Effects of early and late administration of angiotensin-converting enzyme inhibitors on mortality after myocardial infarction

Background Clinical trials demonstrating that angiotensin-converting enzyme (ACE) inhibitors reduce mortality when prescribed following myocardial infarction have focused on either early or late administration. It is unclear what the overall mortality benefits are and how long they last. Methods We identified trials of ACE inhibitor therapy after myocardial infarction that were published between 1987 and 2002. Studies were included if they were randomized placebo-controlled trials with follow-up of at least 1 month. Separate analyses were performed for trials of therapy initiated within 48 hours of infarction (early administration) or initiated more than 48 hours after infarction (late administration). The Yusuf-Peto modification of the Mantel-Haenszel method was used to obtain summary odds ratios for mortality. Results Twenty-two trials (14 early administration, 8 late administration) met the inclusion criteria. Early administration of ACE inhibitors was associated with a slight reduction in 1-month mortality (odds ratio [OR] = 0.93; 95% confidence interval [CI]: 0.88 to 0.97) and a much larger reduction in 1-year mortality (OR = 0.68; 95% CI: 0.54 to 0.87). Late therapy was associated with significant reductions in 1-year mortality (OR = 0.84; 95% CI: 0.73 to 0.97), 2-year mortality (OR = 0.75; 95% CI: 0.67 to 0.85), and 3-year mortality (OR = 0.74; 95% CI: 0.65 to 0.84). Conclusion Both early and late administration of ACE inhibitor therapy are associated with lower mortality following myocardial infarction, with the largest benefits observed with long-term mortality.