Certain high blood pressure combination therapies elevate risk for death from cardiovascular disease

December 14, 2004

Patients with high blood pressure who take calcium channel blockers and diuretics have an increased risk for cardiovascular disease (CVD) death compared to patients who take beta-blockers plus diuretics, according to a study in the December 15 issue of JAMA. Other findings indicate that diuretics may be the preferred single high blood pressure medication in preventing CVD complications.

According to background information in the article, several types of medications are used to treat high blood pressure, including diuretics, beta-blockers, angiotensin-converting enzyme (ACE) inhibitors and calcium channel blockers. While previous research has indicated that diuretics are equal or superior to other high blood pressure medications as the first step as monotherapy, most patients with hypertension require more than one drug class to control hypertension. It has been unresolved as to which of the other drug classes added to diuretics has better effects on cardiovascular complications.

Sylvia Wassertheil-Smoller, Ph.D., of the Albert Einstein College of Medicine, Bronx, N.Y., and colleagues examined the relation of different classes of antihypertensive drugs to the incidence of coronary heart disease, stroke, and CVD death. The researchers analyzed data for women with hypertension enrolled in the Women's Health Initiative Observational Study, a multicenter study of 93,676 women aged 50 to 79 years at baseline (1994-1998), assessed for an average of 5.9 years.

Among 30,219 women with hypertension but no history of CVD, 19,889 were on pharmacological antihypertensive treatment, of whom 11,294 (57 percent) were receiving monotherapy with an ACE inhibitor, beta-blocker, calcium channel blocker, or diuretic, and 4,493 (23 percent) were treated at baseline with a combination of diuretic plus either ACE inhibitor, beta-blocker, or calcium channel blocker or ACE inhibitor plus calcium channel blocker. The researchers found that among 2-drug-class combinations, diuretics plus calcium channel blockers were associated with approximately doubling of the risk of CVD death compared with diuretics plus beta-blockers. For events related to coronary heart disease or stroke, diuretics plus ACE inhibitors or calcium channel blockers did not differ from diuretics plus beta-blockers. Monotherapy with calcium channel blockers vs. diuretics was associated with a 55 percent increased risk of CVD death.

"The findings of this observational study concerning monotherapy are consistent with the comparative clinical trials published thus far and support the current guidelines set forth in the report of the JNC 7 [Joint National Committee on Prevention, Detection, Evaluation and Treatment of High Blood Pressure], which recommend low-dose diuretic therapy for most patients with hypertension," the authors write. (JAMA. 2004; 292:2849-2859. Available post-embargo at www.jama.com)
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Editor's Note: The Women's Health Initiative (WHI) program is funded by the National Heart, Lung and Blood Institute (NHLBI). Co-author Dr. Psaty has received honoraria from Celera Diagnostics. Co-author Dr. Black has served as a consultant for Astra-Zeneca, Biovail, Bristol-Myers Squibb, Merck Sharp & Dohme, Novartis, and Pfizer and has served on the speakers bureau for Astra-Zeneca, Merck Sharp & Dohme, Novartis, and Pfizer.

The JAMA Network Journals

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