients reviewed, 2521 had repeat angiography and 744 patients (6.0%) had CISR by study definition. The mean time to repeat angiography in CISR patients was 5.4±2.7 months and multivariate analysis identified female gender, diabetes mellitus, and prior PCI as predictors. The majority of patients presented with an acute coronary syndrome: 52.2% unstable angina/non-ST elevation myocardial infarction and 18.5% ST elevation myocardial infarction. Only 25.3% presented with stable exertional angina.

Conclusion: Although the incidence of CISR within one year after BMS was relatively low, the recurrent clinical event in the majority of cases was a high-risk coronary syndrome. Thus, careful consideration of the risks of ISR to a specific patient against the cost implications of novel and expensive means to decrease its occurrence is required.


Worthley MI, Shrive FM, Anderson TJ, Traboulsi M. Prognostic Implication of Hyperglycemia in Myocardial Infarction and Primary Angioplasty. Am J Med, 2007 Jul, Vol 120, Issue 7: 643.e1-643.e7.

Purpose: The study assessed the relationship of admission blood glucose level to in-hospital mortality in patients presenting with an ST-segment elevation myocardial infarction and treated with primary angioplasty.

Methods: A total of 980 patients presenting with an ST-segment elevation myocardial infarction and treated exclusively with primary angioplasty were evaluated. Patients were divided into quartiles based on their admission blood glucose level: group 1 ( <=6.6 mmol/L [<=119 mg/dL]), group 2 (6.7-7.8 mmol/L [120-140 mg/dL]), group 3 (7.9-10.0 mmol/L [141-180 mg/dL], and group 4 (>=10.1 mmol/L [ >=181 mg/dL]. The primary end point was in-hospital mortality.

Results: The mean age of the patient cohort was 62 years, 260 (27%) of whom were female. The mean admission blood glucose level was 9.1±4.4 mmol/L (164±79 mg/dL). At admission, 16% of this group were known to have diabetes. The in-hospital mortality rate was 3.8% (n =37), 5.2% in the diabetic group (n =8) and 3.5% (n=29) in the nondiabetic group. In-hospital mortality rates were significantly increased in patients with an elevated admission blood glucose level ( P<.001). The in-hospital deaths in each admission blood glucose level quartile were 0.4% (n=1) in group 1, 2% (n=6) in group 2, 2% (n =6) in group 3, and 10% (n =24) in group 4.

Conclusions: In this cohort of patients who were admitted with an ST-segment elevation myocardial infarction and treated exclusively with primary angioplasty, elevated admission blood glucose level is significantly associated with an increase in in-hospital mortality.


Quan H, Galbraith PD, Norris CM, Southern DA, King K, Verhoef MJ, Knudtson ML, Ghali WA. Opinions on chelation therapy in patients undergoing coronary angiography: cross-sectional survey. Can J Cardiol. 2007 Jun;23(8):635-40.

Background: Chelation therapy is frequently used by patients for the treatment of coronary artery disease. However, relatively little is known about patient attitudes and beliefs that underlie the use of this treatment. The aim of the present study was to document patients' opinions and beliefs about health care decision making, physician and patient communication and relationships, and reasons for using or not using chelation therapy as treatment for coronary artery disease.

Methods: A mail survey was sent to patients who underwent coronary angiography between 1998 and 2000 in Alberta. Information was collected on self-reported reasons for chelation therapy use, sociodemographic characteristics, communication and relationships between patients and physicians, as well as beliefs regarding surgery, medications and chelation therapy.

Results: Of the 780 patients who received surveys, 96 users and 264 nonusers of chelation therapy completed questionnaires. Among the users, 20.8% believed that chelation therapy could cure heart disease, 44.2% believed that it could relieve symptoms, 16.7% believed that it could have side effects and 58.4% believed that it could increase quality of life. Users and nonusers were similar in their beliefs about safety and benefits of heart surgery, but users of chelation therapy were less likely than nonusers to believe that using conventional medications could prevent worsening of heart disease (53.1% versus 67.4%), increase quality of life (74.0% versus 85.2%) and give a feeling of control over heart disease (61.5% versus 77.7%).

Conclusions: Many chelation therapy users appeared to have negative views toward the benefits of conventional medications and positive views toward the safety of chelation therapy. Users and nonusers of chelation therapy had the same views toward the benefits and safety of heart surgery.


McAlister FA, Oreopoulos A, Norris CM, Graham MM, Tsuyuki RT, Knudtson M, Ghali WA. Exploring the Treatment-Risk Paradox in Coronary Disease. Arch Intern Med. 2007 May 28;167(10):1019-1025.

Background: The cause of the “treatment-risk paradox” reported for patients with coronary disease is unknown; however, determining the factors that contribute to this paradox is essential to properly design quality improvement interventions.

Methods: Prospective cohort study enrolling consecutive patients with angiographically proved coronary disease between February 1, 2004, and November 30, 2005, in Alberta.

Results: One month after an angiogram, statins were being taken by 2436 (62.9%) of 3871 patients (mean age, 64 years). High-risk patients were less likely to be taking statins than lower-risk patients (55.8% vs 63.5%; crude odds ratio [OR], 0.72 [95% confidence interval {CI}, 0.57- 0.92]; risk ratio [RR], 0.88 [95% CI, 0.79-0.97]), but this treatment-risk paradox was completely attenuated by adjusting for exertional capacity and depressive symptoms (OR, 0.98 [95% CI, 0.75-1.28]; RR, 0.99 [95% CI, 0.89-1.09]). These results were robust across drug classes: while high-risk patients were less likely to be taking angiotensin- converting enzyme inhibitors, aspirin, and statins (25.8% vs 32.3%; crude OR, 0.73 [95% CI, 0.56- 0.95]; RR, 0.80 [95% CI, 0.65-0.97]), this association did not persist in the adjusted model (OR, 0.98 [95% CI, 0.72- 1.33] [P=.87]; RR, 0.99 [95% CI, 0.79-1.20]).

Conclusions: The treatment-risk paradox reported in administrative database analyses is attributable to clinical factors not typically captured in these databases (such as functional capacity and depressive symptoms). Interventions to address the treatment-risk paradox should recognize that patients with reduced functional capacity, depression, or both are at higher risk for underuse of these beneficial therapies and should target physicians and patients.


Schmaltz HN, Southern D, Ghali WA, Jelinski SE, Parsons GA, King KM, Maxwell CJ. Living alone, patient sex and mortality after acute myocardial infarction. J Gen Intern Med. 2007 May;22(5):572-8.

Background: Psychosocial factors, including social support, affect outcomes of cardiovascular disease, but can be difficult to measure. Whether these factors have different effects on mortality post-acute myocardial infarction (AMI) in men and women is not clear.

Objective: To examine the association between living alone, a proxy for social support, and mortality postdischarge AMI and to explore whether this association is modified by patient sex.

Design: Historical cohort study.

Participants/Setting: All patients discharged with a primary diagnosis of AMI in a major urban center during the 1998–1999 fiscal year.

Measurements: Patients’ sociodemographic and clinical characteristics were obtained by standardized chart review and linked to vital statistics data through December 2001.

Results: Of 880 patients, 164 (18.6%) were living alone at admission and they were significantly more likely to be older and female than those living with others. Living alone was independently associated with mortality [adjusted hazard ratio (HR) 1.6, 95% confidence interval (CI) 1.0–2.5], but interacted with patient sex. Men living alone had the highest mortality risk (adjusted HR 2.0, 95% CI 1.1–3.7), followed by women living alone (adjusted HR 1.2, 95% CI 0.7–2.2), men living with others (reference, HR 1.0), and women living with others (adjusted HR 0.9, 95% CI 0.5–1.5).

Conclusions: Living alone, an easily measured psychosocial factor, is associated with significantly increased longer-term mortality for men following AMI. Further prospective studies are needed to confirm the usefulness of living alone as a rognostic factor and to identify the potentially modifiable mechanisms underlying this increased risk.


Ray JG, Norris CM, Udell JA, Tsuyuki RT, McAlister FA, Knudtson ML, Ghali WA. Lipid-lowering therapy and outcomes in heart failure. J Cardiovasc Pharmacol Ther. 2007 Mar;12(1):27-35.

Lipid-lowering therapy, particularly with statins, reduces the risk of cardiovascular mortality; however, there is uncertainty about their efficacy in patients with heart failure, including those without coronary artery stenosis. A clinical database was studied to determine whether lipid-lowering therapy is associated with improved survival in persons with heart failure—with or without concomitant coronary artery stenosis. During an 8-year period, 6060 people with a history of heart failure underwent coronary angiography. At the time of angiography, 1216 received a lipid-lowering agent. During a median follow-up of 4.7 years, 7.1 deaths per 100 person-years occurred among users of lipid-lowering therapy, compared with 7.8 per 100 person-years among nonusers (adjusted hazard ratio 0.87, 95% confidence interval 0.77-0.97). Use of lipid-lowering therapy was associated with a reduced risk of death in patients with heart failure. Current evidence supports statin use in individuals with recognized heart failure and concomitant coronary heart disease, dyslipidemia, or diabetes mellitus. More data are needed before statins can be recommended in those with isolated heart failure.


Shrive FM, Ghali WA, Johnson JA, Donaldson C, Manns BJ. Use of the U.S. and U.K. scoring algorithm for the EuroQol-5D in an economic evaluation of cardiac care. Med Care. 2007 Mar;45(3):269-73.

Background: Most studies that have used the EuroQol-5D instrument (EQ-5D) have used a scoring algorithm based on preferences solicited from the U.K. population. An algorithm recently was developed for the U.S. population, with studies showing meaningful differences in the results obtained using the 2 algorithms. We recently published an economic evaluation assessing the use of drug-eluting stents in patients undergoing percutaneous coronary intervention (PCI).

Objectives: Using the aforementioned economic evaluation, we describe the EQ-5D utility scores resulting from use of U.S. and U.K. algorithms and explore the differences in the incremental cost-utility ratio (ICER) resulting from use of the different EQ-5D estimates.

Methods: EQ-5D data were obtained from the Alberta Provincial Project for Outcomes Assessment in Coronary Heart (APPROACH) disease registry. Individual responses were scored once with each algorithm. The within-individual difference was calculated ( U.S. score - U.K. score). The mean, SD, and range were compared using paired t tests. The resulting ICERs were compared using probabilistic sensitivity analysis.

Results: The U.K. mean was statistically different from the U.S. mean (0.83, SD 0.20 vs. 0.87, SD 0.15, P < 0.001). The mean within individual difference was 0.04 with a wide range (-0.02 to +0.41). The resulting ICER are CAN $58,635 (95% confidence interval $198,248–$34,406) per quality-adjusted life year and CAN $58,229 (95% confidence interval $116,818–$38,779) per quality-adjusted life year for the U.K. and U.S. algorithms, respectively (P value: 0.07).

Conclusions: The algorithms produce quite notable differences within individuals. The effect on the mean score is less pronounced. In the context of our economic evaluation, however, the impact of using the U.S. algorithm on the ICER is negligible.


Shrive FM, Stuart H, Quan H, Ghali WA. Dealing with missing data in a multi-question depression scale: a comparison of imputation methods. BMC Med Res Methodol. 2006 Dec 13;6:57.

Background: Missing data present a challenge to many research projects. The problem is often pronounced in studies utilizing self-report scales, and literature addressing different strategies for dealing with missing data in such circumstances is scarce. The objective of this study was to compare six different imputation techniques for dealing with missing data in the Zung Self-reported Depression scale (SDS).

