Antihypertensive Drug Therapies and the Risk of Ischemic Stroke

Background: The relative effectiveness of various antihypertensive drugs with regard to the reduction of stroke incidence remains uncertain. Objective: To assess the association between first ischemic stroke and use of antihypertensive drugs. Methods: A population-based case-control study was performed among enrollees of the Group Health Cooperative of Puget Sound. Case patients included pharmacologically treated hypertensive patients who sustained a first ischemic stroke (fatal or nonfatal; n = 380) between July 1, 1989, and December 31, 1996. Control subjects were a random sample of treated hypertensive enrollees without a history of a stroke (n = 2790). Medical record review and a telephone interview of consenting survivors were used to collect information on risk factors for stroke. Computerized pharmacy records were used to assess antihypertensive drug use. Results: Among 1237 single-drug users with no history of cardiovascular disease, the adjusted risk of ischemic stroke was higher among users of a [Beta]-blocker (risk ratio [RR], 2.03; 95% confidence interval [CI], 1.0-53.94), calcium channel blocker (RR, 2.30; 95% CI, 1.16-4.56), or angiotensin-converting enzyme inhibitor (RR, 2.79; 95% CI, 1.47-5.27) than among users of a thiazide diuretic alone. Among 673 single-drug users with a history of cardiovascular disease, the RRs were 1.22 (95% CI, 0.63-2.35), 1.18 (95% CI, 0.59-2.33), and 1.45 (95% CI, 0.70-3.02) among users of a [Beta]-blocker, calcium channel blocker, and angiotensin-converting enzyme inhibitor, respectively, compared with users of a thiazide diuretic alone. Conclusions: In this study of pharmacologically treated hypertensive patients, antihypertensive drug regimens that did not include a thiazide diuretic were associated with an increased risk of ischemic stroke compared with regimens that did include a thiazide. These results support the use of thiazide diuretics as first-line antihypertensive agents.