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Special Article
May 11, 2009

ALLHAT Findings Revisited in the Context of Subsequent Analyses, Other Trials, and Meta-analyses

Author Affiliations

Author Affiliations: Case Western Reserve University, Cleveland, Ohio (Drs Wright and Rahman); University of Washington Clinical Trials Service Unit, Seattle (Dr Probstfield); Veterans Affairs Medical Center, Memphis, Tennessee (Dr Cushman); University of Texas Health Science Center at Houston School of Public Health, Houston (Ms Pressel and Drs Davis and Ford); National Heart, Lung, and Blood Institute, Bethesda, Maryland (Drs Cutler and Einhorn); Loyola University Medical Center and Health System, Maywood, Illinois (Dr Whelton); University of Southern California Medical Center, Los Angeles (Dr Haywood); Health Partners Research Foundation, Minneapolis, Minnesota (Dr Margolis); University of Alabama at Birmingham (Dr Oparil); New York University School of Medicine, New York (Dr Black); and Albert Einstein College of Medicine, Department of Epidemiology and Social Medicine, Bronx, New York (Dr Alderman).Group Information: A complete list of the participants in the ALLHAT Collaborative Research Group is available in JAMA (2002;288[23]:2981-2997).

Arch Intern Med. 2009;169(9):832-842. doi:10.1001/archinternmed.2009.60

The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) is reevaluated considering information from new clinical trials, meta-analyses, and recent subgroup and explanatory analyses from ALLHAT, especially those regarding heart failure (HF) and the association of drug treatment with new-onset diabetes mellitus (DM) and its cardiovascular disease (CVD) consequences. Chlorthalidone was superior to (1) doxazosin mesylate in preventing combined CVD (CCVD) (risk ratio [RR], 1.20; 95% confidence interval [CI], 1.13-1.27), especially HF (RR, 1.80; 95% CI, 1.40-2.22) and stroke (RR, 1.26; 95% CI, 1.10-1.46); (2) lisinopril in preventing CCVD (RR, 1.10; 95% CI, 1.05-1.16), including stroke (in black persons only) and HF (RR, 1.20; 95% CI, 1.09-1.34); and (3) amlodipine besylate in preventing HF, overall (by 28%) and in hospitalized or fatal cases (by 26%). Central independent blinded reassessment of HF hospitalizations confirmed each comparison. Results were consistent by age, sex, race (except for stroke and CCVD), DM status, metabolic syndrome status, and renal function level. Neither amlodipine nor lisinopril was superior to chlorthalidone in preventing end-stage renal disease overall, by DM status, or by renal function level. In the chlorthalidone arm, new-onset DM was not significantly associated with CCVD (RR, 0.96; 95% CI, 0.88-2.42). Evidence from subsequent analyses of ALLHAT and other clinical outcome trials confirm that neither α-blockers, angiotensin-converting enzyme inhibitors, nor calcium channel blockers surpass thiazide-type diuretics (at appropriate dosage) as initial therapy for reduction of cardiovascular or renal risk. Thiazides are superior in preventing HF, and new-onset DM associated with thiazides does not increase CVD outcomes.