Inder S Anand1, Sithu Win2, Thomas S Rector2, Jay N Cohn2, Anne L Taylor2. 1. From the Medicine Service Line (I.S.A., S.W., J.N.C., A.L.T.) and Research Service Line (T.S.R.), VA Medical Center, Minneapolis, MN (I.S.A., T.S.R.); Department of Medicine, University of Minnesota, Minneapolis (I.S.A., S.W., T.S.R., J.N.C.); and Department of Medicine, Columbia University Medical Center, College of Physicians and Surgeons, New York, NY (A.L.T.). anand001@umn.edu. 2. From the Medicine Service Line (I.S.A., S.W., J.N.C., A.L.T.) and Research Service Line (T.S.R.), VA Medical Center, Minneapolis, MN (I.S.A., T.S.R.); Department of Medicine, University of Minnesota, Minneapolis (I.S.A., S.W., T.S.R., J.N.C.); and Department of Medicine, Columbia University Medical Center, College of Physicians and Surgeons, New York, NY (A.L.T.).
Abstract
BACKGROUND: Fixed-dose combination of isosorbide dinitrate and hydralazine (FDC-I/H) reduced mortality by 43% and death or first hospitalization for heart failure (HF) by 37% in the African-American Heart Failure Trial (A-HeFT). Reduction in mortality makes it difficult to determine the effect on hospitalizations unless the analysis adjusts for death as a competing risk. METHODS AND RESULTS: In A-HeFT, 1050 self-identified black patients with moderate to severe HF were randomized to FDC-I/H or placebo. The effects of FDC-I/H on first and all hospitalizations and 30-day readmission rates were analyzed. Deaths as competing risks were adjusted using Fine-Gray regression and joint models of hospitalizations and mortality. There were 558 all-cause and 251 HF hospitalizations in placebo compared with 435 and 173 hospitalizations in the FDC-I/H group. Adjusting for deaths as a competing risk, the effect of FDC-I/H on the first hospitalization for HF, expressed in hazard ratio (95% confidence interval), was 0.61 (0.47-0.80; P<0.001) and 0.88 (0.72-1.06; P=0.18) on the first all-cause hospitalization. The effect of FDC-I/H on all recurrent hospitalizations for HF was 0.66 (0.52-0.83; P=0.0005), similar to the effect on the first hospitalizations for HF, whereas the effect on all hospitalizations for any cause was 0.75 (0.63-0.91; P=0.003). The 30-day all-cause readmission rate after the first hospitalization for HF was 23.6% (29 of 123) in placebo versus 14.8% (12 of 81) in the FDC-I/H group, but the effect (0.59; 0.30-1.16; P=0.12) in this small subgroup was not significant. CONCLUSIONS: Treatment with FDC-I/H was associated with a substantial reduction in the first and recurrent HF hospitalizations, and in total all-cause hospitalizations, reducing the total burden of costly and distressing hospitalizations. CLINICAL TRIAL REGISTRATION URL: http://www.clinicaltrials.gov. Unique identifier: NCT00047775.
RCT Entities:
BACKGROUND: Fixed-dose combination of isosorbide dinitrate and hydralazine (FDC-I/H) reduced mortality by 43% and death or first hospitalization for heart failure (HF) by 37% in the African-American Heart Failure Trial (A-HeFT). Reduction in mortality makes it difficult to determine the effect on hospitalizations unless the analysis adjusts for death as a competing risk. METHODS AND RESULTS: In A-HeFT, 1050 self-identified black patients with moderate to severe HF were randomized to FDC-I/H or placebo. The effects of FDC-I/H on first and all hospitalizations and 30-day readmission rates were analyzed. Deaths as competing risks were adjusted using Fine-Gray regression and joint models of hospitalizations and mortality. There were 558 all-cause and 251 HF hospitalizations in placebo compared with 435 and 173 hospitalizations in the FDC-I/H group. Adjusting for deaths as a competing risk, the effect of FDC-I/H on the first hospitalization for HF, expressed in hazard ratio (95% confidence interval), was 0.61 (0.47-0.80; P<0.001) and 0.88 (0.72-1.06; P=0.18) on the first all-cause hospitalization. The effect of FDC-I/H on all recurrent hospitalizations for HF was 0.66 (0.52-0.83; P=0.0005), similar to the effect on the first hospitalizations for HF, whereas the effect on all hospitalizations for any cause was 0.75 (0.63-0.91; P=0.003). The 30-day all-cause readmission rate after the first hospitalization for HF was 23.6% (29 of 123) in placebo versus 14.8% (12 of 81) in the FDC-I/H group, but the effect (0.59; 0.30-1.16; P=0.12) in this small subgroup was not significant. CONCLUSIONS: Treatment with FDC-I/H was associated with a substantial reduction in the first and recurrent HF hospitalizations, and in total all-cause hospitalizations, reducing the total burden of costly and distressing hospitalizations. CLINICAL TRIAL REGISTRATION URL: http://www.clinicaltrials.gov. Unique identifier: NCT00047775.
Authors: Pardeep S Jhund; Piotr Ponikowski; Kieran F Docherty; Samvel B Gasparyan; Michael Böhm; Chern-En Chiang; Akshay S Desai; Jonathon Howlett; Masafumi Kitakaze; Mark C Petrie; Subodh Verma; Olof Bengtsson; Anna-Maria Langkilde; Mikaela Sjöstrand; Silvio E Inzucchi; Lars Køber; Mikhail N Kosiborod; Felipe A Martinez; Marc S Sabatine; Scott D Solomon; John J V McMurray Journal: Circulation Date: 2021-04-09 Impact factor: 29.690
Authors: Meaghan Lunney; Marinella Ruospo; Patrizia Natale; Robert R Quinn; Paul E Ronksley; Ioannis Konstantinidis; Suetonia C Palmer; Marcello Tonelli; Giovanni Fm Strippoli; Pietro Ravani Journal: Cochrane Database Syst Rev Date: 2020-02-27