Outcomes in hypertensive black and nonblack patients treated with chlorthalidone, amlodipine, and lisinopril

Jackson T. Wright, J. Kay Dunn, Jeffrey A. Cutler, Barry R. Davis, William Cushman, Charles E. Ford, L. Julian Haywood, Frans H.H. Leenen, Karen L. Margolis, Vasilios Papademetriou, Jeffrey L. Probstfield, Paul K. Whelton, Gabriel B. Habib

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Abstract

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.

Original languageEnglish (US)
Pages (from-to)1595-1608
Number of pages14
JournalJournal of the American Medical Association
Volume293
Issue number13
DOIs
StatePublished - Apr 6 2005

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Chlorthalidone
Lisinopril
Amlodipine
Confidence Intervals
Sodium Chloride Symporter Inhibitors
Coronary Disease
Calcium Channel Blockers
Cardiovascular Diseases
Heart Failure
Stroke
Angiotensin-Converting Enzyme Inhibitors
Blood Pressure
Myocardial Infarction
Hypertension
Social Adjustment
Peripheral Vascular Diseases
Controlled Clinical Trials
Therapeutics
Diuretics
Antihypertensive Agents

All Science Journal Classification (ASJC) codes

  • Medicine(all)

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Outcomes in hypertensive black and nonblack patients treated with chlorthalidone, amlodipine, and lisinopril. / Wright, Jackson T.; Dunn, J. Kay; Cutler, Jeffrey A.; Davis, Barry R.; Cushman, William; Ford, Charles E.; Haywood, L. Julian; Leenen, Frans H.H.; Margolis, Karen L.; Papademetriou, Vasilios; Probstfield, Jeffrey L.; Whelton, Paul K.; Habib, Gabriel B.

In: Journal of the American Medical Association, Vol. 293, No. 13, 06.04.2005, p. 1595-1608.

Research output: Contribution to journalArticle

Wright, JT, Dunn, JK, Cutler, JA, Davis, BR, Cushman, W, Ford, CE, Haywood, LJ, Leenen, FHH, Margolis, KL, Papademetriou, V, Probstfield, JL, Whelton, PK & Habib, GB 2005, 'Outcomes in hypertensive black and nonblack patients treated with chlorthalidone, amlodipine, and lisinopril', Journal of the American Medical Association, vol. 293, no. 13, pp. 1595-1608. https://doi.org/10.1001/jama.293.13.1595
Wright, Jackson T. ; Dunn, J. Kay ; Cutler, Jeffrey A. ; Davis, Barry R. ; Cushman, William ; Ford, Charles E. ; Haywood, L. Julian ; Leenen, Frans H.H. ; Margolis, Karen L. ; Papademetriou, Vasilios ; Probstfield, Jeffrey L. ; Whelton, Paul K. ; Habib, Gabriel B. / Outcomes in hypertensive black and nonblack patients treated with chlorthalidone, amlodipine, and lisinopril. In: Journal of the American Medical Association. 2005 ; Vol. 293, No. 13. pp. 1595-1608.
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title = "Outcomes in hypertensive black and nonblack patients treated with chlorthalidone, amlodipine, and lisinopril",
abstract = "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.",
author = "Wright, {Jackson T.} and Dunn, {J. Kay} and Cutler, {Jeffrey A.} and Davis, {Barry R.} and William Cushman and Ford, {Charles E.} and Haywood, {L. Julian} and Leenen, {Frans H.H.} and Margolis, {Karen L.} and Vasilios Papademetriou and Probstfield, {Jeffrey L.} and Whelton, {Paul K.} and Habib, {Gabriel B.}",
year = "2005",
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doi = "10.1001/jama.293.13.1595",
language = "English (US)",
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TY - JOUR

T1 - Outcomes in hypertensive black and nonblack patients treated with chlorthalidone, amlodipine, and lisinopril

AU - Wright, Jackson T.

AU - Dunn, J. Kay

AU - Cutler, Jeffrey A.

AU - Davis, Barry R.

AU - Cushman, William

AU - Ford, Charles E.

AU - Haywood, L. Julian

AU - Leenen, Frans H.H.

AU - Margolis, Karen L.

AU - Papademetriou, Vasilios

AU - Probstfield, Jeffrey L.

AU - Whelton, Paul K.

AU - Habib, Gabriel B.

PY - 2005/4/6

Y1 - 2005/4/6

N2 - 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.

AB - 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.

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