Use of time-dependent measures to estimate benefits of β-blockers after myocardial infarction

Purpose To estimate the reduction in all-cause mortality conferred by beta-blockers in a population-based cohort of elderly survivors of myocardial infarction during the year following hospital discharge. Methods A dynamic retrospective cohort was assembled from persons aged 66 years and over surviving myocardial infarction in Quebec between 1990 and 1993. Information on hospitalizations was linked to medication and physician claims, demographic characteristics and vital status. Subjects prescribed beta-blockers at hospital discharge had fewer comorbid medical conditions, less pre-existing cardiovascular disease and less severe infarcts. To control for these differences, analyzes were restricted to subjects receiving at least one beta-blocker and mortality was compared between periods with and without beta-blocker exposure using Cox proportional hazard models. Results Among 14547 survivors of myocardial infarction, 41% were dispensed at least one beta-blocker. Among those subjects, the risk of dying during periods of beta-blocker use was reduced 40% (hazard ratio= 0.6; 95% CI: 0.5, 0.7). Conclusion Confounding by indication threatens the validity of observational studies of intended effects of medications. For elderly survivors of myocardial infarction, the estimated benefit of beta-blockers from observational studies is greater than the estimate from randomized trials. Greater benefits do not seem to be an artifact arising from systematically prescribing beta-blockers to subjects with better prognosis. Reducing confounding by indication can enhance the validity of observational studies of medications and widen research applications of administrative health databases. While the actual benefits of medications are never truly known these studies can provide a credible range that brackets the truth. Copyright (C) 2004 John Wiley Sons, Ltd.