Effect of Fixed-Dose Combination of Isosorbide Dinitrate and Hydralazine on All Hospitalizations and on 30-day Readmission Rates in Patients with Heart Failure: Results from the A-HeFT Trial
Background—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 to 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 [HR (95% CI)] 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 to 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% (29/123) in placebo versus 14.8% (12/81) in FDC-I/H group, but the effect [0.59 (0.30 to 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 heart failure 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.
- Received February 28, 2014.
- Accepted June 13, 2014.