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Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT)

Jackson T. Wright Jr, MD, PhD; Sonja Harris-Haywood, MD; Sara Pressel, MS; Joshua Barzilay, MD; Charles Baimbridge, MS; Charles J. Bareis, MD; Jan N. Basile, MD; Henry R. Black, MD; Richard Dart, MD; Alok K. Gupta, MD; Bruce P. Hamilton, MD; Paula T. Einhorn, MD, MS; L. Julian Haywood, MD; Syed Z. A. Jafri, MD; Gail T. Louis, RN, BA; Paul K. Whelton, MD, MSc; Cranford L. Scott, MD; Debra L. Simmons, MD; Carol Stanford, MD; Barry R. Davis, MD, PhD

Arch Intern Med. 2008;168(2):207-217.

Background  Antihypertensive drugs with favorable metabolic effects are advocated for first-line therapy in hypertensive patients with metabolic/cardiometabolic syndrome (MetS). We compared outcomes by race in hypertensive individuals with and without MetS treated with a thiazide-type diuretic (chlorthalidone), a calcium channel blocker (amlodipine besylate), an -blocker (doxazosin mesylate), or an angiotensin-converting enzyme inhibitor (lisinopril).

Methods  A subgroup analysis of the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT), a randomized, double-blind hypertension treatment trial of 42 418 participants. We defined MetS as hypertension plus at least 2 of the following: fasting serum glucose level of at least 100 mg/dL, body mass index (calculated as weight in kilograms divided by height in meters squared) of at least 30, fasting triglyceride levels of at least 150 mg/dL, and high-density lipoprotein cholesterol levels of less than 40 mg/dL in men or less than 50 mg/dL in women.

Results  Significantly higher rates of heart failure were consistent across all treatment comparisons in those with MetS. Relative risks (RRs) were 1.50 (95% confidence interval, 1.18-1.90), 1.49 (1.17-1.90), and 1.88 (1.42-2.47) in black participants and 1.25 (1.06-1.47), 1.20 (1.01-1.41), and 1.82 (1.51-2.19) in nonblack participants for amlodipine, lisinopril, and doxazosin comparisons with chlorthalidone, respectively. Higher rates for combined cardiovascular disease were observed with lisinopril-chlorthalidone (RRs, 1.24 [1.09-1.40] and 1.10 [1.02-1.19], respectively) and doxazosin-chlorthalidone comparisons (RRs, 1.37 [1.19-1.58] and 1.18 [1.08-1.30], respectively) in black and nonblack participants with MetS. Higher rates of stroke were seen in black participants only (RR, 1.37 [1.07-1.76] for the lisinopril-chlorthalidone comparison, and RR, 1.49 [1.09-2.03] for the doxazosin-chlorthalidone comparison). Black patients with MetS also had higher rates of end-stage renal disease (RR, 1.70 [1.13-2.55]) with lisinopril compared with chlorthalidone.

Conclusions  The ALLHAT findings fail to support the preference for calcium channel blockers, -blockers, or angiotensin-converting enzyme inhibitors compared with thiazide-type diuretics in patients with the MetS, despite their more favorable metabolic profiles. This was particularly true for black participants.

Trial Registration  clinicaltrials.gov Identifier: NCT00000542

Author Affiliations: Department of Medicine, General Clinical Research Center (Dr Wright), and Department of Family Medicine, Case Western Reserve University (Dr Harris-Haywood), Cleveland, Ohio; Coordinating Center for Clinical Trials, School of Public Health, The University of Texas Health Science Center at Houston (Ms Pressel, Mr Baimbridge, and Dr Davis); Kaiser Permanente of Georgia, Tucker (Dr Barzilay); Department of Medicine, MacNeal Center for Clinical Research, Berwyn, Illinois (Dr Bareis); Ralph H. Johnson Veterans Affairs Medical Center and Medical University of South Carolina, Charleston (Dr Basile); Section of Cardiology, Department of Internal Medicine, New York University School of Medicine, New York (Dr Black); Department of Nephrology, Marshfield Clinic, Marshfield, Wisconsin (Dr Dart); Pennington Biomedical Research Center, Baton Rouge, Louisiana (Dr Gupta); Hypertension-Endocrine Unit, Veterans Affairs Medical Center, Baltimore, Maryland (Dr Hamilton); Division of Prevention and Population Sciences, National Heart, Lung, and Blood Institute, Bethesda, Maryland (Dr Einhorn); Division of Cardiovascular Medicine, University of Southern California Medical Center, Los Angeles (Dr Haywood); Department of Cardiology, Veterans Affairs Medical Center, Fargo, North Dakota (Dr Jafri); Tulane University Health Sciences Center, New Orleans, Louisiana (Ms Louis); Loyola University Medical Center, Maywood, Illinois (Dr Whelton); Cranford L. Scott, MD, Inc, Inglewood, California (Dr Scott); Department of Endocrinology, University of Arkansas for Medical Sciences, Little Rock (Dr Simmons); and University of Missouri Kansas City School of Medicine (Dr Stanford).