Methods: 1580 participants from a surgical outcomes study completed the SDS. The SDS is a 20 question scale that respondents complete by circling a value of 1 to 4 for each question. The sum of the responses is calculated and respondents are classified as exhibiting depressive symptoms when their total score is over 40. Missing values were simulated by randomly selecting questions whose values were then deleted (a missing completely at random simulation). Additionally, a missing at random and missing not at random simulation were completed. Six imputation methods were then considered; 1) multiple imputation, 2) single regression, 3) individual mean, 4) overall mean, 5) participant's preceding response, and 6) random selection of a value from 1 to 4. For each method, the imputed mean SDS score and standard deviation were compared to the population statistics. The Spearman correlation coefficient, percent misclassified and the Kappa statistic were also calculated.

Results: When 10% of values are missing, all the imputation methods except random selection produce Kappa statistics greater than 0.80 indicating 'near perfect' agreement. MI produces the most valid imputed values with a high Kappa statistic (0.89), although both single regression and individual mean imputation also produced favorable results. As the percent of missing information increased to 30%, or when unbalanced missing data were introduced, MI maintained a high Kappa statistic. The individual mean and single regression method produced Kappas in the 'substantial agreement' range (0.76 and 0.74 respectively).

Conclusion: Multiple imputation is the most accurate method for dealing with missing data in most of the missing data scenarios we assessed for the SDS. Imputing the individual's mean is also an appropriate and simple method for dealing with missing data that may be more interpretable to the majority of medical readers. Researchers should consider conducting methodological assessments such as this one when confronted with missing data. The optimal method should balance validity, ease of interpretability for readers, and analysis expertise of the research team.


Bagshaw SM, Galbraith PD, Mitchell LB, Sauve R, Exner DV, Ghali WA. Prophylactic amiodarone for prevention of atrial fibrillation after cardiac surgery: a meta-analysis. Ann Thorac Surg. 2006 Nov;82(5):1927-37.

Amiodarone has been proposed to decrease atrial fibrillation after cardiac surgery. The literature was systematically reviewed for randomized trials comparing amiodarone with control for prevention of atrial fibrillation. Data were extracted on study characteristics, quality, and incidence of atrial fibrillation, cardiovascular outcomes, and length of hospitalization. Nineteen trials were included. Amiodarone reduced the odds ratio of atrial fibrillation (0.50; 95% confidence interval [CI]: 0.43 to 0.59, p < 0.0001), ventricular tachyarrhythmias (0.39; 95% CI: 0.26 to 0.58, p < 0.0001), and strokes (0.53; 95% CI: 0.30 to 0.92, p = 0.02). Amiodarone reduced hospital stay (0.6 days; 95% CI: 0.4 to 0.8, p < 0.0001). Amiodarone decreased atrial fibrillation, reduced perioperative ventricular tachyarrhythmias and strokes, and reduced duration of hospitalization. The current evidence supports recommending the routine use of perioperative amiodarone for cardiac surgery.


Southern DA, Faris PD, Brant R, Galbraith PD, Norris CM, Knudtson ML, Ghali WA, for the APPROACH Investigators. Southern DA, Faris PD, Brant R, Galbraith PD, Norris CM, Knudtson ML, Ghali WA, for the APPROACH Investigators. Kaplan - Meier methods yielded misleading results in competing risk scenarios. J Clin Epidemiol 2006 Oct; 59(10):1110-4.

Background & Objective: Time-to-event curves are routinely presented in the medical literature. The most widely used method is the KaplaneMeier (K-M) method, but this analysis approach may not be appropriate when an analysis focuses on time-to-first event in scenarios where there are competing events. We compared K-M methods applying various censoring approaches with the lesser-known ‘‘cumulative incidence competing risks’’ (CICR) method in an analysis of competing events.

Methods: A registry containing data on 21,624 patients undergoing cardiac catheterization was analyzed. Time to coronary artery bypass grafting (CABG) was assessed in an analysis for which percutaneous coronary intervention and death were competing events. Time-to-CABG curves were calculated using the ‘‘K-M censor all method,’’ ‘‘K-M censor death only method,’’ ‘‘K-M ignore all method,’’ and the CICR method.

Results: One-year CABG rates calculated for the K-M ‘‘censor all,’’ ‘‘censor death only,’’ and ‘‘ignore all’’ methods were 28.8%, 22.8%, and 22.4%, respectively compared to the ‘‘actual’’ rate of 20.8%. For the CICR method, the corresponding 1-year rate was identical to the ‘‘actual’’ rate.

Conclusion: In situations with competing risks, and where an analysis focuses on first events, the CICR method is most appropriate, as K-M methods will tend to overestimate event rates.


Tsuyuki RT, Shrive FM, Galbraith PD, Knudtson ML, Graham MM, for the APPROACH Investigators. Revascularization in Patients with Heart Failure. CMAJ 2006 Aug. 15; 175(4):361-5.

Background: Although practice guidelines recommend coronary revascularization for patients with heart failure, the evidence to support this recommendation is weak. The objective of our study was to determine the association of coronary revascularization with survival in patients who have had heart failure.

Methods: Data were obtained from the Alberta Provincial Project for Outcomes Assessment in Coronary Heart Disease (APPROACH), a clinical outcome–monitoring initiative that has captured data on all patients undergoing cardiac catheterization in the province of Alberta since 1995. Our study included data from patients with a history of heart failure and with documented coronary artery disease; patients with normal coronary arteries or prior coronary artery bypass grafting (CABG) were excluded. We constructed survival curves and adjusted them by the corrected group prognosis method (incorporating all clinical variables in APPROACH). Propensity scores were used to account for clinical characteristics that could influence the decision to revascularize.

Results: A total of 2538 patients (mean age 68 yr, standard deviation [SD] 11 yr, 31% female) underwent revascularization; 1690 patients (mean age 69 [SD 11] yr, 34% female) did not. Crude 1-year mortality was 11.8% among patients who underwent revascularization, compared with 21.6% among those who did not. Adjusted survival curves diverged early and continued up to 7 years of follow-up (hazard ratio 0.50, 95% confidence interval 0.44–0.57). Propensity scores showed improved survival with revascularization across all quintiles of likelihood of revascularization.

Interpretation: This new evidence lends support to practice guidelines, which recommend revascularization in patients with heart failure and coronary disease.


Knudtson, ML, Beanlands R, Brophy JM, Higginson L, Munt B, Rottger J on behalf of the Candian Cardiovascular Society Access to Care Working Group. Treating the right patient at the right time: Access to specialist consultation and noninvasive testing. Can J Cardiol 2006 Aug;22(10):819-824.

The Council of the Canadian Cardiovascular Society commissioned working groups to examine issues of access to, and wait times for, various aspects of cardiovascular care. The present article summarizes the deliberations on targets for medically acceptable wait times for access to cardiovascular specialist evaluation and on the performance of noninvasive testing needed to complete this evaluation. Three categories of referral indications were identified: those requiring hospitalization due to substantial ongoing risk of mortality and morbidity; those requiring an expedited early review in an ambulatory setting; and, finally, a larger category in which delays of two to six weeks can be justified. The proposed wait time targets will provide guidance on the timeliness of care to busy clinicians charged with the care of patients with cardiovascular disease, help policy makers appreciate the clinical challenges in providing access to high quality care, and highlight the critical need for a thoughtful review of cardiology human resource requirements. Wait time implementation suggestions are also included, such as the innovative use of disease management and special need clinics. The times proposed assume that available clinical practice guidelines are followed for clinical coronary syndrome management and for treatment of associated conditions such as hypertension, diabetes, renal disease, smoking cessation and lipid disorders. Although media attention tends to focus on wait times for higher profile surgical procedures and high technology imaging, it is likely that patients face the greatest wait-related risk at the earlier phases of care, before the disease has been adequately characterized.


Ross H, Howlett J, Arnold JM, Liu P, O'Neill BJ, Brophy JM, Simpson CS, Sholdice MM, Knudtson M, Ross DB, Rottger J, Glasgow K; Canadian Cardiovascular Society Access to Care Working Group. Treating the right patient at the right time: access to heart failure care. Can J Cardiol. 2006 Jul;22(9):749-54.

Heart failure affects over 500,000 Canadians, and 50,000 new patients are diagnosed each year. The mortality remains staggering, with a five-year age-adjusted rate of 45%. Disease management programs for heart failure patients have been associated with improved outcomes, the use of evidence-based therapies, improved quality of care, and reduced costs, mortality and hospitalizations. Currently, national benchmarks and targets for access to care for cardiovascular procedures or office consultations do not exist. The present paper summarizes the currently available data, particularly focusing on the risk of adverse events as a function of waiting time, as well as on the identification of gaps in existing data on heart failure. Using best evidence and expert consensus, the present article also focuses on timely access to care for acute and chronic heart failure, including timely access to heart failure disease management programs and physician care (heart failure specialists, cardiologists, internists and general practitioners).


Graham MM, Knudtson ML, O'Neill BJ, Ross DB for the Canadian Cardiovascular Society Access to Care Working Group. Treating the right patient at the right time: Access to cardiac catheterization, percutaneous coronary intervention and cardiac surgery. Can J Cardiol 2006 July; 22(8): 679-683.

The Canadian Cardiovascular Society Access to Care Working Group was formed with a mandate to use the best science and information available to establish reasonable triage categories and safe wait times for common cardiovascular services and procedures through a series of commentaries. The present commentary discusses the rationale for access benchmarks for cardiac catheterization and revascularization procedures for patients with stable angina, and access benchmarks for cardiac catheterization and surgery for patients with valvular heart disease. Literature on standards of care, wait times and wait list management was reviewed. A survey of cardiac centres in Canada was performed to develop an inventory of current practices in identifying and triaging patients. The Working Group recommends the following medically acceptable wait times for access to cardiac catheterization: 14 days for symptomatic aortic stenosis and six weeks for patients with stable angina and other valvular disease. For percutaneous coronary intervention in stable patients with high-risk anatomy, immediate revascularization or a wait time of 14 days is recommended; six weeks is recommended for all other patients. The target for bypass surgery in those with high-risk anatomy or valve surgery in patients with symptomatic aortic stenosis is 14 days; for all others, the target is six weeks. All stakeholders must affirm the appropriateness of these standards and work continuously to achieve them. There is an ongoing need to continually reassess current risk stratification methods to limit adverse events in patients on waiting lists and assist clinicians in triaging patients for invasive therapies.


Graham MM, Norris CM, Galbraith PD, Knudtson ML, Ghali WA. Quality of life after coronary revascularization in the elderly. Eur Heart J 2006 July; 27(14):1690-8.

Aims: To describe health status outcomes at 4 years for a cohort of elderly patients with cardiac disease.

Methods & Results: Using the Alberta Provincial Project for Outcomes Assessment in Coronary Heart Disease, an outcomes initiative capturing all patients undergoing cardiac catheterization in Alberta, Canada, health status was measured using the Seattle Angina Questionnaire (SAQ) and crude and risk-adjusted outcomes were determined and compared for patients treated with percutaneous coronary intervention or coronary artery bypass surgery (CABG) vs. medical therapy. Response rates among surviving, consenting patients were 64.8% for patients<70 years (n=7883), 77.3% for patients aged 70–79 years (n=2940), and 77.7% for patients >=80 years of age (n=439). For patients aged <70 years, and those aged 70–79 years, for all dimensions of the SAQ, scores were significantly better for patients treated with revascularization procedures than with medical therapy. For patients over the age of 80 years, scores for patients treated with CABG in particular were significantly better, with the exception of exertional capacity. At 3 years, all scores remained stable or improved, and continued to favour revascularization.

Conclusion: Elderly patients undergoing revascularization have better health status at 4 years than do those in the same age group who do not undergo revascularization. These findings suggest that age should not deter against revascularization given the combined survival and quality-of-life benefits.


Gyenes G, Shrive FM, Graham MM, Ghali WA, Knudtson ML for the APPROACH Investigators. The Prognostic Importance of Nonsignificant Left Main Coronary Artery Disease in Patients Undergoing Percutaneous Coronary Intervention. J Am Coll Cardiol. 2006 Jul 18;48(2):276-80.

