Effect of Fixed-Dose Combination of isosorbide dinitrate and hydralazine on all hospitalizations and on 30-day readmission rates in patients with heart failure

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 FDCI/ 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.