Effect of Fixed-Dose Combination of Isosorbide Dinitrate and Hydralazine on All Hospitalizations and on 30-Day Readmission Rates in Patients With Heart Failure

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.(Circ Heart Fail. 2014;7:759-765.)Key Words: heart failure ◼ hospitalization ◼ isosorbide dinitrate Received February 28, 2014; accepted June 13, 2014. 7 trials found that the pure heart rate-slowing agent ivabradine and the mineralocorticoid receptor antagonist eplerenone reduced all HF hospitalizations.Recently, there has been great interest in reducing all-cause readmissions that occur <30 days after a hospitalization for worsening HF. 10,11 These data are used to determine Medicare payments to hospitals for inpatient HF care, and hospitals with above average readmission rates are being financially penalized.1 Whether 30-day readmission rates can be reduced by therapy is unclear, and most clinical trials have not reported the effects of treatments on 30-day all-cause readmission rates. Public measures of 30-day readmission rates count all readmissions, not only those for HF. However, most 30-day readmissions are not because of worsening HF and may not be responsive to treatments for HF. 10,12 We used several statistical methods that take into account the effects of the competing risk of death and correlation of recurrent ...

Outcomes in patients hospitalized for heart failure and chronic obstructive pulmonary disease: differences in clinical profile and treatment between 2002 and 2009

“…Our results are similar to those of the Worcester Heart Failure Study, where patients with acute HF and COPD had a higher risk of all‐cause death at 1‐ and 5‐year follow‐up. The main reason was related to greater severity of cardiovascular and respiratory disease or to repeated readmissions for HF and/or exacerbations of COPD (possible reasons for no response to HF treatment) . Other proposed explanations were a lower rate of prescriptions of drugs for HF and an older population with a higher incidence of HF with preserved LVEF in whom to date the efficacy of long‐term treatment on clinical events has not been demonstrated.…”

Underuse of hydralazine and isosorbide dinitrate for heart failure in patients of African ancestry: a cross‐European survey

“…1 Annual HF mortality rates vary considerably across populations, with an average of 17%. [1][2][3]5,7,[10][11][12]14,15,[21][22][23][24][25][26] The EU (national) data on mortality of AA with HF are not available. [1][2][3]5,7,[10][11][12]14,15,[21][22][23][24][25][26] The EU (national) data on mortality of AA with HF are not available.…”

“…Data from the Duke Databank of Cardiovascular Disease 26 indicated adjusted mortality rates for HF in AA of 12% at 1 year and 49% at 5 years. 2,5,7,8,[10][11][12][13][14][15]18,22,23 After H + ISDN treatment in Vasodilator-Heart Failure Trial I (only AA men), the annual mortality rate of HFrEF was 9.7 vs. 17.3% without receiving this therapy, 10 and in A-HeFT (AA men and women) using fixed combination H-ISDN, this was respectively 6.2 vs. 10.2%. 22 HF is a heterogeneous clinical entity, with a prominent distinction between patients with reduced ejection fraction (HFrEF, broadly corresponding to systolic HF) with usually a dilated left ventricular cavity size, occurring in around half of all HF patients, or preserved (HFpEF) left ventricular ejection fraction with usually a normal left ventricular cavity and concentric hypertrophy.…”

“…In AA patients randomized to H + ISDN, the annual mortality ratio was 9.7% compared with 17.3% with placebo (À44%; P < 0.05), without significant difference in European patients. 5,11,12 Although American as well as European guidelines advise H and ISDN for self-described AA patients with New York Heart Association Class III-IV HF and reduced ejection fraction, 2,5,[13][14][15] recent American studies have indicated that doctors do not prescribe this life-saving therapy to the majority of eligible hospitalized or outpatient AA patients. 11 In addition, a 33% relative reduction in the rate of first hospitalization for HF (16 vs.…”

Practical approaches for the treatment of chronic heart failure: Frequently asked questions, overlooked points and controversial issues in current clinical practice

“…Çavuşoğlu et al Practical approaches for the treatment of chronic heart failure fects of adding H-ISDN to the current ACEI/ARB therapy are not clear in other American populations (20,21).…”