Heart failure with preserved and reduced left ventricular ejection fraction in the antihypertensive and lipid-lowering treatment to prevent heart attack trial.
BACKGROUND
Heart failure (HF) developing in hypertensive patients may occur with preserved or reduced left ventricular ejection fraction (PEF [>or=50%] or REF [<50%]). In the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT), 42 418 high-risk hypertensive patients were randomized to chlorthalidone, amlodipine, lisinopril, or doxazosin, providing an opportunity to compare these treatments with regard to occurrence of hospitalized HFPEF or HFREF.


RESULTS
HF diagnostic criteria were prespecified in the ALLHAT protocol. EF estimated by contrast ventriculography, echocardiography, or radionuclide study was available in 910 of 1367 patients (66.6%) with hospitalized events meeting ALLHAT criteria. Cox regression models adjusted for baseline characteristics were used to examine treatment differences for HF (overall and by PEF and REF). HF case fatality rates were examined. Of those with EF data, 44.4% had HFPEF and 55.6% had HFREF. Chlorthalidone reduced the risk of HFPEF compared with amlodipine, lisinopril, or doxazosin; the hazard ratios were 0.69 (95% confidence interval [CI], 0.53 to 0.91; P=0.009), 0.74 (95% CI, 0.56 to 0.97; P=0.032), and 0.53 (95% CI, 0.38 to 0.73; P<0.001), respectively. Chlorthalidone reduced the risk of HFREF compared with amlodipine or doxazosin; the hazard ratios were 0.74 (95% CI, 0.59 to 0.94; P=0.013) and 0.61 (95% CI, 0.47 to 0.79; P<0.001), respectively. Chlorthalidone was similar to lisinopril with regard to incidence of HFREF (hazard ratio, 1.07; 95% CI, 0.82 to 1.40; P=0.596). After HF onset, death occurred in 29.2% of participants (chlorthalidone/amlodipine/lisinopril) with new-onset HFPEF versus 41.9% in those with HFREF (P<0.001; median follow-up, 1.74 years); and in the chlorthalidone/doxazosin comparison that was terminated early, 20.0% of HFPEF and 26.0% of HFREF patients died (P=0.185; median follow-up, 1.55 years).


CONCLUSIONS
In ALLHAT, with adjudicated outcomes, chlorthalidone significantly reduced the occurrence of new-onset hospitalized HFPEF and HFREF compared with amlodipine and doxazosin. Chlorthalidone also reduced the incidence of new-onset HFPEF compared with lisinopril. Among high-risk hypertensive men and women, HFPEF has a better prognosis than HFREF.
Davis
Barry R
BR
University of Texas Health Science Center School of Public Health, Houston, TX 77030, USA. barry.r.davis@uth.tmc.edu
Kostis
John B
JB
Simpson
Lara M
LM
Black
Henry R
HR
Cushman
William C
WC
Einhorn
Paula T
PT
Farber
Michael A
MA
Ford
Charles E
CE
Levy
Daniel
D
Massie
Barry M
BM
Nawaz
Shah
S
D000317:Adrenergic alpha-Antagonists / Q000627:therapeutic use; D000368:Aged; D017311:Amlodipine / Q000627:therapeutic use*; D000959:Antihypertensive Agents / Q000627:therapeutic use; D003327:Coronary Disease / Q000401:mortality / Q000517:prevention & control; D004311:Double-Blind Method; D017292:Doxazosin / Q000627:therapeutic use*; D005260:Female; D006333:Heart Failure / Q000453:epidemiology* / Q000517:prevention & control; D006801:Humans; D006973:Hypertension / Q000150:complications / Q000188:drug therapy / Q000401:mortality / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000453:epidemiology / Q000401:mortality; D054555:National Heart, Lung, and Blood Institute (U.S.); D011379:Prognosis; D018570:Risk Assessment; D013318:Stroke Volume / Q000187:drug effects / Q000502:physiology*; D016019:Survival Analysis; D017741:Survivors; D014481:United States
D000317:Adrenergic alpha-Antagonists; D000959:Antihypertensive Agents; D017311:Amlodipine; D017292:Doxazosin