Use of ramipril in preventing stroke: double blind randomised trial

Abstract

Objective: To determine the effect of the angiotensin converting enzyme inhibitor ramipril on the secondary prevention of stroke.

Design: Randomised controlled trial with 2x2 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.

Figure 1

Kaplan-Meier estimates of the development of stroke by treatment group. The relative risk of developing stroke in the ramipril group compared with the placebo group was 0.68 (95% confidence interval 0.56 to 0.84; P=0.0002).

Figure 2

Impact of ramipril on stroke based on baseline blood pressure

Figure 3

Impact of ramipril on stroke rates among subgroups of patients with different baseline conditions. (‘−’ indicates absence of condition; ‘+’ indicates presence of condition; STK/TIA=stroke or transient ischaemic attack; CVD=cardiovascular disease; CAD=coronary artery disease; PAD=peripheral arterial disease; HTN=hypertension; DM=diabetes mellitus)

Figure 4

Impact of ramipril on stroke in subgroups of patients based on baseline drug use. *Interaction statistic derived from χ² test. (‘−’ indicates absence of condition; ‘+’ indicates presence of condition; CHOL LOWER=cholesterol lowering agent; BB=β blocker; DIUR=diuretic; CCB=calcium channel blocker)