Use of ramipril in preventing stroke: double blind randomised trial

OBJECTIVE: To determine the effect of the angiotensin converting enzyme inhibitor ramipril on the secondary prevention of stroke. DESIGN: Randomised controlled trial with 2×2 factorial design. SETTING: 267 hospitals in 19 countries. PARTICIPANTS: 9297 patients with vascular disease or diabetes plus an additional risk factor, followed for 4.5 years as part of the HOPE study. OUTCOME MEASURES: Stroke (confirmed by computed tomography or magnetic resonance imaging when available), transient ischaemic attack, and cognitive function. Blood pressure was recorded at entry to the study, after 2 years, and at the end of the study. RESULTS: Reduction in blood pressure was modest (3.8 mm Hg systolic and 2.8 mm Hg diastolic). The relative risk of any stroke was reduced by 32% (156 v 226) in the ramipril group compared with the placebo group, and the relative risk of fatal stroke was reduced by 61% (17 v 44). Benefits were consistent across baseline blood pressures, drugs used, and subgroups defined by the presence or absence of previous stroke, coronary artery disease, peripheral arterial disease, diabetes, or hypertension. Significantly fewer patients on ramipril had cognitive or functional impairment. CONCLUSION: Ramipril reduces the incidence of stroke in patients at high risk, despite a modest reduction in blood pressure.