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Original Contribution
April 6, 2005

Outcomes in Hypertensive Black and Nonblack Patients Treated With Chlorthalidone, Amlodipine, and Lisinopril

Author Affiliations

Author Affiliations: General Clinical Research Center, Case Western Reserve University, Cleveland, Ohio (Dr Wright); School of Public Health, University of Texas Health Science Center at Houston (Drs Dunn, Davis, and Ford); Division of Epidemiology and Clinical Applications, National Heart, Lung, and Blood Institute, Bethesda, Md (Dr Cutler); Memphis Veterans Affairs Medical Center, Memphis, Tenn (Dr Cushman); Los Angeles County/University of Southern California Medical Center, Los Angeles (Dr Haywood); University of Ottawa Heart Institute, Ottawa, Ontario (Dr Leenen); Berman Center for Outcomes and Clinical Research and Hennepen County Medical Center, Minneapolis, Minn (Dr Margolis); Veterans Affairs Medical Center, Washington, DC (Dr Papademetriou); University of Washington, Seattle (Dr Probstfield); Tulane University Health Sciences Center, New Orleans, La (Dr Whelton); and Houston Veterans Affairs Medical Center, Houston, Tex (Dr Habib).

JAMA. 2005;293(13):1595-1608. doi:10.1001/jama.293.13.1595

Context Few cardiovascular outcome data are available for blacks with hypertension treated with angiotensin-converting enzyme (ACE) inhibitors or calcium channel blockers (CCBs).

Objective To determine whether an ACE inhibitor or CCB is superior to a thiazide-type diuretic in reducing cardiovascular disease (CVD) incidence in racial subgroups.

Design, Setting, and Participants Prespecified subgroup analysis of ALLHAT, a randomized, double-blind, active-controlled, clinical outcome trial conducted between February 1994 and March 2002 in 33 357 hypertensive US and Canadian patients aged 55 years or older (35% black) with at least 1 other cardiovascular risk factor.

Interventions Antihypertensive regimens initiated with a CCB (amlodipine) or an ACE inhibitor (lisinopril) vs a thiazide-type diuretic (chlorthalidone). Other medications were added to achieve goal blood pressures (BPs) less than 140/90 mm Hg.

Main Outcome Measures The primary outcome was combined fatal coronary heart disease (CHD) or nonfatal myocardial infarction (MI), analyzed by intention-to-treat. Secondary outcomes included all-cause mortality, stroke, combined CVD (CHD death, nonfatal MI, stroke, angina, coronary revascularization, heart failure [HF], or peripheral vascular disease), and end-stage renal disease.

Results No significant difference was found between treatment groups for the primary CHD outcome in either racial subgroup. For amlodipine vs chlorthalidone only, HF was the only prespecified clinical outcome that differed significantly (overall: relative risk [RR], 1.37; 95% confidence interval [CI], 1.24-1.51; blacks: RR, 1.46; 95% CI, 1.24-1.73; nonblacks: RR, 1.32; 95% CI, 1.17-1.49; P<.001 for each comparison) with no difference in treatment effects by race (P = .38 for interaction). For lisinopril vs chlorthalidone, results differed by race for systolic BP (greater decrease in blacks with chlorthalidone), stroke, and combined CVD outcomes (P<.001, P = .01, and P = .04, respectively, for interactions). In blacks and nonblacks, respectively, the RRs for stroke were 1.40 (95% CI, 1.17-1.68) and 1.00 (95% CI, 0.85-1.17) and for combined CVD were 1.19 (95% CI, 1.09-1.30) and 1.06 (95% CI, 1.00-1.13). For HF, the RRs were 1.30 (95% CI, 1.10-1.54) and 1.13 (95% CI, 1.00-1.28), with no significant interaction by race. Time-dependent BP adjustment did not significantly alter differences in outcome for lisinopril vs chlorthalidone in blacks.

Conclusions In blacks and nonblack subgroups, rates were not lower in the amlodipine or lisinopril groups than in the chlorthalidone group for either the primary CHD or any other prespecified clinical outcome, and diuretic-based treatment resulted in the lowest risk of heart failure. While the improved outcomes with chlorthalidone were more pronounced for some outcomes in blacks than in nonblacks, thiazide-type diuretics remain the drugs of choice for initial therapy of hypertension in both black and nonblack hypertensive patients.