Objectives: The purpose of this research was to study the association between nonsignificant (<50%) left main coronary artery disease (LMCAD) and short- and long-term survival in patients undergoing percutaneous coronary intervention (PCI).

Background: The prognostic importance of nonsignificant LMCAD is unknown; however, the coexistence of nonsignificant LMCAD may influence revascularization decisions.

Methods: We analyzed mortality and repeat catheterization rates of 11,855 patients in a prospective cardiac registry database who underwent single-vessel or multivessel PCI from January 1996 through December 2001. Of this cohort, 11.7% (n = 1,385) had nonsignificant (<50%) LMCAD. Outcomes were compared with those without LMCAD. A secondary analysis was performed on a larger cohort of 34,586 patients undergoing cardiac catheterization, irrespective of mode of revascularization therapy.

Results: Patients with nonsignificant LMCAD had more co-morbidities, and a significantly higher crude mortality rate at 1 year compared with those without LMCAD (4.4% vs. 3.4%; p = 0.05). The 7-year crude mortality hazard ratio (HR) of PCI patients with <50% LMCAD versus those with no LMCAD was 1.18 (95% confidence interval [CI] 0.94 to 1.46). After risk adjustment for differences in baseline clinical profile, however, the HR decreased to 0.98 (95% CI 0.79 to 1.23). Repeat catheterization rates at 1 year did not differ between groups. The secondary analysis in all patients with nonsignificant LMCAD showed an adjusted HR of 1.03 (95% CI 0.94 to 1.14).

Conclusions: Patients undergoing single-vessel or multivessel PCI who have <50% LMCAD have a nonsignificantly increased 18% relative risk for mortality compared with those without detectable LMCAD that appears to be related to these patients’ higher incidence of co-morbidities rather than the left main stenosis itself.


McAlister FA, Ghali WA, Gong Y, Fang J, Armstrong PW, Tu JV. Aspirin use and outcomes in a community-based cohort of 7352 patients discharged after first hospitalization for heart failure. Circulation. 2006 Jun 6;113(22):2572-8.

Background: The safety of aspirin in heart failure (HF) has been called into question, particularly in those patients (1) without coronary disease, (2) with renal dysfunction, or (3) treated with low-dose angiotensin-converting enzyme (ACE) inhibitors and high-dose aspirin.

Methods & Results: We examined prescription patterns and outcomes (all-cause mortality and/or HF readmission) in patients discharged from 103 Canadian hospitals between April 1999 and March 2001 after a first hospitalization for HF. Of 7352 patients with HF (mean age, 75 years; 44% without coronary disease and 29% with renal dysfunction), 2785 (38%) died or required HF readmission within the first year. Compared with nonusers, aspirin users were no more likely to die or require HF readmission (hazard ratio [HR], 1.02 [0.91 to 1.16]), even in patients without coronary disease (HR, 0.98 [0.78 to 1.22]) or patients with renal dysfunction (HR, 1.13 [0.94 to 1.36]). On the other hand, users of ACE inhibitors were less likely to die or require HF readmission (HR, 0.87 [0.79 to 0.96]), even if they were using aspirin (HR, 0.86 [0.77 to 0.95]). There were no dose-dependent interactions between aspirin and ACE inhibitors.

Conclusions: In this observational study, aspirin use was not associated with an increase in mortality rates or HF readmission rates, and aspirin did not attenuate the benefits of ACE inhibitors, even in patients without coronary disease, patients with renal dysfunction, or patients treated with high-dose aspirin and low-dose ACE inhibitors.


Hemmelgarn BR, Southern DA, Humphries KH, Culleton BF, Knudtson ML, Ghali WA for the APPROACH Investigators. Refined characterization of the association between kidney function and mortality in patients undergoing cardiac catheterization. Eur Heart J 2006 May;27(10):1191-7.

Aims: Chronic kidney disease is associated with an increased risk of cardiovascular morbidity and mortality. The level of kidney function at which this risk increases remains to be determined. We sought to characterize the relationship between kidney function and survival among patients with cardiovascular disease (CVD) undergoing cardiac catheterization using estimated glomerular filtration rate (eGFR) and graded refinements in the classification of kidney function.

Methods & Results: We included 8,521 of 11,778 (72.3%) consecutive patients undergoing cardiac catheterization between 1 January 1999 and 31 December 2001 from the Alberta Provincial Project for Outcome Assessment in Coronary Heart Disease database. eGFR as a categorical and continuous variable was used to define kidney function. The outcome was all-cause mortality. During a median (interquartile range) follow-up of 2.2 (1.5–3.1) years, and after adjustment for clinical risk factors and severity of coronary disease, there was a steady incremental decrease in survival post-catheterization corresponding to a decline in eGFR categories of 10 mL/min/1.73 m 2. When eGFR was modelled as a continuous variable, there was an increased risk of death noted at an eGFR below 79 mL/min/1.73 m 2. Below an eGFR of 70 mL/min/1.73 m 2, there was an approximate 17.2% relative increase in risk for every 10 unit decrease in eGFR (95% CI 8.4–26.6%).

Conclusion: The risk of death post-cardiac catheterization is elevated when eGFR is <=79 mL/min/ 1.73 m 2. These findings provide considerable refinement in our understanding of eGFR as a powerful prognostic marker in patients with CVD undergoing cardiac catheterization.


Norris CM, Ghali WA, Saunders LD, Brant R, Galbraith D, Faris P, Knudtson ML, for the APPROACH Investigators. Ordinal regression model and the linear regression model were superior to the logistic regression models. J Clin Epidemiol 2006 May; 59(5):448-56.

Objective: Ordinal scales often generate scores with skewed data distributions. The optimal method of analyzing such data is not entirely clear. The objective was to compare four statistical multivariable strategies for analyzing skewed health-related quality of life (HRQOL) outcome data. HRQOL data were collected at 1 year following catheterization using the Seattle Angina Questionnaire (SAQ), a disease-specific quality of life and symptom rating scale.

Study Design & Setting:In this methodological study, four regression models were constructed. The first model used linear regression. The second and third models used logistic regression with two different cutpoints and the fourth model used ordinal regression. To compare the results of these four models, odds ratios, 95% confidence intervals, and 95% confidence interval widths (i.e., ratios of upper to lower confidence interval endpoints) were assessed.

Results: Relative to the two logistic regression analysis, the linear regression model and the ordinal regression model produced more stable parameter estimates with smaller confidence interval widths.

Conclusion: A combination of analysis results from both of these models (adjusted SAQ scores and odds ratios) provides the most comprehensive interpretation of the data.


Quan H, Wang F, Schopflocher D, Norris C, Galbraith PD, Faris P, Graham MM, Knudtson ML, and Ghali WA. Development and Validation of a Surname List to Define Chinese Ethnicity. Medical Care. 2006 Apr;44(4):328-33.

Objective: Surnames have the potential to accurately identify ancestral origins as they are passed on from generation to generation. In this study, we developed and validated a Chinese surname list to define Chinese ethnicity.

Methods: We conducted a literature review, a panel review, and a telephone survey in a randomly selected sample from a Canadian city in 2003 to develop a Chinese surname list. The list was then validated to data from the Canadian Community Health Survey. Both surveys collected information on self-reported ethnicity and surname.

Results: Of the 112,452 people analyzed in the Canadian Community Health Survey, 1.6% were self-reported as Chinese. This was similar to the 1.5% identified by the surname list. Compared with self-reported Chinese ethnicity (reference standard), the surname list had 77.7% sensitivity, 80.5% positive predictive value, 99.7% specificity, and 99.6% negative predictive value. When stratifying by sex and marital status, the positive predictive value was 78.9% for married women and 83.6% for never married women.

Conclusions: The Chinese surname list appears to be valid in identifying Chinese ethnicity. The validity may depend on the geographic origins and Chinese dialects in given populations.


Southern DA, Faris PD, Knudtson ML, Ghali, WA, for the APPROACH Investigators. Prognostic relevance of census-derived individual respondent incomes versus household incomes. Can J Public Health 2006 Mar-Apr; 97(2):114-7.

Background: Census-based measures of income derived from median income of a geographic area are often used in health research. Many national census surveys gather information on both the respondent's individual income and the income for the entire household, giving researchers a choice of census income measures. We compared the extent to which individual respondent income and household income (both obtained from census data) are associated with outcomes in a cohort of patients with cardiac disease.

Methods: Methods: We used data from the Alberta Provincial Project for Outcome Assessment in Coronary Heart Disease (APPROACH), where postal codes were linked to the Postal Code Conversion File (PCCF) to determine each patient's census Dissemination Areas (DA). DA-derived median household income and median individual income were obtained from the 2001 Canadian Census and survival outcomes were then directly determined for income groupings defined by quintile. Two-year survival adjusted for age and sex was described with a proportional hazards analysis.

Results: There were 9,397 patients undergoing cardiac catheterization between January 1, 2001 and March 31, 2002, with complete DA-level median income measures. Household income quintiles yielded a wider spread of survival across quintiles (range of 2-year estimated survival, 91.8% to 95.9% for household income versus 92.8% to 95.6% for respondent income), as well as a more progressive decline in survival as income decreased. This progressive decline was not seen for the respondent income measure.

Conclusions: The greater spread and progressive decline of survival for household income relative to respondent income leads us to conclude that household income is the better socio-economic determinant of health in our data and for the outcome measure we studied.


Hubacek J, Galbraith PD, Gao M, Humphries K, Graham MM, Knudtson ML, Ghali WA for the APPROACH Investigators. External validation of a percutaneous coronary intervention mortality prediction model in patients with acute coronary syndromes. Am Heart J 2006 Feb;151:308-15.

Background: The recently published Michigan outcome prediction model (MM) for inhospital mortality was developed and validated on a series of consecutive patients undergoing percutaneous coronary intervention (PCI). Our purpose was to externally validate the performance of the MM in 2 separate cohorts of patients with acute coronary syndrome (ACS) undergoing PCI in Canada.

Methods: A validation of the MM and development of an extended MM were performed on data describing 10,050 patients from the APPROACH prospective cohort study between January 1995 and December 2000. Performance of both models was assessed on an external data set of 3259 PCI cases from the British Columbia Cardiac Registries. Only patients with a diagnosis of ACS were included in the study.

Results: The original MM predicted death rates ranging from 0.1% to 60.6%, but lacked accuracy to predict inhospital mortality as severity increased. The extended MM predicted death rates more widely from 0.0% to a high of 91.0% with better accuracy to predict inhospital death in patients with ACS undergoing PCI. The areas under the receiver operating characteristic curve for the MM and the extended MM on the external validation data set were 0.93 and 0.95, respectively.

Conclusions: The MM predicts death after PCI in patients with ACS and identifies a clear gradient of risk. However, the enhanced MM developed specifically for the subset of patients with ACS demonstrated better prediction and cross-validated performance. These prediction rules can be useful for risk-adjustment analyses and for prognostication for individual patients.


Southern DA, Knudtson ML, Ghali, WA, for the APPROACH Investigators. Myocardial Infarction on Snow Days: Incidence, Procedure Use and Outcomes. Can J Cardiol 2006 Jan; 22(1):59-61.

Background: Snowfall can cause chaos in urban centres and put considerable stress on health care systems. Given that myocardial infarction (MI) is a condition that may be triggered or aggravated by stress, and that health system stress could influence the typical care provided to patients with MI, a study was conducted comparing 'snow days' with 'nonsnow days', specifically assessing the incidence of MI, the use of acute procedures and in-hospital mortality.

