ACE inhibitors prevent stroke in high-risk patients, independent of blood pressure-lowering effect

ABSTRACT

BACKGROUND: Studies have shown that strokes can be prevented by lowering blood pressure in hypertensive patients. Recent experimental and human data suggest that angiotensin-converting enzyme (ACE) inhibitors may lower ischemic vascular events independent of lowering blood pressure. This report evaluated the effect of ramipril on the incidence and severity of strokes in a population at high risk for cardiovascular events with a wide range of blood pressures.

POPULATION STUDIED: This report is a secondary analysis of data from the HOPE study, a double-blind randomized trial of ramipril, vitamin E, or the combination in patients at high risk for cardiovascular events. The 9297 patients in this study were all 55 years of age or older and had a history of vascular disease (coronary artery, peripheral, or cerebrovascular) or diabetes plus at least 1 other cardiovascular risk factor. Patients were excluded if they were taking either an ACE inhibitor or vitamin E; had heart failure or a known left ventricular ejection fraction of less than 40%; known proteinuria; uncontrolled hypertension; or a previous stroke or myocardial infarction less than 1 month before enrollment. The patients had an average blood pressure of 139/79 mm Hg, although 46% had mild, previously undiagnosed hypertension.

STUDY DESIGN AND VALIDITY: In the HOPE study, patients were randomized to receive up to 10 mg ramipril daily, 400 IU vitamin E, both, or matching placebos and were then followed for an average of 4.5 years. Vitamin E was shown to be ineffective.

OUTCOMES MEASURED: The primary outcome was the occurrence of stroke or transient ischemic attacks (TIAs). Symptoms and functional impairment were recorded for every stroke. Blood pressure was also measured at enrollment, after 2 years, and at the end of the study.

RESULTS: The relative risk (RR) of any stroke was reduced by 32% (3.4% vs 4.9%) in the ramipril group compared with the placebo group (RR = 0.68; 95% confidence interval [CI], 0.56–0.84). This reduction translates into a number needed to treat (NNT) of 67; ie, 1 stroke would be prevented over 4.5 years for every 67 patients treated with ramipril instead of placebo. Fatal stroke was reduced 61% (0.4% vs1.0%) with ramipril treatment (RR = 0.39; 95% CI, 0.22–0.67), with an NNT of 166 for 4.5 years. Nonfatal stroke was reduced 24% (3.0% vs 3.9%) with ramipril treatment (RR = 0.76; 95% CI, 0.61–0.94), with an NNT of 111. The relative risk of a TIA was reduced 17% (4.1% vs 4.9%) with ramipril treatment (0.83; 95% CI, 0.68–0.1.00; P = .052), with an NNT of 125. Overall, patients taking ramipril had a significantly reduced combined risk of stroke and TIA of 23% (6.8% vs 8.7%) compared with placebo (RR = 0.77; 95% CI, 0.66–0.89; P = .0004). The NNT for the combined end point was 53. Additionally, patients who experienced a stroke despite treatment were less likely to have residual cognitive or functional impairment. These benefits were consistent across baseline blood pressures and subgroups of cardiovascular risk factors. ACE inhibitor treatment reduced systolic blood pressure by an average of 3.8 mm Hg and diastolic blood pressure by an average of 2.8 mm Hg.