Clinical trial evidence has been accumulating to support the benefits of ramipril in a wide range of clinical applications. Yet Louise Pilote, in a recent commentary,1 states that in most trials of angiotensin-converting enzyme (ACE) inhibitor therapy for patients with congestive heart failure, acute myocardial infarction or diabetes mellitus, ramipril was not the main ACE inhibitor studied.
Ramipril is the only ACE inhibitor shown to be beneficial in the prevention of adverse cardiovascular outcomes in diabetic patients with one risk factor for vascular disease. The Micro-HOPE study2 showed that ramipril given for 4 to 5 years reduced cardiovascular mortality by 37% (relative risk 0.63, 95% confidence interval [CI] 0.49 to 0.79, p = 0.0001) among the 3657 diabetic patients enrolled in the HOPE study.3
Pilote goes on to report that of the 100 000 patients enrolled in trials of early administration of ACE inhibitors after acute myocardial infarction, none were assigned to receive ramipril. However, in the Acute Infarction Ramipril Efficacy (AIRE) study,4 2006 patients were randomly assigned to receive ramipril or placebo 3 to 10 days after acute myocardial infarction complicated by heart failure. After an average 15-month treatment period, there was an absolute risk reduction of 6% and a relative risk reduction of 27% for all-cause mortality (95% CI 11% to 40%, p = 0.002).
Pilote is correct in stating that only about 17% of patients in a clinical trial of ACE inhibitors were randomly assigned to receive ramipril.5 However, there is substantial evidence supporting the use of ramipril for the prevention of heart failure from both the AIRE trial4 and the HOPE study.6 Furthermore, it is likely that the benefit of ACE inhibition in the management of heart failure is a class effect.
The large increase in the sales of ramipril after publication of the HOPE study was driven by an excellent medical education campaign supported by a powerful landmark clinical trial. Is it not possible that application of the results of the HOPE trial in diabetic patients and in patients with vascular disease has saved many lives and that it has prevented numerous myocardial infarctions and strokes?
David Fitchett Terence Donnelly Heart Centre St. Michael's Hospital Toronto, Ont.