Methods: Hospital discharge data were used on all patients discharged after MI. These data were merged with data from Environment Canada to determine the amount of snowfall that occurred on any given day. The use of acute procedures was determined by linking to data from the Alberta Provincial Project for Outcomes Assessment in Coronary Heart disease (APPROACH). Snow days were defined as days when at least 5 cm of snow fell, and the two subsequent days were included because of the lingering effect of 'urban chaos' that can ensue after significant snowfall. The average incidence of MIs on snow days versus nonsnow days was then determined. Risk-adjusted odds ratios for the use of direct percutaneous coronary intervention and in-hospital mortality were also determined.

Results: There were 61 snow days and 575 nonsnow days. The incidence of MI (incidence density ratio of 1.08, 95% CI 0.82 to 3.10) and the use of direct percutaneous coronary intervention (adjusted OR=1.07, 95% CI 0.74 to 1.54) were slightly higher on snow days. In-hospital mortality trended toward being lower (adjusted OR=0.54, 95% CI 0.28 to 1.04) for patients admitted on snow days, although none of these differences were statistically significant.

Conclusions: Despite the potential for the significant adverse effects of snow days on the incidence of MI, the use of acute precedures and outcomes, these findings suggest only minor effects, if any.


Southern DA, McLaren L, Hawe P, Knudtson ML, Ghali, WA, for the APPROACH Investigators. Individual-Level and Neighborhood-Level Income Measures: Agreement and Association With Outcomes in a Cardiac Disease Cohort. Med Care 2005 Nov; 43:1116–1122.

Background: Census-based measures of income often are used as proxies for individual-level income. Yet, the validity of such area-based measures relative to ‘true’ individual-level income has not been fully characterized. Objectives: The objectives of this study were (1) to determine whether area-based measures of household income area suitable proxy for self-reported household income and (2) to assess whether these measures are associated with outcomes in a cardiac disease cohort.

Research Design: We used a prospective cohort from the Alberta Provincial Project for Outcome Assessment in Coronary Heart Disease (APPROACH©) cardiac catheterization registry.

Subjects: A total of 4,372 patients having undergone cardiac catheterization and who also completed a 1-year follow-up questionnaire on self-reported income level were studied.

Measures: Our measurements were survival to 2.5 years after catheterization and health-related quality of life (EuroQoL).

Results: Agreement between the 2 income measures generally was poor (unweighted Kappa =0.07), particularly for the low-income patients. Despite this poor agreement, both income measures were positively associated with survival and EuroQoL scores. An outcome analysis that simultaneously considered individual-level income and area-based income revealed that low-income individuals have poorer survival and lower quality of life scores if they live in low income neighborhoods, but not if they live in high income neighborhoods.

Conclusions: The area-based estimates of household income in these data demonstrate poor agreement with self-reported household income at the level of individual patients, particularly for low-income patients. Despite this, both income measures appear to be prognostically relevant, perhaps because individual and neighborhood income measure different constructs.


McLellan CS, Ghali WA, Labinaz M, Davis R, Galbraith D, Southern D, Shrive F, Knudtson ML, for the APPROACH Investigators. Association between completeness of percutaneous coronary revascularization and post-procedure outcomes. Am Heart J 2005 Oct; 150(4):800-806.

Background: Multivessel coronary artery revascularization may be accomplished by percutaneous coronary intervention (PCI) or coronary artery bypass graft surgery (CABG). The importance of complete revascularization is emphasized in the surgical literature, but little is known about its impact on PCI outcomes. This study evaluated multivessel PCI patients to determine the predictors of complete revascularization and the association of complete revascularization with survival, subsequent CABG, and repeat PCI.

Methods: The Alberta Provincial Project for Outcomes Assessment in Coronary Heart Disease (APPROACH) is a clinical data collection and outcome-monitoring initiative capturing all patients undergoing cardiac catheterization and revascularization in the province of Alberta, Canada. Characteristics and long-term outcomes of 1308 patients undergoing multivessel PCI with complete revascularization were compared with those of 648 patients with incomplete revascularization.

Results: The significant independent predictors of complete revascularization were pre-PCI Duke jeopardy score, the presence of a total occlusion, year of PCI, age N 65 years, renal failure, and left ventricular function. With a median follow-up time of 3.0 F 1.8 years, the adjusted hazard ratio (HR) (95% CI) for the association between complete revascularization and outcome was 0.75 (0.54-1.04) for death, 0.55 (0.37-0.84) for subsequent CABG, and 0.93 (0.65-1.34) for repeat PCI.

Conclusions: Baseline angiographic characteristics and other clinical factors can predict complete revascularization in patients undergoing multivessel PCI. Complete multivessel PCI is associated with reduced need for future CABG, a trend toward better survival, and no difference in repeat PCI.


Alagiakrishnan K, Beitel JD, Graham MM, Southern DA, Knudtson ML, Ghali WA, Tsuyuki RT for the APPROACH Investigators. Relation of T-Axis Abnormalities to Coronary Artery Disease and Survival after Cardiac Catheterization. Am J Cardiol 2005 Sep 1; 96:639-642.

We investigated the association of an abnormal T axis with angiographic indicators of coronary artery disease and mortality. In univariate analysis, no significant association was observed between an abnormal T axis and extent of coronary artery disease (p=0.928). An abnormal T axis was a significant predictor of overall mortality (p=0.035) for death at any time in our unadjusted survival analysis, and a trend toward poorer survival persisted after adjustment for clinical covariates.


Shrive FM, Ghali WA, Lewis S, Donaldson C, Knudtson ML, Manns BJ. Moving beyond the cost per quality-adjusted life year: Modelling the budgetary impact and clinical outcomes associated with the use of sirolimus-eluting stents. Can J Cardiol 2005;21(9): 783-787.

Restenosis is a major limitation to the long-term success of percutaneous coronary intervention. Drug-eluting stents are the most recent technological advance in restenosis prevention. While they are effective, their use is associated with a significant incremental cost, and a recent economic evaluation performed by the authors suggested that their use is associated with a cost per quality-adjusted life year of $58,721. How should decision-makers react to this value, particularly given that the use of sirolimus-eluting stents appears more attractive in certain patient subgroups, such as those with complex coronary lesions? In the present paper, the authors explore an alternative method of presenting the results of the economic evaluation, rather than the usual cost per quality-adjusted life year rubric, in an attempt to assist decision-makers in deciding whether, and for whom, to fund sirolimus-eluting stents. Several issues that decision-makers and providers may wish to consider when making such funding decisions are discussed.


Graham MM, Ghali WA, Faris PD, Galbraith PD, Tu JV, Norris CM, Zentner A, Knudtson ML. Population rates of cardiac catheterization and yield of high-risk coronary artery disease. CMAJ 2005 Jul 5; 173 (1):35-39.

Background: The optimal population rate of cardiac catheterization is unknown. One potential way to determine it would be to examine whether there is a population rate beyond which the yield of high-risk coronary artery disease (CAD) does not rise.

Methods: Using a detailed clinical registry that captures all patients undergoing cardiac catheterization in Alberta, we determined annual population rates of cardiac catheterization and the corresponding yield of cases of high-risk CAD in each of Alberta’s 17 health regions from 1995 to 2002. Least squares linear regression analysis and hierarchical modelling methods were then used to assess the linear relation between catheterization rates and rates of high-risk CAD.

Results: The age-adjusted average rate of cardiac catheterization among men ranged from 404.9 to 638.1 per 100 000 population aged over 20 years. Among women, the average rate ranged from 171.8 to 314.0 per 100 000. For both sexes, increased regional rates of catheterization were associated with a linearly increasing yield of high-risk CAD, with no evidence of a plateau in yield when more procedures were performed. One additional case of high-risk CAD was identified for every 2.5 additional cardiac catheterization procedures performed among men, and for every 3.7 additional procedures performed among women.

Interpretation: The increasing yield of patients with high-risk CAD associated with increased regional population rates of cardiac catheterization, together with the absence of a plateau in yield, suggests that Alberta’s population rates of cardiac catheterization are suboptimal to detect people with high-risk CAD.


Humphries KH, Carere RG, Izadnegahdar M, Galbraith PD, Knudtson ML, Ghali WA. Cross-provincial use of cardiac services: The importance of data-sharing for clinical registries and outcomes research. Can J Cardiol 2005 Mar 1;21(3):267-272.

Background: The structure of the Canadian health care system lends itself to health services and health outcomes research. It is possible to track hospital admissions and discharges, physician billings and prescriptions using administrative databases. In addition, several provinces have developed registries that provide detailed clinical and procedural information. Using the unique personal health numbers assigned to all Canadian residents, linkage between administrative databases and population-based clinical registries provides important information regarding the use of health services and health outcomes.

Objective: To determine the extent of cross-border (British Columbia-Alberta border) use of cardiac services by British Columbia residents.

Methods: Population rates of cardiac procedures were calculated using two prospective clinical registries (British Columbia Cardiac Registries and Alberta Provincial Project for Outcome Assessment in Coronary Heart Disease [APPROACH]), as well as administrative databases (the British Columbia Ministry of Health’s hospitalization and Medical Services Plan databases).

Results: Analyses using only British Columbia data suggest low cardiac procedure rates for patients living in eastern British Columbia. By accessing APPROACH data, it was determined that more than 80% of British Columbia cardiac patients living along the British Columbia-Alberta border access procedural services in Alberta.

Conclusions: While residents of eastern British Columbia appear to have reduced access to cardiac services when data from British Columbia are analyzed in isolation, they are actually accessing care in Alberta. Analyses based solely on single province data sources will underestimate cardiac procedures rates.


Shrive, FM, Manns BJ, Galbraith PD, Knudtson ML, Ghali WA; Economic evaluation of sirolimus-eluting stents. CMAJ 2005 Feb 1; 172 (3): 345-351.

Background: Sirolimus-eluting stents have recently been shown to reduce the risk of restenosis among patients who undergo percutaneous coronary intervention (PCI). Given that sirolimus-eluting stents cost about 4 times as much as conventional stents, and considering the volume of PCI procedures, the decision to use sirolimus-eluting stents has large economic implications.

Methods: We performed an economic evaluation comparing treatment with sirolimus-eluting and conventional stents in patients undergoing PCI and in subgroups based on age and diabetes mellitus status. The probabilities of transition between clinical states and estimates of resource use and health-related quality of life were derived from the Alberta Provincial Project for Outcome Assessment in Coronary Heart Disease (APPROACH) database. Information on effectiveness was based on a meta-analysis of randomized controlled clinical trials (RCTs) comparing sirolimus-eluting and conventional stents.

Results: Cost per quality-adjusted life year (QALY) gained in the baseline analysis was Can$58 721. Sirolimus-eluting stents were more cost-effective in patients with diabetes and in those over 75 years of age, the costs per QALY gained being $44 135 and $40 129, respectively. The results were sensitive to plausible variations in the cost of stents, the estimate of the effectiveness of sirolimus-eluting stents and the assumption that sirolimus-eluting stents would prevent the need for cardiac catheterizations in the subsequent year when no revascularization procedure was performed to treat restenosis.

Interpretation: The use of sirolimus-eluting stents is associated with a cost per QALY that is similar to or higher than that of other accepted medical forms of therapy and is associated with a significant incremental cost. Sirolimus-eluting stents are more economically attractive for patients who are at higher risk of restenosis or at a high risk of death if a second revascularization procedure were to be required.


Cornuz, J, Faris P, Galbraith PD; Knudtson ML, Ghali WA; Absence of bias against smokers in access to coronary revascularization after cardiac catheterization. Int J Qual Health Care 2005 Feb;17(1)37-42.

Objective: Many consider smoking to be a personal choice for which individuals should be held accountable. We assessed whether there is any evidence of bias against smokers in cardiac care decision-making by determining whether smokers were as likely as non-smokers to undergo revascularization procedures after cardiac catheterization.

