ALLHAT findings revisited in the context of subsequent analyses, other trials, and meta-analyses.
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 alpha-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.
ALLHAT Clinical Trials Center, University of Texas at Houston Health Science Center School of Public Health, 1200 Herman Pressler Street, Houston, TX 77030, USA.
Jackson T
JT
Wright
Jeffrey L
JL
Probstfield
William C
WC
Cushman
Sara L
SL
Pressel
Jeffrey A
JA
Cutler
Barry R
BR
Davis
Paula T
PT
Einhorn
Mahboob
M
Rahman
Paul K
PK
Whelton
Charles E
CE
Ford
L Julian
LJ
Haywood
Karen L
KL
Margolis
Suzanne
S
Oparil
Henry R
HR
Black
Michael H
MH
Alderman
D000368:Aged; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D000959:Antihypertensive Agents / Q000627:therapeutic use*; D002121:Calcium Channel Blockers / Q000627:therapeutic use*; D002752:Chlorthalidone / Q000627:therapeutic use; D003920:Diabetes Mellitus / Q000139:chemically induced / Q000517:prevention & control*; D004232:Diuretics / Q000009:adverse effects / Q000627:therapeutic use*; D004311:Double-Blind Method; D005260:Female; D006333:Heart Failure / Q000517:prevention & control*; D006801:Humans; D000960:Hypolipidemic Agents / Q000627:therapeutic use*; D007676:Kidney Failure, Chronic / Q000517:prevention & control; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000517:prevention & control*; D012189:Retrospective Studies
D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D002121:Calcium Channel Blockers; D004232:Diuretics; D000960:Hypolipidemic Agents; D002752:Chlorthalidone