Antihypertensive drug therapies and the risk of ischemic stroke

The relative effectiveness of various antihypertensive drugs with regard to the reduction of stroke incidence remains uncertain.

To assess the association between first ischemic stroke and use of antihypertensive drugs.

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.

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], 1.05-3.94), 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.

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.