Context: Diuretic-based therapy is at least as effective as newer classes of agents for hypertension. However, many patients with hypertension require treatment with more than 1 drug class to achieve blood pressure control. The relative benefits or risks of 2-drug-class combinations are not well known. Objective: To prospectively evaluate if there are differences in cardiovascular mortality among postmenopausal women with hypertension but no history of cardiovascular disease (CVD) treated with different classes of antihypertensive agents, singly or in combination. Design, Setting, and Participants: Women with hypertension enrolled in the Women's Health Initiative Observational Study, a longitudinal multicenter cohort study of 93 676 women aged 50 to 79 years at baseline (1994-1998), assessed for a mean of 5.9 years. Main Outcome Measures: Relationship between baseline use of ACE inhibitors, β-blockers, calcium channel blockers, or diuretics, or a combination of these, and incidence of coronary heart disease, stroke, and CVD mortality. Results: Among 30219 women with hypertension but no history of CVD, 11 294 (57%) were receiving monotherapy with an ACE inhibitor, β-blocker, calcium channel blocker, or diuretic, and 4493 (23%) were treated at baseline with a combination of diuretic plus either ACE inhibitor, β-blocker, or calcium channel blocker or ACE inhibitor plus calcium channel blocker. Monotherapy with calcium channel blockers vs diuretics was associated with greater risk of CVD death (hazard ratio, 1.55; 95% confidence interval, 1.02-2.35), controlling for multiple covariates. Women treated with a diuretic plus a calcium channel blocker had an 85% greater risk of CVD death vs those treated with a diuretic plus a β-blocker, after adjustment for age, race, smoking, high cholesterol levels requiring medication, body mass index, physical activity, use of hormone therapy, and diabetes. After exclusion of women with diabetes the hazard ratio was 2.16 (95% confidence interval, 1.16-4.03). Analyses adjusting for propensity to be receiving a particular treatment did not change the results. For morbid events of coronary heart disease or stroke, diuretics plus ACE inhibitors or calcium channel blockers did not differ from diuretics plus β-blockers. Conclusions: Among women with hypertension but no history of CVD, a 2-drug-class regimen of calcium channel blockers plus diuretics was associated with a higher risk of CVD mortality vs β-blockers plus diuretics. Risks were similar for ACE inhibitors plus diuretics and β-blockers plus diuretics. Monotherapy with diuretics was equal or superior to other monotherapy in preventing CVD complications of high blood pressure.
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