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Diuretics Still the Best First-Line Antihypertensive Choice


Am Fam Physician. 2003 Mar 15;67(6):1366.

The cost of antihypertensive drugs accounts for nearly one half of the expense of caring for patients with hypertension and its complications. To determine the relative efficacy of newer antihypertensive agents compared with older, less costly drugs, the research group of the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALL-HAT) compared a calcium channel blocker (amlodipine) or an angiotensin-converting enzyme inhibitor (lisinopril) with a diuretic (chlorthalidone). Primary outcomes were fatal and nonfatal coronary heart disease (CHD), and secondary outcomes were all-cause mortality and other CHD events.

ALLHAT was a double-blind, multicenter clinical trial with 33,357 participants randomized to one of three intervention arms.All participants were 55 years or older and had stage 1 or stage 2 hypertension with at least one other risk factor for CHD events. Follow-up blood pressure measurements took place at one, three, six, nine, and 12 months, and every four months thereafter. The target blood pressure was less than 140/90 mm Hg. Open-label atenolol, clonidine, or reserpine was added if additional medication was needed to reach target measurements.

Mean follow-up was 4.9 years. No significant difference was observed between amlodipine and chlorthalidone for the primary outcomes or for most secondary outcomes. Patients in the amlodipine group had a 38 percent higher risk of heart failure, with a six-year absolute risk difference of 2.5 percent and a 35 percent higher risk of hospitalized/fatal heart failure.

No significant differences in primary outcomes and most secondary outcomes were observed in the lisinopril versus chlorthali-done group. Patients in the lisinopril group had a 15 percent higher risk of stroke and a 10 percent increased risk of combined cardiovascular disease (CVD) events, with a six-year absolute risk difference of 2.4 percent. The following risks also were increased: heart failure (19 percent), hospitalized/fatal heart failure (10 percent), hospital-treated angina (11 percent), and revascularization (10 percent). The mean systolic blood pressure for all participants was 2 mm Hg higher in patients receiving lisinopril, 4 mm Hg higher in blacks, and 3 mm Hg in persons 65 years or older.

Lisinopril, amlodipine, and chlorthalidone were equivalent in preventing major coronary events and increasing survival rates. Chlorthalidone performed better than amlodipine in preventing heart failure as well as hospitalizations and fatalities, although it did not differ from amlodipine in overall prevention of CVD. Chlorthalidone also was superior to lisinopril in lowering blood pressure and preventing aggregate cardiovascular events, and in several CVD outcomes. The results of ALL-HAT suggest that thiazide type diuretics should remain first-line therapy for hypertension because of unsurpassed efficacy, safety, and tolerability, as well as lower cost.

The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) officers and coordinators for the ALL-HAT Collaborative Research Group. Major outcomes in high-risk hypertensive patients randomized to angiotensin-converting enzyme inhibitor or calcium channel blocker vs diuretic. JAMA. December 18, 2002;288:2981–97.



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