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], 1.05-3.94), 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.


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.
Klungel
O H
OH
Department of Pharmacoepidemiology and Pharmacotherapy, Utrecht Institute of Pharmaceutical Sciences, Sorbonnelann 16, 3584 CA Utrecht, The Netherlands. o.h.klungel@pharm.uu.nl
Heckbert
S R
SR
Longstreth
W T
WT
Furberg
C D
CD
Kaplan
R C
RC
Smith
N L
NL
Lemaitre
R N
RN
Leufkens
H G
HG
de Boer
A
A
Psaty
B M
BM
D000319:Adrenergic beta-Antagonists / Q000627:therapeutic use; D000328:Adult; D000368:Aged; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use; D000959:Antihypertensive Agents / Q000627:therapeutic use*; D001581:Benzothiadiazines; D002545:Brain Ischemia / Q000453:epidemiology / Q000209:etiology* / Q000517:prevention & control*; D002121:Calcium Channel Blockers / Q000627:therapeutic use; D016022:Case-Control Studies; D004232:Diuretics; D005260:Female; D006801:Humans; D006973:Hypertension / Q000150:complications* / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D012307:Risk Factors; D049993:Sodium Chloride Symporter Inhibitors / Q000627:therapeutic use
D000319:Adrenergic beta-Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D001581:Benzothiadiazines; D002121:Calcium Channel Blockers; D004232:Diuretics; D049993:Sodium Chloride Symporter Inhibitors