Major outcomes in high-risk hypertensive patients randomized to angiotensin-converting enzyme inhibitor or calcium channel blocker vs diuretic: The antihypertensive and lipid-lowering treatment to prevent heart attack trial (ALLHAT)

Curt D. Furberg, Jackson T. Wright, Barry R. Davis, Jeffrey A. Cutler, Michael Alderman, Henry Black, William Cushman, Richard Grimm, L. Julian Haywood, Frans Leenen, Suzanne Oparil, Jeffrey Probstfield, Paul Whelton, Chuke Nwachuku, David Gordon, Michael Proschan, Paula Einhom, Charles E. Ford, Linda B. Piller, I. Kay DunnDavid Goff, Sara Pressel, Judy Bettencourt, Barbara DeLeon, Lara M. Simpson, Joe Blanton, Therese Geraci, Sandra M. Walsh, Christine Nelson, Mahboob Rahman, Anne Juratovac, Robert Pospisil, Lillian Carroll, Sheila Sullivan, Jeanne Russo, Gail Barone, Rudy Christian, Sharon Feldman, Tracy Lucente, David Calhoun, Kim Jenkins, Peggy McDowell, Janice Johnson, Connie Kingry, Juan Alzate, Karen L. Margolis, Leslie Ann Holland-Klemme, Brenda Jaeger, Jeffrey Williamson, Gail Louis, Pamela Ragusa, Angela Williard, R. L Sue Ferguson, Joanna Tanner, John Eckfeldt, Richard Crow, John Pelosi

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4593 Scopus citations

Abstract

Context: Antihypertensive therapy is well established to reduce hypertension-related morbidity and mortality, but the optimal first-step therapy is unknown. Objective: To determine whether treatment with a calcium channel blocker or an angiotensin-converting enzyme inhibitor lowers the incidence of coronary heart disease (CHD) or other cardiovascular disease (CVD) events vs treatment with a diuretic. Design: The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT), a randomized, double-blind, active-controlled clinical trial conducted from February 1994 through March 2002. Setting and Participants: A total of 33 357 participants aged 55 years or older with hypertension and at least 1 other CHD risk factor from 623 North American centers. Interventions: Participants were randomly assigned to receive chlorthalidone, 12.5 to 25 mg/d (n = 15255); amlodipine, 2.5 to 10 mg/d (n =9048); or lisinopril, 10 to 40 mg/d (n=9054) for planned follow-up of approximately 4 to 8 years. Main Outcome Measures: The primary outcome was combined fatal CHD or nonfatal myocardial infarction, analyzed by intent-to-treat. Secondary outcomes were all-cause mortality, stroke, combined CHD (primary outcome, coronary revascularization, or angina with hospitalization), and combined CVD (combined CHD, stroke, treated angina without hospitalization, heart failure [HF], and peripheral arterial disease). Results: Mean follow-up was 4.9 years. The primary outcome occurred in 2956 participants, with no difference between treatments. Compared with chlorthalidone (6-year rate, 11.5%), the relative risks (RRs) were 0.98 (95% Cl, 0.90-1.07) for amlodipine (6-year rate, 11.3%) and 0.99 (95% Cl, 0.91-1.08) for lisinopril (6-year rate, 11.4%). Likewise, all-cause mortality did not differ between groups. Five-year systolic blood pressures were significantly higher in the amiodipine (0.8 mm Hg, P=.03) and lisinopril (2 mm Hg, P<.001) groups compared with chlorthalidone, and 5-year diastolic blood pressure was significantly lower with amlodipine (0.8 mm Hg, P<.001). For amlodipine vs chiorthalidone, secondary outcomes were similar except for a higher 6-year rate of HF with amlodipine (10.2% vs 7.7%; RR, 1.38; 95% Cl, 1.25-1.52). For lisinopril vs chlorthalidone, lisinopril had higher 6-year rates of combined CVD (33.3% vs 30.9%; RR, 1.10; 95% Cl, 1.05-1.16); stroke (6.3% vs 5.6%; RR, 1.15; 95% Cl, 1.02-1.30); and HF (8.7% vs 7.7%; RR, 1.19; 95% Cl, 1.07-1.31). Conclusion: Thiazide-type diuretics are superior in preventing 1 or more major forms of CVD and are less expensive. They should be preferred for first-step antihypertensive therapy.

Original languageEnglish (US)
Pages (from-to)2981-2997
Number of pages17
JournalJournal of the American Medical Association
Volume288
Issue number23
DOIs
StatePublished - Dec 18 2002

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