Design: Prospective cohort study.

Subjects & Setting:All patients undergoing cardiac catheterization in Alberta, Canada.

Main Measures: Patients were categorized as current smokers, former smokers, or never smokers, and then compared for their risk-adjusted likelihood of undergoing revascularization procedures (percutaneous coronary intervention or coronary artery bypass grafting) after cardiac catheterization.

Results: Among 20,406 patients undergoing catheterization, 25.4% were current smokers at the time of catheterization, 36.6% were former smokers, and 38.0% had never smoked. When compared with never smokers (reference group), the hazard ratio for undergoing any revascularization procedure after catheterization was 0.98 (95% CI 0.93–1.03) for current smokers and 0.98 (0.94–1.03) for former smokers. The hazard ratio for undergoing coronary artery bypass grafting was 1.09 (1.00–1.19) for current smokers and 1.00 (0.93–1.08) for former smokers. For percutaneous coronary intervention, the hazard ratios were 0.93 (0.87–0.99) for current smokers and 1.00 (0.94–1.06) for former smokers.

Conclusion: Despite potential for discrimination on the basis of smoking status, current and former smokers undergoing cardiac catheterization in Alberta, Canada were as likely to undergo revascularization procedures as catheterization patients who had never smoked.


Larsen AI, Galbraith PD, Ghali WA, Norris CM, Graham MM, Knudtson ML. Characteristics and outcomes of patients with acute myocardial infarction and angiographically normal coronary arteries. Am J Cardiol 2005 Jan15; 95:261-263.

This study on patients undergoing coronary angiography for acute myocardial infarction demonstrated that 2.8% of patients had angiographically normal coronary arteries and that these patients have a better prognosis than patients with angiographically verified coronary artery disease. The trend toward a higher prevalence of malignancy in this unique patient group raises the possibility of malignancy-induced hypercoagulability or inflammation as an underlying etiologic factor.


Thompson CR, Humphries KH, Gao M, Galbraith PD, Norris C, Carere RG, Knudtson ML, Ghali WA (Canadian Cardiovascular Outcomes Research Team); Revascularization use and survival outcomes after cardiac catheterization in British Columbia and Alberta. Can J Cardiol. 2004 Dec14;20(14):1417-23.

Background: Alberta and British Columbia have comprehensive cardiac databases that provide detailed demographic, clinical and procedural data, including coronary anatomy, on all patients undergoing cardiac catheterization.

Objectives: To examine the baseline clinical characteristics of patients undergoing cardiac catheterization, describe the use of revascularization treatments (percutaneous coronary intervention [PCI] and coronary artery bypass grafting [CABG]) following catheterization, and describe survival after cardiac catheterization, stratified by treatment strategy received and proposed, using cardiac databases from Alberta and British Columbia.

Patients & Methods: All patients between 20 and 105 years of age, admitted to hospital for their first coronary angiography between April 1, 1995, and March 31, 2001, with angiographic evidence of coronary disease were included in the study. Procedure volumes, baseline characteristics and therapy received within one year of cardiac catheterization are described by province. Stepwise, multivariate logistic regression analysis was used to model determinants of the revascularization modality. Kaplan-Meier curves of one-year survival after index cardiac catheterization were estimated for the therapy received ( Alberta and British Columbia) and the therapy proposed ( British Columbia only).

Results: Patients were predominantly men (70%), commonly presented with two- or three-vessel disease, and frequently had hypertension, a history of myocardial infarction and dyslipidemia. Within one year of catheterization, 21% to 26% underwent CABG and 32% to 42% underwent PCI. Emergency or urgent status at the time of catheterization was associated with receiving PCI, while three-vessel and left main disease were associated with receiving CABG. Patients who did not undergo revascularization within one year (presumed medical therapy) had the lowest one-year survival rate (93.4%; 95% CI 92.1% to 94.7%); this group comprised patients receiving medical therapy as proposed (one-year survival rate of 95.7%, 95% CI 94.6% to 96.8%), as well as patients receiving medical therapy at variance with the proposal for revascularization (84.6%; 95% CI 80.5% to 88.9%).

Conclusions: Between 53.1% and 67.5% of patients presenting for cardiac catheterization undergo revascularization within one year. Urgent status increased the probability of PCI, and anatomy (ie, three-vessel and left main) increased the probability of CABG. Patients not undergoing proposed revascularization by one year had poorer outcomes, in contrast with those proposed for medical therapy, who had excellent outcomes.


Norris CM, Jensen LA, Galbraith PD, Graham MM, Daub WD, Knudtson ML, Ghali WA. Referral Rate and Outcomes of Cardiac Rehabilitation After Cardiac Catheterization in a Large Canadian City. Journal of Cardiopulmonary Rehabilitation 2004 Nov/Dec;24:392-400.

Purpose: The benefits of cardiac rehabilitation (CR) for patients with coronary artery disease are extensive and compelling, demonstrating reductions in mortality. However, some reports suggest that only 10% to 20% of eligible patients currently participate in formal CR programs. The purpose of this study was to identify the proportion of patients referred to CR in a large Canadian city, and to determine their statistically adjusted survival rates relative to patients not referred to CR.

Methods: Subjects eligible for this study included all adult residents with coronary artery disease from 1995 to 1999 in the Alberta Provincial Project for Outcome Assessment in Coronary Heart Disease registry. All 5,081 patients who survived 6 months or more after catheterization were included in the analysis. Survival data were adjusted using a Cox proportional hazards model.

Results: Referral to a CR program (28.9% of patients) was significantly more likely for young male patients who had undergone a prior revascularization procedure, presented with an ejection fraction exceeding 50%, and did not report cerebrovascular, peripheral vascular, or renal disease. Crude hazard ratios indicated that referral to a CR program remained significantly associated with lower mortality after control was used for clinical, anatomic, treatment and comorbid conditions recorded at catheterization (hazard ratio, 0.68; 95% confidence interval, 0.51-0.90; P = .005).

Conclusions: Despite the proven efficacy of CR in clinical trials, fewer than one third of the patients undergoing cardiac catheterization are referred to a CR program. The better survival outcomes noted for patients referred to CR suggests that there is an opportunity to improve care and outcomes through increased referral of patients to such programs.


Ezekowitz J, McAlister FA, Humphries KH, Norris CM, Tonelli M, Ghali WA, Knudtson ML, for the APPROACH Investigators. The association between renal insufficiency, pharmacotherapy, and outcomes in 6,437 patients with heart failure and coronary artery disease. Journal of the American College of Cardiology. 2004 Oct19;44:1587-92.

Objectives: This study was designed to examine the use of cardiovascular medications and outcomes in patients with heart failure (HF) and renal dysfunction.

Background: Renal insufficiency is associated with poorer outcomes in patients with HF, but the mechanisms are uncertain. In particular, the degree of therapeutic nihilism in these patients, and whether it is appropriate, is unclear.

Methods: This was a prospective cohort study with a one-year follow-up.

Results: In 6,427 patients with cardiologist-diagnosed HF and angiographically proven coronary artery disease (mean age 69 years; 65% men; one-year mortality, 10%), 39% had creatinine clearances <60 ml/min. Patients with renal insufficiency were less likely to be prescribed angiotensin-converting enzyme (ACE) inhibitors, beta-blockers, statins, or aspirin (all p < 0.001). However, users of aspirin (odds ratio [OR] 0.69, 95% confidence interval [CI] 0.57 to 0.85), statins (OR 0.79, 95% CI 0.64 to 0.97), and beta-blockers (OR 0.75, 95% CI 0.62 to 0.90) were less likely to die in the subsequent 12 months than nonusers, irrespective of renal function (all OR adjusted for covariates including atherosclerotic burden and ejection fraction). Although ACE inhibitor users with creatinine clearances _60 ml/min had lower 12-month mortality (OR 0.72, 95% CI 0.48 to 0.99), ACE inhibitor users with clearances >=60 ml/min did not (OR 1.21, 95% CI 0.97 to 1.51).

Conclusions: Renal insufficiency is common in patients with HF and coronary artery disease, and these patients have more advanced coronary atherosclerosis. Patients with renal insufficiency are less likely to be prescribed efficacious therapies, but have better outcomes if they receive these medications.


Norris CM, Saunders LD, Ghali WA, Brant R, Galbraith PD, Graham M, Faris P, Dzavik V, Knudtson ML; Health-related quality of life outcomes of patients with coronary artery disease treated with cardiac surgery, percutaneous coronary intervention or medical management. Can J Cardiol. 2004 Oct 12;20(12):1259-66.

Background: Given the repeated findings of little or no difference in mortality outcomes between percutaneous coronary intervention (PCI) with or without stent and coronary artery bypass graft surgery (CABG), there is a need to assess the health-related quality of life (HRQOL) outcomes associated with revascularization decisions.

Objective: To compare risk-adjusted HRQOL outcomes by treatment strategy one year following cardiac catheterization.

Method: Using an inception cohort study design, the sample included all Alberta residents, 18 years of age or older, referred for cardiac catheterization, from January 1, 1996, to December 31, 1998, with two or more diseased coronary vessels at catheterization. Patients received a follow-up questionnaire including the Seattle Angina Questionnaire (SAQ), one year following their index catheterization. The SAQ comprises five dimensional scales measuring exertional capacity, anginal stability, anginal frequency, treatment satisfaction and quality of life.

Results: Three thousand three hundred ninety-two (78.1%) patients responded to the follow-up survey. Responders who were revascularized consistently reported significantly better HRQOL compared with responders treated with medical management. Responders undergoing CABG reported significantly better HRQOL in all but one SAQ dimension compared with responders who had either a PCI with or without stent. Responders who had a PCI with stent reported better HRQOL compared with responders who underwent a PCI without a stent.

Conclusion: The treatment decision to revascularize the coronary vessels, whether with PCI with or without a stent or with CABG, was consistently associated with significantly better HRQOL at one-year follow-up compared with patients treated with medical therapy.


Hemmelgarn BR, Southern D, Culleton BF, Mitchell LB, Knudtson ML, Ghali WA for the APPROACH Investigators. Survival after coronary revascularization among patients with kidney disease. Circulation. 2004 Oct5;110:1890-95.

Background: The optimal approach to revascularization in patients with kidney disease has not been determined. We studied survival by treatment group (CABG, percutaneous coronary intervention [PCI], or no revascularization) for patients with 3 categories of kidney function: dialysis-dependent kidney disease, non–dialysis-dependent kidney disease, and a reference group (serum creatinine _2.3 mg/dL).

Methods & Results: Data were derived from the Alberta Provincial Project for Outcomes Assessment in Coronary Heart Disease (APPROACH), which captures information on all patients undergoing cardiac catheterization in Alberta , Canada. Characteristics and patient survival in 662 dialysis patients (1.6%) and 750 non–dialysis-dependent kidney disease patients (1.8%) were compared with the remainder of the 40 374 patients (96.6%). For the reference group, the adjusted 8-year survival rates for CABG, PCI, and no revascularization (NR) were 85.5%, 80.4%, and 72.3%,respectively (P_0.001 for CABG versus NR; P_0.001 for PCI versus NR). Adjusted survival rates were 45.9% for CABG, 32.7% for PCI, and 29.7% for NR in the non dialysis kidney disease group (P_0.001 for CABG versus NR;P_0.48 for PCI versus NR) and 44.8% for CABG, 41.2% for PCI, and 30.4% for NR in the dialysis group (P_0.003for CABG versus NR; P_0.03 for PCI versus NR).

Conclusions: Compared with no revascularization, CABG was associated with better survival in all categories of kidney function. PCI was also associated with a lower risk of death than no revascularization in reference patients and dialysis-dependent kidney disease patients but not in patients with non–dialysis-dependent kidney disease. The presence of kidney disease or dependence on dialysis should not be a deterrent to revascularization, particularly with CABG.


