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Does Ramipril Prevent Stroke and Stroke-Related Disability?

This subanalysis from the HOPE study suggests that the ACEI ramipril reduces stroke risk, perhaps independent of its effects on blood pressure.

Preclinical and clinical data suggest that angiotensin-converting-enzyme inhibitors (ACEIs) may reduce the risk for ischemic events independent of the drugs' blood pressure-lowering effects. This is an analysis of the impact of the ACEI ramipril on stroke, its subtypes, and related disability from the industry-sponsored Heart Outcomes Prevention Evaluation (HOPE) trial, a double-blind, randomized, 2x2-factorial-designed trial comparing up to 10 mg ramipril, 400 IU of vitamin E, both treatments, or matching placebos. Participants were 9541 people older than 55 who had either histories of cardiovascular or cerebrovascular disease or diabetes plus one additional risk factor. At study entry, 11% had had a previous stroke or TIA, and mean blood pressure (BP) was 139/79 mm Hg. Average follow-up was 4.5 years.

BP dropped modestly in the ramipril group (average decrease, 3.8/2.8 mm Hg). Absolute risk reduction (ARR) significantly favored ramipril over placebo for reductions in total stroke (by 1.5%), nonfatal stroke (by 0.9%), and fatal stroke (by 0.6%). The ramipril group also had a significantly larger proportion with no functional impairment (ARR, 0.6%) or only some impairment (ARR, 0.5%) and a smaller proportion with a change in cognition (ARR, 0.5%). The ARR for ischemic stroke with ramipril was 1.2%, but the trend for hemorrhagic-stroke reduction was nonsignificant (ARR, 0.08%). Benefits were observed regardless of baseline BP level, drugs used, and presence or absence of prior stroke, coronary disease, peripheral arterial disease, diabetes, or hypertension.

Comment: Ramipril appears to be a winner: These researchers found across-the-board benefits with ramipril for reductions of stroke and its major sequelae. One must interpret the data cautiously, however. The numbers needed to treat to prevent one stroke are relatively high. Furthermore, certain subgroups may experience less benefit (e.g., those with prior stroke or TIA; aspirin or calcium channel blocker users). As an accompanying editorial points out, this limitation for aspirin users raises the nagging question of whether ACEIs interact negatively with aspirin.

Finally, in an ambulatory BP-monitoring substudy of the HOPE trial (Hypertension 2001; 38:E28), there were more profound BP-lowering effects at night than those measured in the daytime ambulatory clinic (ramipril was given in the evening). Thus, there may be more to the story of "modest" BP lowering in the HOPE trial. If one considers both the HOPE study and PROGRESS (Perindopril Protection Against Recurrent Stroke Study), there is consistent and mounting evidence that ACEIs are important treatments in preventing first and recurrent stroke.

— Philip B. Gorelick, MD, MPH

Dr. Gorelick is Professor and Director, Section of Cerebrovascular Disease and Neurologic Critical Care, Rush Medical College, Chicago.

Published in Journal Watch Neurology May 23, 2002

Citation(s):

Bosch J et al. Use of ramipril in preventing stroke: double blind randomised trial. BMJ 2002 Mar 23; 324:699-702.

• Original article (Subscription may be required)
• Medline abstract (Free)

Schrader J and Lüders S. Preventing stroke. BMJ 2002 Mar 23; 324:687-8.

• Original article (Subscription may be required)
• Medline abstract (Free)