My commentary1 elicited several letters supporting the results of the HOPE study. However, it was not my intention to belittle the importance of the trial; rather, I wanted to put into perspective the dramatic rise in prescribing rates for ramipril that occurred in Canada around the time the study findings were published.2
HOPE was a well-conducted and timely clinical trial, and certainly part of the response in ramipril prescribing rates was appropriate. However, HOPE did not address the use of ramipril immediately after acute myocardial infarction or in patients with congestive heart failure. Yet, as illustrated by Tu and associates,3 Canadian physicians almost immediately began using ramipril in these subgroups, presumably because of an assumption of a class effect among ACE inhibitors.
Salim Yusuf and Gilles Dagenais quote independent analyses of the cost-effectiveness of ramipril. These latter studies were published months to years after publication of the HOPE trial, but the use of ramipril increased sharply at the time of and even before publication of the trial. Yusuf and Dagenais also suggest that Canadian cardiologists and internists became familiar with ramipril because of their involvement in the study. The fact that prescriptions of ramipril increased even before the trial was published and well before the subgroup and cost-effectiveness analyses appeared suggests that physicians began using ramipril for reasons other than the evidence available at the time.
David Fitchett refers to the AIRE study, which was published in 1993.4 In that study, ramipril was given “late,” more than 48 hours after acute myocardial infarction in patients with evidence of congestive heart failure. In fact, none of the trials that examined the early administration of ACE inhibitors used ramipril. Fitchett suggests that we should assume a class effect for ACE inhibitors, but what is the evidence for this assumption? The recent withdrawal of cerivastatin from the market should serve as a reminder that the drugs within a class may not all have the same benefits and side effects.
Wally Shishkov's concerns about the use of medication to prevent type 2 diabetes mellitus are warranted. Basic lifestyle modifications should be attempted before drug therapy is implemented. Ronald Sigal argues that diabetic patients should be given ramipril on the basis of the HOPE results. I agree, and I do prescribe ramipril for my diabetic patients. The intent of my editorial was to caution physicians against extending the HOPE results to populations not represented by patients in the study.
Finally, if the explanation for the sharp rise in ramipril use is entirely evidence based, why is this remarkable growth in sales almost entirely a Canadian phenomenon? Between 1999 and 2002, the market share of ramipril among ACE inhibitors and angiotensin receptor blockers quadrupled in Canada (from 8% to 31%),5 while the market share in the United States rose only slightly (from 3% to 6%).6
Louise Pilote Division of Clinical Epidemiology McGill University Montréal, Que.