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Effect of different angiotensin-converting-enzyme inhibitors on mortality among elderly patients with congestive heart failure

From the Division of Internal Medicine and Epidemiology (Pilote, Abrahamowicz, Behlouli), Montreal General Hospital, Montréal, Que.; the Department of Epidemiology, Biostatistics and Occupational Health (Abrahamowicz), McGill University, Montréal, Que.; the Divisions of Epidemiology and Cardiology (Eisenberg), Sir Mortimer B. Davis–Jewish General Hospital, Montréal, Que.; the Division of Cardiology, University of British Columbia, and the Centre for Health Evaluation and Outcome Sciences (Humphries), Vancouver, BC; and the Institute for Clinical Evaluative Sciences (Tu), Sunnybrook Health Sciences Centre, Toronto Ont.

Correspondence to: Dr. Louise Pilote, Divisions of Internal Medicine and of Clinical Epidemiology, McGill University Health Centre, 687 Pine Ave. W, V Building, Montréal QC H3A 1A1; fax 514 934-8293; louise.pilote{at}mcgill.ca

Background: Existing clinical trial data do not address whether all angiotensin-converting-enzyme (ACE) inhibitors are similarly beneficial in improving survival and reducing the rate of readmission among patients with congestive heart failure. We sought to answer this question using administrative databases from Canada's 3 most populous provinces.

Methods: Using linked hospital discharge and prescription claims databases in Quebec, Ontario and British Columbia, we identified all patients 65 years or older who were admitted to hospital because of congestive heart failure between Jan. 1, 1998, and Mar. 31, 2002, and who had not been admitted for the same reason in the 3 years preceding the study period. We analyzed the association between the type of ACE inhibitor prescribed within 30 days after discharge and subsequent mortality using Cox proportional hazards models. We then adjusted for demographic, clinical, physician and hospital-related variables, with additional time-dependent variables representing current drug use and dosage. We chose ramipril as the reference category for comparison with the other ACE inhibitors because it has increasingly been prescribed to patients with congestive heart failure.

Results: A total of 43 316 patients with congestive heart failure filled prescriptions for ACE inhibitors within 30 days after discharge from hospital. Demographic, clinical and prescription-related characteristics were similar among users of each type of ACE inhibitor. In the time-dependent model, the mortality associated with 5 ACE inhibitors was similar to that with ramipril: adjusted hazard ratios (and 95% confidence intervals [CIs]) were 0.95 (0.89–1.02) for lisinopril, 0.92 (0.85–1.00) for fosinopril, 0.99 (0.88–1.11) for quinapril, 0.90 (0.77–1.06) for perindopril and 1.00 (0.80–1.24) for cilazapril. However, use of enalapril or captopril was associated with higher mortality compared with ramipril: adjusted hazard ratios (and 95% CIs) were 1.10 (1.04–1.16) for enalapril and 1.13 (1.01–1.26) for captopril.

Interpretation: When prescribing ACE inhibitors to patients, physicians should consider a possible 10%–15% increase in mortality with captopril and enalapril compared with ramipril among patients with congestive heart failure.

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