Meta-analysis of morbidity and mortality in five exercise capacity trials evaluating ramipril in chronic congestive cardiac failure

In 5 separate exercise capacity trials in similar patients with chronic congestive heart failure performed in Europe, the United States, and South Africa, 627 patients were randomized to ramipril and 428 to placebo. The dose of ramipril ranged from 1.25 to 20 mg/day. Follow-up was at 12 or 24 weeks. None of the trials were designed to assess efficacy with regard to clinical out-come. To assess in the combined experience whether there was an effect of ramipril on mortality, hospitalization, functional classification (New York Heart Association class), and exercise capacity, we pooled data from each trial and performed a meta-analysis. Of the patients randomized to ramipril and placebo, respectively, and based on intention to treat, 14 (2.2%) and 18 (3.8%) patients died (odds ratio 0.60, 95% confidence interval 0.28 to 1.29), and 59 (9.4%) and 67 (14.3%) patients died or were hospitalized (odds ratio 0.68, 95% confidence interval 0.46 to 1.00). The New York Heart Association class improved in 29% and 25%, respectively, whereas 8% and 15% deteriorated (p = 0.04, based on intention to treat; death and hospitalization considered as deterioration). In ranked comparisons based on intention to treat and with imputation of exercise time as 0 for patients who were unable to exercise because of death or who were hospitalized, exercise capacity was significantly improved by ramipril. We conclude that ramipril is likely to have an effect on mortality, morbidity, and functional capacity in patients with chronic congestive heart failure similar to that of other angiotensin-converting enzyme inhibitors.