Appoo J, Norris C, Merali S, Graham MM, Koshal A, Knudtson ML, Ghali WA. Long-term outcome of isolated coronary artery bypass surgery in patients with severe left ventricular dysfunction. Circulation. 2004 Sept14;100(11 Suppl 1):II13-7.

Background: Coronary artery bypass grafting (CABG) is indicated in patients with coronary artery disease and impaired ventricular function. However, earlier studies have suggested that prognosis of patients with severe left ventricular dysfunction is extremely poor. We used the APPROACH registry to derive contemporary estimates of prognosis associated with CABG for this high-risk patient population.

Methods & Results: The study group consisted of 7841 patients who had isolated CABG in the province of Alberta, Canada between 1996 and 2001. Patients with markedly reduced left ventricular function (ejection fraction [EF] _30%, Lo EF, n _430) were compared with those with moderate reduction in ventricular function (EF 30% to 50%, Med EF, n _2581) and those with normal left ventricular function (EF _50%, normal [Nl] EF, n_4830). The operative mortality was higher in the patient group with Lo EF (4.6%) compared with Med EF and Nl EF groups (3.4% and 1.9%, respectively, P_0.001). At 5 years, survival was 77.7% for Lo EF patients compared with 85.5% and 91.2% for Med EF and Nl EF patients, respectively (P_0.001). After controlling for other independent variables, the adjusted hazard ratio for death was 1.98 (95% CI, 1.49 to 2.62) for Lo EF relative to Nl EF. The mortality rate at 1 year was significantly lower for Lo EF patients who underwent CABG than it was for nonrevascularized Lo EF patients (risk-adjusted odds ratio, 0.36; 95% CI, 0.24 to 0.55).

Conclusions: In the modern era of cardiac surgery, CABG can be performed in Lo EF cases with an acceptable perioperative mortality risk. Our estimate of 5-year survival in this high-risk group is better than previously reported in the literature from earlier periods.


Norris CM, Ghali WA, Galbraith PD, Graham MM, Jensen LA, Knudtson ML, for the APPROACH Investigators. Women with coronary artery disease report worse health-related quality of life outcomes compared to men. Health Qual Life Outcomes. 2004 May5;2(1):21.

Background: Although there have been substantial medical advances that improve the outcomes following cardiac ischemic events, gender differences in the treatment and course of recovery for patients with coronary artery disease (CAD) continue to exist. There is a general paucity of data comparing the health related quality of life (HRQOL) in men and women undergoing treatment for CAD. The purpose of this study was to compare HRQOL outcomes of men and women in Alberta, at one-year following initial catheterization, after adjustment for known demographic, co-morbid, and disease severity predictors of outcome.

Method: The HRQOL outcome data were collected by means of a self-reported questionnaire mailed to patients on or near the one-year anniversary of their initial cardiac catheterization. Using the Seattle Angina Questionnaire (SAQ), 5 dimensions of HRQOL were measured: exertional capacity, anginal stability, anginal frequency, quality of life and treatment satisfaction. Data from the APPROACH registry were used to risk-adjust the SAQ scale scores. Two analytical strategies were used including general least squares linear modeling, and proportional odds modeling sometimes referred to as the "ordinal logistic modeling".

Results: 3392 (78.1%) patients responded to the follow-up survey. The adjusted proportional odds ratios for men relative to women (PORs > 1 = better) indicated that men reported significantly better HRQOL on all 5 SAQ dimensions as compared to women. (PORs: Exertional Capacity 3.38 (2.75–4.15), Anginal Stability 1.23 (1.03–1.47), Anginal Frequency 1.70 (1.43–2.01), Treatment Satisfaction 1.27 (1.07–1.50), and QOL 1.74 (1.48–2.04).

Conclusions: Women with CAD consistently reported worse HRQOL at one year follow-up compared to men. These findings underline the fact that conclusions based on research performed on men with CAD may not be valid for women and that more gender-related research is needed. Future studies are needed to further examine gender differences in psychosocial adjustment following treatment for CAD, as adjustment for traditional clinical variables fails to explain sex differences in health related quality of life outcomes.


Seidel JE, Ghali WA, Faris PD, Bow CJD, Waters NM, Graham MM, Galbraith PD, Mitchell LB, Knudtson ML for the APPROACH Investigators. Geographical location of residence and access to cardiac revascularization services. Can J Cardiol 2004 Apr 5; 20(5) :517-523.

Background: The centralization of health care services has numerous potential benefits but may compromise access for individuals living in remote areas.

Objectives: To examine the association between a patient’s place of residence and the likelihood of undergoing a coronary revascularization procedure within one year after cardiac catheterization.

Methods: All Alberta residents undergoing cardiac catheterization between 1995 and 1998 were examined. Geographical distance from patient place of residence to a centralized catheterization facility was calculated. The adjusted odds of undergoing cardiac revascularization within one year of catheterization was determined as a function of distance, controlling for differences in patient age, clinical factors and economic status.

Results: Of 21,816 residents who underwent cardiac catheterization in the province, 10,997 had a revascularization procedure. Graphical examination of distance revealed a change in revascularization rates in patients living more than 450 km from revascularization centres. Further analysis was conducted using this cutpoint. Patients living in these remote areas were more likely to undergo a coronary revascularization procedure within the next year (adjusted odd ratio1.65, 95%CI 1.05 to 2.59). However, these same residents were also less likely to undergo catheterization in the first place when compared with other Albertans (270 versus 398 procedures per 100,000 population).

Conclusion: Only a small proportion of the population living in Alberta’s most remote areas were more likely to undergo a revascularization procedure, indicating a remarkable uniformity of access to revascularization after coronary cardiac catheterization has occurred. This study examines the use of an existing database to gain further insights into the relationship between geography and access to cardiac care, and the distance-access relationship for coronary revascularization in Alberta.


Bow CJ, Waters NM, Faris PD, Seidel JD, Galbraith PD, Knudtson ML, Ghali WA for the APPROACH Investigators. Accuracy of city postal code coordinates as a proxy for location of residence. Int J Health Geogr 2004 Mar18; 3(1):5.

Background: Health studies sometimes rely on postal code location as a proxy for the location of residence. This study compares the postal code location to that of the street address using a database from the Alberta Provincial Project for Outcome Assessment in Coronary Heart Disease (APPROACH©). Cardiac catheterization cases in an urban Canadian City were used for calendar year 1999. We determined location in meters for both the address (using the City of Calgary Street Network File in ArcView 3.2) and postal code location (using Statistic Canada's Postal Code Conversion File).

Results: The distance between the two estimates of location for each case were measured and it was found that 87.9% of the postal code locations were within 200 meters of the true address location (straight line distances) and 96.5% were within 500 meters of the address location (straight line distances).

Conclusions: The distance between the two estimates of location for each case were measured and it was found that 87.9% of the postal code locations were within 200 meters of the true address location (straight line distances) and 96.5% were within 500 meters of the address location (straight line distances).


Faris PD, Grant FC, Galbraith PD, Gong Y, Ghali WA. Diagnostic cardiac catheterization and revascularization rates for coronary heart disease. Can J Cardiol. 2004 Mar 15;30(4):391-7.

Background: Despite evidence of regional variation across North America, there have been no comprehensive studies of cardiac procedure rates for coronary heart disease in Canada.

Objectives: To use available administrative data and a survey of catheterization facilities to examine regional and demographic variations in cardiovascular procedure rates.

Methods: A survey of all cardiac catheterization facilities in Canada was conducted, and the procedure counts from these facilities were used to determine provincial catheterization rates from 1997/1998 to 2001/2002. Procedure counts for 1997/1998 to 1999/2000 for coronary artery bypass graft (CABG) surgery and percutaneous coronary intervention (PCI) were provided by the Canadian Institute for Health Information and used to calculate revascularization procedure rates. Population projections provided by Statistics Canada were used as denominators for calculating the rates, and direct standardization was used to obtain age-and sex-adjusted rates.

Results & Conclusions: The crude rate of cardiac catheterization in Canada increased from 359.9 to 471.5 per 100,000 population across the five years studied. There was considerable variation in revascularization procedure rates across health regions and provinces. Between 1997/1998 and 1999/2000, there was little increase in the rate of CABGs performed in Canada, but a marked increase in the rate of PCIs. For both CABG and PCI, rates were higher for men than women, and highest in the 65- to 74-year-old age category. This study provides a valuable ‘snapshot’ of cardiac procedure use rates but indicates a clear need for more comprehensive collection of cardiac care data in Canada.


Westerhout CM, Saunders LD, Kaul P, Armstrong PA, Knudtson ML, Ghali WA on behalf of the APPROACH Investigators. Interinstitutional variation in the use of abciximab for percutaneous coronary intervention. Can J Cardiol 2004 Mar 15;20(4):405-410.

Background: Several clinical trials have established abciximab as an efficacious agent for use in conjunction with percutaneous coronary intervention (PCI); however, there is little documented about its use in routine clinical practice in Canada.

Objective: To determine the use of abciximab, and secondarily, its associations with one-year death and repeat revascularization rates in 2751 Alberta residents who underwent PCI in 1999.

Methods: Descriptive statistics were used to determine use patterns. Logistic regression models were used to define risk of long-term outcomes, and to determine associations between abciximab use and risk-adjusted death and repeat revascularization rates.

Results: Abciximab was administered to 43.5% of the study population, and interinstitutional differences were revealed (Site A, 46.7%; Site B, 26.6%; Site C, 54.6%, p<0.001). Use patterns according to the adjusted risk of death or repeat revascularization also differed across these sites. There were no differences between patients treated with versus those treated without abciximab in risk-adjusted one-year mortality (3.7%, 95% confidence interval [CI] 2.8% to 3.7% versus 3.1%, 95% CI 2.3% to 4.0%) or revascularization rates (16.7%, 95%CI 14.8 to 19.1% vs. 15.8%, 95%CI 14.0 to 17.7%). However, differences in baseline clinical characteristics between these two groups may limit the inferences that can be made from these outcome comparisons.

Conclusions: Use patterns varied across the tertiary care hospitals in Alberta and the use of abciximab was not associated with reduced rates of long-term death or repeat revascularization. The absence of provincial or national guidelines may have influenced the uptake and application of this novel therapy.


King KM, Ghali WA, Faris PD, Curtis MJ, Galbraith PD, Graham MM, Knudtson ML. Sex differences in outcomes after cardiac catheterization: effect modification by treatment strategy and time. JAMA. 2004 Mar 10;291(10):1220-5.

Context: Studies comparing outcomes of cardiac care in women vs men yield various results, with some suggesting worse outcomes for women and others suggesting equivalent outcomes.

Objective: To determine whether extent of coronary disease, treatment strategy, and follow-up time influence the risk of death in women vs men among patients who have had cardiac catheterization.

Design, Setting, and Patients: We studied a large inception cohort by using detailed clinical data from a registry of 37401 patients undergoing cardiac catheterization in Alberta, Canada, from 1995-2000, with follow-up through December 31, 2001.

Main Outcome Measures: The risk of death for women vs men was assessed for all patients combined and then in analyses stratified by degree of coronary anatomic risk and by treatment strategy (no revascularization, percutaneous coronary intervention [PCI], coronary artery bypass graft [CABG] surgery). The latter analysis included a graphic assessment of the changing relative risk over time for women vs men.

Results: Women had higher 1-year mortality than men did (5.6% vs 4.6%; P<.001). However, stratified analyses demonstrated that sex differences in risk occurred only yearly after catheterization and were most apparent among patients undergoing revascularization. The early risk-adjusted relative risks for women vs men were elevated at 3.49 (95% confidence interval [CI], 1.95-6.24) for CABG surgery and 2.38 (95% CI, 1.48-3.83) for PCI on day 1 after catheterization, with a subsequent decrease in relative risk over time to equivalence in risk between sexes before 1 year.

