The striking effect of the Heart Outcomes Prevention Evaluation (HOPE) on ramipril prescribing in Ontario

Background — The Heart Outcomes Prevention Evaluation (HOPE), a Canadian-led, multicentre, randomized controlled trial, demonstrated the effectiveness of the ACE inhibitor ramipril in the secondary prevention of cardiovascular disease in patients who were at high risk for cardiovascular events but did not have left ventricular dysfunction or heart failure. We studied whether HOPE affected the prescribing of ACE inhibitors generally, and ramipril specifically, in Ontario, where the trial was coordinated.

Methods — We used linked administrative databases to examine prescribing patterns for ACE inhibitors in the 1.29 million to 1.54 million elderly (aged 66 and over) residents of Ontario during the study period and specifically those with diabetes or congestive heart failure. For all new prescriptions for these drugs filled between Jan. 1, 1993, and Mar. 31, 2001, we conducted time-series analyses to measure any association with the release of the HOPE results.

Results — The monthly number of new prescriptions for ramipril from the time it was introduced in 1995 until HOPE's early termination, in April 1999, peaked at 58 per 100 000 elderly Ontario residents. The rate increased to 92/100 000 in May, coincident with newspaper coverage of the trial's early termination, then fell back to 63/100 000 in August. After HOPE's results were formally released, starting Aug. 31, the rate increased significantly; it peaked at 304/100 000 in May 2000 (p < 0.01). The market share of ramipril among ACE inhibitors also increased significantly (p < 0.01), both overall and among patients with diabetes or congestive heart failure.

Interpretation — HOPE led to a striking and unprecedented increase, over 400%, in ramipril prescribing to elderly Ontario residents, including those not eligible for the trial. Many physicians are now prescribing ramipril for patients with diabetes or congestive heart failure.