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Special Article |

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

Jackson T. Wright Jr, MD, PhD; Jeffrey L. Probstfield, MD; William C. Cushman, MD; Sara L. Pressel, MS; Jeffrey A. Cutler, MD, MPH; Barry R. Davis, MD, PhD; Paula T. Einhorn, MD, MS; Mahboob Rahman, MD, MS; Paul K. Whelton, MD, MSc; Charles E. Ford, PhD; L. Julian Haywood, MD; Karen L. Margolis, MD, MPH; Suzanne Oparil, MD; Henry R. Black, MD; Michael H. Alderman, MD ; ALLHAT Collaborative Research Group
Arch Intern Med. 2009;169(9):832-842. doi:10.1001/archinternmed.2009.60.
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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.

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Figure 1.

Four-year systolic/diastolic blood pressure difference and RRs (95% CIs) for clinical outcomes for newer agents compared with chlorthalidone, 12.5 to 25 mg/d, in prespecified subgroups. Data are given for coronary heart disease (CHD), combined cardiovascular disease (CCVD), heart failure (HF), stroke, and end-stage renal disease (ESRD). CI indicates confidence interval; DM, diabetes mellitus; and RR, relative risk. The figure is adapted from articles by the ALLHAT Officers and Coordinators for the ALLHAT Collaborative Research Group1 and Whelton et al.9 Amlodipine besylate and chlorthalidone are compared.

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Figure 2.

Four-year systolic/diastolic blood pressure difference and RRs (95% CIs) for clinical outcomes for newer agents compared with chlorthalidone, 12.5 to 25 mg/d, in prespecified subgroups. Data are given for coronary heart disease (CHD), combined cardiovascular disease (CCVD), heart failure (HF), stroke, and end-stage renal disease (ESRD). CI indicates confidence interval; DM, diabetes mellitus; and RR, relative risk. The figure is adapted from articles by the ALLHAT Officers and Coordinators for the ALLHAT Collaborative Research Group1 and Whelton et al.9 Lisinopril and chlorthalidone are compared.

Graphic Jump Location
Place holder to copy figure label and caption
Figure 3.

Four-year systolic/diastolic blood pressure difference and RRs (95% CIs) for clinical outcomes for newer agents compared with chlorthalidone, 12.5 to 25 mg/d, in prespecified subgroups. Data are given for coronary heart disease (CHD), combined cardiovascular disease (CCVD), heart failure (HF), stroke, and end-stage renal disease (ESRD). CI indicates confidence interval; DM, diabetes mellitus; and RR, relative risk. The figure is adapted from articles by the ALLHAT Officers and Coordinators for the ALLHAT Collaborative Research Group1 and Whelton et al.9 Doxazosin mesylate and chlorthalidone are compared.

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The American Medical Association is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians. The AMA designates this journal-based CME activity for a maximum of 1 AMA PRA Category 1 CreditTM per course. Physicians should claim only the credit commensurate with the extent of their participation in the activity. Physicians who complete the CME course and score at least 80% correct on the quiz are eligible for AMA PRA Category 1 CreditTM.
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