Conclusions: Sex-based differences in death rates after cardiac catheterization are time- and treatment-specific. This finding may at least partially explain the discrepancies in results from earlier studies on sex differences in outcomes of cardiac care.


Norris CM, Ghali WA, Saunders LD, Brant R, Galbraith PD. Systematic review of statistical methods used to analyze Seattle Angina Questionnaire scores. Can J Cardiol 2004 Feb2; 20(2):187-193.

Background:The Seattle Angina Questionnaire (SAQ) is being used with increasing frequency in clinical research to address the health-related quality of life (HRQOL) outcomes of patients with coronary artery disease. The reliability and validity of the SAQ as a disease-specific HRQOL questionnaire has been established. The purpose of this paper was to systematically identify all studies analyzing SAQ scores, and to review the suitability of the statistical methods used.

Methods: The literature search included all years from the development of the SAQ (1994) to December 2001. Electronic databases were searched using ‘ Seattle angina questionnaire’ as a key word, text word or medical subject heading, as well as combinations of Seattle, angina and questionnaire. The Scientific Citation Index was searched to identify any manuscripts that cited the developmental articles of the SAQ. Relevant manuscripts were identified as studies that used the SAQ as a measurement tool for HRQOL outcome data.

Results: Of the 62 studies identified, 14 articles used the SAQ as an outcome measurement tool. The statistical validity of all but one of the 14 studies was doubtful because assumptions required for the use of parametric tests were not addressed and there was no mention of the distributions of the SAQ scores. Based on the designs of the studies, unsuitable analysis methods were used.

Conclusions: Our results demonstrate that investigators may need to increase their attention to the distributional characteristics of their HRQOL data and the design of the study before applying statistical tests to appropriately analyze SAQ HRQOL data.


Graham MM, Ghali WA, Faris PD, Galbraith PD, Norris CM, Knudtson ML for the APPROACH Investigators. Sex differences in the prognostic importance of diabetes in patients with ischemic heart disease undergoing coronary angiography. Diabetes Care. 2003 Nov;26(11):3142-7.

Objective: Women with ischemic heart disease have poorer outcomes than men and are suggested to have greater risk associated with diabetes. We evaluated the prognosis associated with diabetes, in analyses stratified by sex, to determine whether similar differences are seen in a large unselected cohort of patients.

Research Design & Methods:Using the Alberta Provincial Project for Outcomes Assessment in Coronary Heart Disease (APPROACH), a clinical data collection and follow-up initiative capturing all patients undergoing cardiac catheterization in Alberta, Canada, the relative significance of diabetes on long-term survival in 13,152 men and 4,249 women was evaluated in patients presenting with or without myocardial infarction and according to first treatment received.

Results: The 1-year mortality rates were 4.7% and 6.8% in men and women ( P <0.001), 4.1% and 7.4% in nondiabetic and diabetic men ( P <0.001), and 5.8% and 9.6% in nondiabetic and diabetic women, respectively ( P <0.001). The risk-adjusted Cox proportional hazard ratios associated with diabetes in myocardial infarction were 1.03 in men and 1.20 in women. The diabetes hazard ratios for percutaneous coronary intervention were 1.28 in men and 1.40 in women, 1.23 in men and 1.32 in women for bypass surgery, and 1.26 in men and 1.31 in women for medical therapy ( P =NS for all diabetes hazard ratio comparisons between men and women).

Conclusions: Hazard ratios quantifying the adverse prognosis associated with diabetes in patients undergoing angiography are consistently higher among women than men, but the differences across sexes are not statistically significant. These slight sex differences noted in the APPROACH registry are similar to previously reported findings and may be clinically important.


Faris PD, Ghali WA, Brant R. Bias in estimates of confidence intervals for health outcome report cards. Journal of Clinical Epidemiology 2003 Jun;56:553-8.

Health researchers commonly use logistic regression when profiling health providers. Data from the patients treated by the providers are used to construct models predicting the expected number of outcomes for providers and the ratio of observed to expected outcomes (O/E ratio) used as a risk-adjusted measure of provider performance. Typically, when calculating the standard deviation (SD) of O/E ratios, only O is treated as a random variable. We used the propagation of errors (Pe) to derive a SD estimate that accounted for variability in O and the estimate of E. Using data previously used to profile Canadian cardiac surgery providers, we compared Pe-SD estimates with typical SD (SDT) estimates. The SDT estimates and confidence intervals were always larger than the Pe estimates, most notably when one or more providers treated a large proportion of the patients. This was confirmed using computer simulations. SDT estimates should be abandoned in favor of more sophisticated estimates.


Southern DA, Ghali WA, Faris PD, Norris CM, Galbraith PD, Graham MM, Knudtson ML for the APPROACH Investigators. Misclassification of income quintiles derived from area-based measures: a comparison of enumeration area and forward sortation area. Can J Public Health 2002 Nov/Dec; 93(6):465-469.

Background: Census-based methods are often used to estimate socioeconomic status. We assessed the agreement between Forward Sortation Area (FSA) and Enumeration Area (EA) derived income levels for all patients undergoing cardiac catheterization in Alberta, Canada, from 1995-1998.

Methods: Income quintiles were calculated from census data for FSA and EA level. FSA and EA-derived income measures were compared for misclassification. Both methods were then applied to the data to determine 4-year survival by income grouping in 21,446 patients following catheterization.

Results: The variability in EA-derived incomes for any given FSA-derived income is large. Only 40% of income quintiles are in agreement between the methods. For EA-based analyses, there is a linear relationship between higher income and lower mortality across all quintiles, while for FSA-based analyses, only the lowest in come quintile had significantly higher mortality.

Discussion: Assuming that FSA-based methods are more likely to misclassify income compared to EA-based measures, the results for the FSA-based analyses are more likely to be erroneous. EA-derived measures should therefore be used when individual data are not available.


Graham MM, Ghali WA, Faris PD, Galbraith PD, Norris CM and Merril Knudtson for the APPROACH Investigators. Survival after coronary revascularization in the elderly. Circulation 2002 May21;105(20):2378-84

Background: Elderly patients with ischemic heart disease are increasingly referred for coronary artery bypass grafting (CABG) or percutaneous coronary intervention (PCI). However, reports of poor outcomes in the elderly have led to questions about the benefit of these strategies. We studied survival by prescribed treatment (CABG, PCI, or medical therapy) for patients in 3 age categories: <70 years, 70 to 79 years, and>=80 years of age.

Methods and Results: The Alberta Provincial Project for Outcomes Assessment in Coronary Heart Disease (APPROACH) is a clinical data collection and outcome monitoring initiative capturing all patients undergoing cardiac catheterization and revascularization in the province of Alberta, Canada, since 1995. Characteristics and long-term outcomes of a cohort of >6000 elderly patients with ischemic heart disease were compared with younger patients. In 15 392 patients >70 years of age, 4-year adjusted actuarial survival rates for CABG, PCI, and medical therapy were 95.0%, 93.8%, and 90.5%, respectively. In 5198 patients 70 to 79 years of age, survival rates were 87.3%, 83.9%, and 79.1%, respectively. In 983 patients >=80 years of age, survival was 77.4% for CABG, 71.6% for PCI, and 60.3% for medical therapy. Absolute risk differences in comparison to medical therapy for CABG (17.0%) and PCI (11.3%) were greater for patients >=80 years of age than for younger patients.

Conclusions: Elderly patients paradoxically have greater absolute risk reductions associated with surgical or percutaneous revascularization than do younger patients. The combination of these results with a recent randomized trial suggests that the benefits of aggressive revascularization therapies may extend to subsets of patients in older age groups.


Ghali WA, Faris PD, Galbraith PD, Norris CM, Curtis MJ, Saunders LD, Dzavik V, Mitchell LB, Knudtson ML. Sex differences in access to coronary revascularization after cardiac catheterization: importance of detailed clinical data. Ann Intern Med 2002 May21;136(10):723-32.

Background: Although some studies suggest that access to cardiac procedures may differ by sex, others have found no evidence of gender bias in cardiac care.

Objective: To study rates of percutaneous coronary intervention (PCI) or coronary artery bypass graft (CABG) surgery in men and women after cardiac catheterization.

Design: Cohort study with prospective data collection.

Setting: Alberta, Canada.

Patients: Persons undergoing cardiac catheterization between 1 January 1995 and 31 December 1998 (n_ 21 816).

Measurements: The occurrence of revascularization procedures (PCI or CABG) in the year after cardiac catheterization was measured. Unadjusted revascularization rates, partially adjusted rates (adjusted for clinical variables available in most databases, including administrative databases), and fully adjusted rates (additionally adjusted for extent of coronary artery disease and ejection fraction) were also evaluated.

Results: The unadjusted relative risk was 0.67 (95% CI, 0.65 to 0.71) for the end point of any revascularization in women relative to men. The relative risk increased to 0.69 (CI, 0.66 to 0.72) with partial adjustment and to 0.98 (CI, 0.94 to 1.03) with full adjustment, indicating equivalent access to revascularization for men and women. For PCI, the corresponding relative risks were 0.77 (CI, 0.73 to 0.82), 0.84 (CI, 0.80 to 0.89), and 1.02 (CI, 0.96 to 1.08). For CABG surgery, the relative risks were 0.54 (CI, 0.51 to 0.58), 0.51 (CI, 0.48 to 0.55), and 0.93 (CI, 0.87 to 1.01).

Conclusions: In Alberta, Canada, clinical variables fully explain sex differences in rates of revascularization after cardiac catheterization, and misleading conclusions would arise without full adjustment for clinical differences between men and women. Extreme caution is needed in interpreting reports on access to care that use sparsely detailed clinical data sources.


Faris PD, Ghali WA, Brant R, Norris CM, Galbraith PD, Knudtson ML for the APPROACH Investigators. Multiple imputation versus data enhancement for dealing with missing data in observational health care outcome analyses. J Clin Epidem 2002 Feb;55(2):184-191.

The problem of missing data is frequently encountered in observational studies. We compared approaches to dealing with missing data. Three multiple imputation methods were compared with a method of enhancing a clinical database through merging with administrative data. The clinical database used for comparison contained information collected from 6,065 cardiac care patients in 1995 in the province of Alberta, Canada. The effectiveness of the different strategies was evaluated using measures of discrimination and goodness of fit for the 1995 data. The strategies were further evaluated by examining how well the models predicted outcomes in data collected from patients in 1996. In general, the different methods produced similar results, with one of the multiple imputation methods demonstrating a slight advantage. It is concluded that the choice of missing data strategy should be guided by statistical expertise and data resources.


Quan H, Ghali WA, Verhoef MJ, Norris CM, Galbraith PD, and Knudtson ML. Use of chelation therapy after coronary angiography. Am J Med 2001 Dec15;111(9):686-691.

Purpose: Among patients who had undergone coronary angiography, we sought to determine the proportion of chelation therapy users, their sociodemographic and clinical characteristics, and the association of chelation therapy with subsequent revascularization.

Methods: We studied all patients who underwent coronary angiography in the province of Alberta, Canada, during 1995 and 1996. The cohort was followed for up to 6 years to determine subsequent revascularization status. Use of chelation therapy was determined by a mailed survey 1 year after angiography.

