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Antihypertensive Drug Therapies and the Risk of Ischemic Stroke
Olaf H. Klungel, PharmD, PhD;
Susan R. Heckbert, MD, PhD;
W. T. Longstreth, Jr, MD, MPH;
Curt D. Furberg, MD, PhD;
Robert C. Kaplan, MS, PhD;
Nicholas L. Smith, MPH, PhD;
Rozenn N. Lemaitre, MPH, PhD;
Hubert G. M. Leufkens, PharmD, PhD;
Anthonius de Boer, MD, PhD;
Bruce M. Psaty, MD, PhD
Arch Intern Med. 2001;161:37-43.
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 ß-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 ß-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.
From the Cardiovascular Health Research Unit, Departments of Epidemiology
(Drs Klungel, Heckbert, Longstreth, Kaplan, Smith, and Psaty), Medicine (Drs
Longstreth, Lemaitre, and Psaty), Neurology (Dr Longstreth), and Health Services
(Dr Psaty), University of Washington, Seattle; the Department of Pharmacoepidemiology
and Pharmacotherapy, Utrecht Institute of Pharmaceutical Sciences, Utrecht,
the Netherlands (Drs Klungel, Leufkens, and de Boer); and the Department of
Public Health Sciences, Wake Forest University School of Medicine, Winston-Salem,
NC (Dr Furberg).
Corresponding author and reprints: Olaf H. Klungel, PharmD, PhD,
Department of Pharmacoepidemiology and Pharmacotherapy, Utrecht Institute
of Pharmaceutical Sciences, Sorbonnelann 16, 3584 CA Utrecht, the Netherlands
(e-mail: o.h.klungel{at}pharm.uu.nl).
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