Results: Among the 5854 patients who responded to the mail survey (70% response rate), 210 (3.6%) reported current use of chelation therapy and 252 (4.3%) reported past use. Current use of chelation therapy was associated with extensive coronary artery disease (adjusted odds ratio [OR]=3.3; 95% confidence interval [CI]: 1.9 to 5.7 for 3-vessel disease; and OR = 2.7; 95% CI: 1.2 to 6.0 for left main disease, as compared with those with normal anatomy) and the absence of diabetes (OR= 0.6; 95% CI: 0.4 to 0.9). Current users were less likely to have undergone percutaneous transluminal coronary angioplasty (OR=0.7; 95% CI: 0.5 to 0.9) and coronary artery bypass graft (CABG) surgery (OR = 0.3; 95% CI: 0.2 to 0.5) in the first year after angiography, but were as likely as nonusers of chelation therapy to have undergone CABG surgery in the subsequent 3-to 5-year period (adjusted hazard ratio [HR]=1.1; 95% CI: 0.7 to 1.9). Past use of chelation therapy was associated with a history of CABG surgery before coronary angiography (OR=1.6; 95% CI: 1.1 to 2.3) and extensive coronary artery disease. Past users were also more likely to have undergone CABG surgery in the follow-up period (HR = 1.7; 95% CI: 1.1 to 2.6).

Conclusions: About 8% of patients who underwent cardiac catheterization for coronary artery disease were using or had previously tried chelation therapy. Users may have foregone revascularization in favor of this less invasive yet unproven treatment, with some users subsequently undergoing conventional treatment after chelation. Alternatively, some patients may have turned to chelation as a “last resort” after having been judged unsuitable for revascularization.


Ghali WA, Quan H, Brant R, van Melle G, Norris CM, Faris PD and Knudtson ML for the APPROACH Investigators. A comparison of two methods for calculating adjusted survival curves from proportional hazards models. JAMA 2001 Sept26;286(12):1494-97.

Context: Adjusted survival curves are often presented in medical research articles. The most commonly used method for calculating such curves is the mean of covariates method, in which average values of covariates are entered into a proportional hazards regression equation. Use of this method is widespread despite published concerns regarding the validity of resulting curves.

Objective: To compare the mean of covariates method to the less widely used corrected group prognosis method in an analysis evaluating survival in patients with and without diabetes. In the latter method, a survival curve is calculated for each level of covariates, after which an average survival curve is calculated as a weighted average of the survival curves for each level of covariates.

Design, Setting, and Patients: Analysis of cohort study data from 11,468 Alberta residents undergoing cardiac catheterization between January 1, 1995 and December 31, 1996.

Main Outcome Measures: Crude and risk-adjusted survival for up to 3 years after cardiac catheterization in patients with vs without diabetes, analyzed by the mean of covariates method vs the corrected group prognosis method.

Results: According to the mean of covariates method, adjusted survival at 1044 days was 94.1% and 94.9% for patients with and without diabetes, respectively, with misleading adjusted survival curves that fell above the unadjusted curves. With the corrected group prognosis method, the corresponding survival values were 91.3% and 92.4%, with curves that fell more appropriately between the unadjusted curves.

Conclusions:Misleading adjusted survival curves resulted from using the mean of covariates method of analysis for our data. We recommend using the corrected group prognosis method for calculating risk-adjusted curves.


Graham MM, Faris PD, Ghali WA, Galbraith PD, Norris CM, Badry JT, Mitchell LB, Curtis MJ and Knudtson ML for the APPROACH Investigators. Validation of three myocardial jeopardy scores in a population-based cardiac catheterization cohort. Am Heart J 2001 Aug; 142(2):254-61.

Background: The Jeopardy Score from Duke University and the Myocardial Jeopardy Index from the Bypass Angioplasty Revascularization Investigation (BARI) have been validated but never applied to a large unselected cohort. We assessed the prognostic value of these existing jeopardy scores, along with that of a new Lesion Score developed for the Alberta Provincial Project for Outcome Assessment in Coronary Heart Disease (APPROACH), a clinical data collection initiative capturing all patients undergoing cardiac catheterization in the province of Alberta.

Methods: The predictive value of these three scores were compared in a cohort of >20,000 patients (9922 treated medically, 6334 treated with percutaneous intervention, and 3811 treated with bypass surgery). Scores were considered individually in logistic regression models for their ability to predict outcome and then added to models containing sociodemographic data, comorbidities, ejection fraction, indication for procedure, and descriptors of coronary anatomy.

Results: All scores were found to be predictive of 1-year mortality, especially when patients are treated medically or with percutaneous intervention. In these patients, the APPROACH Lesion Score performed slightly better than the other jeopardy scores. The Duke Jeopardy Score was most predictive in those patients undergoing coronary bypass surgery.


Myocardial jeopardy scores provide independent prognostic information for patients with ischemic heart disease, especially if those patients are treated medically or with percutaneous intervention. These scores represent potentially valuable tools in cardiovascular outcome studies. The APPROACH Lesion Score may perform slightly better than previously developed jeopardy scores.



Dzavik V, Ghali WA, Norris CM, Mitchell B, Koshal A, Saunders DL, Galbraith PD, Hui W, Faris PD, Knudtson ML for the APPROACH Investigators. Long-term survival in 11,661 patients with multivessel disease coronary artery disease in an era of stenting: A report from APPROACH. Am Heart J 2001 Jul; 142(1):119-26.

Background: Studies of survival of patients with multivessel coronary artery disease (MVD) in the prestent era suggested that outcomes after coronary artery bypass surgery (CABG) are similar to those after percutaneous coronary intervention (PCI) in subsets of coronary severity. The purpose of this study of the Alberta Provincial Project for Outcome Assessment in Coronary Heart Disease (APPROACH) was to examine the association between treatment and survival up to 5 years in patients with MVD enrolled from 1995 through 1998.

Methods and Results: Data on patient characteristics were obtained at the time of the initial coronary angiography. Survival was determined through data linkage to the provincial Bureau of Vital Statistics. Risk-adjusted hazard ratios were calculated to compare different treatments. In the 11,661 patients with MVD, CABG was the initial therapy in 3782, PCI in 3540, and medical therapy in 4339. Cumulative 5-year survival was 91.4% with CABG, 91.9% with PCI, and 82.9% with medical therapy (P < .001). Hazard ratios were CABG: medical 0.53 (95% confidence interval [CI] 0.46-0.71), PCI: medical 0.65 (95% CI 0.56-0.74), and CABG: PCI 0.81 (95% CI 0.68-0.96). Analysis across coronary severity groups revealed a benefit of CABG compared with PCI only in the group with severe left main CAD: 0.30 (95% CI 0.17-0.54).

Conclusions: In a multicenter clinical setting, MVD patients treated with revascularization have significantly higher 5-year survival rate than do those treated medically. Risk-adjusted comparison reveals PCI treatment to be associated with long-term survival similar to treatment with CABG in all coronary severity subgroups except the group with severe left main coronary artery disease. Patient selection factors are likely to be contributing to these findings.


Hemmelgarn BR, Ghali WA, Quan H, Brant R, Norris CM, Taub KJ, Knudtson ML. Poor long term survival after coronary angiography in patients with renal insufficiency. Am J Kidney Dis 2001 Jan;37(1):64-72.

Cardiovascular disease is common among dialysis patients, but much less is known regarding non–dialysis dependent renal insufficiency (NDDRI) and its association with cardiac disease. We undertook a study to assess the impact of renal insufficiency on survival post–coronary angiography by comparing three groups of patients: dialysis-dependent patients, patients with NDDRI (creatinine > 2.3 mg/dL), and a reference group with creatinine levels less than 2.3 mg/dL and not on dialysis therapy. We used a prospective cohort that consisted of all patients undergoing coronary angiography in Alberta, Canada, from January 1, 1995, to December 31, 1997. Of the 16,989 patients, 196 patients (1.2%) were on dialysis therapy, 262 patients (1.5%) had NDDRI, and 16,531 patients (97.3%) formed the reference group. Mortality rates 1 year after angiography were 30.2% for patients with NDDRI, 15.8% for dialysis patients, and 4.1% for the reference group. Compared with the reference group, crude 4-year survival was significantly worse for dialysis patients and those with NDDRI, with hazard ratios of 4.05 (95% confidence interval, 3.02 to 5.42) and 7.32 (95% confidence interval, 5.97 to 8.97), respectively. Even after adjusting for clinical risk factors, survival remained worse for dialysis patients and those with NDDRI, with hazard ratios of 2.59 (95% confidence interval, 1.92 to 3.49) and 2.51 (95% confidence interval, 2.02 to 3.12), respectively. We conclude that renal insufficiency, both dialysis dependent and non–dialysis dependent, is an independent risk factor for increased mortality and poor long-term survival among patients undergoing coronary angiography.


Ghali WA, Quan H, Norris CM, Dzavik V, Naylor CD, Mitchel LB, Brant R, Knudtson ML. Prognostic significance of diabetes as a predictor of survival after cardiac catheterization. Am J Med 2000 Nov;109(7):543-8.

Purpose: Diabetes is a recognized risk factor for the development of cardiac disease, but its importance as a prognostic factor among patients with known cardiovascular disease is less clear. We evaluated survival in patients with and without diabetes who underwent cardiac catheterization for presumed coronary artery disease.

Subject and Methods: We analyzed data from a prospective cohort study that captures detailed clinical information and longitudinal outcomes for all patients who undergo cardiac catheterization in Alberta, Canada. We studied 11,468 patients, 1959 (17%) of whom had diabetes. Logistic regression was used to model predictors of 1-year mortality, and proportional hazards analysis was used to model predictors of survival up to 3 years after cardiac catheterization.

Results: One-year mortality was 7.6% for patients with diabetes versus 4.1% for those without diabetes (odds ratio 5 1.9, 95% confidence interval [CI]: 1.6 to 2.3). After adjusting for other characteristics of the patients, including comorbid conditions, previous cardiac history, coronary anatomy, and renal function, the odds ratio for 1-year mortality was 1.1 (95% CI: 0.8 to 1.3). Similarly, the adjusted hazard ratio for longer term mortality was 1.2 (95% CI: 1.0 to 1.4, mean follow-up of 702 days).

Conclusions: These results suggest that there is little or no independent association between diabetes and mortality for up to 3 years after cardiac catheterization. Estimates of short- to intermediate-term prognosis for diabetic patients with coronary artery disease should be based on the presence of other prognostic factors associated with diabetes.


Ghali WA, Knudtson ML for the APPROACH Investigators. Overview of 'APPROACH' the Alberta provincial project for outcome assessment in coronary heart disease. Can J Cardiol 2000 Oct10; 16(10):1225-1230.

The Alberta Provincial Project for Outcome Assessment in Coronary Heart Disease (APPROACH) is an ongoing prospective data collection initiative that began in January 1995. The cohort for the initiative is all patients undergoing cardiac catheterization in Alberta. Patients are followed longitudinally for the determination of short and long term clinical, economic and quality of life outcomes. The project is producing valuable information on the processes and outcomes of cardiac care in Alberta, and is now being implemented in British Columbia as well. This paper provides an overview of APPROACH with specific attention to the project’s general objectives, salient features, database structure and technical specifications. Examples of applied research projects based on APPROACH data are also provided.


Norris CM, Ghali WA, Knudtson ML, Saunders LD, Naylor CD. Dealing with missing data in observational health care outcome analysis. J Clin Epidemiol. 2000 Apr;53:377-383.

Observational outcome analyses appear frequently in the health research literature. For such analyses, clinical registries are preferred to administrative databases. Missing data are a common problem in any clinical registry, and pose a threat to the validity of observational outcomes analyses. Faced with missing data in a new clinical registry, we compared three possible responses: exclude cases with missing data; assume that the missing data indicated absence of risk; or merge the clinical database with an existing administrative database. The predictive model derived using the merged data showed a higher C statistic (C= 0.770), better model goodness-of-fit as measured in a decile-of-risk analysis, the largest gradient of risk across deciles (46.3), and the largest decrease in deviance (-2 log likelihood =406.2). The superior performance of the enhanced data model supports the use of this “enhancement” methodology and bears consideration when researchers are faced with nonrandom missing data.