Hydralazine–Isosorbide Dinitrate in African-American Systolic HF Patients

Study Questions:

What is the effectiveness of hydralazine–isosorbide dinitrate (H-ISDN) in African-American patients with systolic heart failure (HF)?


The study cohort included Veterans Affairs (VA) African-American patients with a hospital admission for systolic HF between 2007 and 2013. Inclusion criteria included LV ejection fraction (LVEF) <40%, and receipt of VA medications. Exclusion criteria were contraindications to H-ISDN, creatinine >2.0 mg/dl, or intolerance to angiotensin-converting enzyme inhibitors or angiotensin-receptor blockers (ARBs). The study authors calculated adjusted hazard ratios for patients who received H-ISDN 6 months before admission compared with patients who did not receive H-ISDN, by using inverse probability weighting of propensity scores and a time to death analysis for 18 months of follow-up. They generated propensity scores using patients’ characteristics, LVEF, laboratory values, and hospital characteristics. The primary outcome measure was all-cause mortality in a time-to-event analysis. Patients were followed up for 18 months after index admission to assess mortality.


The final cohort included 5,168 African-American patients with HF (mean age 65.2 years) from 105 VA centers, with 15.2% treated with H-ISDN before index admission. After 18 months, there were 1,275 reported deaths (24.7%). The unadjusted mortality rate was lower in the treated cohort (22.39%) compared with the nontreated cohort (25.08%). The adjusted mortality rate at 18 months was 22.1% for patients receiving H-ISDN treatment and 25.2% for untreated patients (p = 0.009; adjusted hazard ratio, 0.85; 95% confidence interval, 0.73-1.00; p = 0.057). Patients who were taking an ARB or beta-blocker; who had a history of ischemic heart disease, hypertension, or cerebrovascular disease; who were younger; who had lower hemoglobin levels; and who were treated in the South and Midwest were more likely to receive H-ISDN at baseline.


The authors concluded that H-ISDN remains underutilized in African-American patients with HF and reduced EF (HFrEF). They also reported that H-ISDN use was associated with lower mortality rates in African-American patients with HFrEF when controlling for patient selection.


In this study, only 15% of African Americans with systolic HF who were determined as eligible received H-ISDN. Despite this underutilization, the use of H-ISDN was associated with a 15% lower mortality hazard during 18 months of observation post-hospitalization. The findings of this study should, therefore, prompt the health care provider to make greater efforts to utilize H-ISDN in African-American patients with systolic HF.

Clinical Topics: Geriatric Cardiology, Heart Failure and Cardiomyopathies, Prevention, Vascular Medicine, Acute Heart Failure, Chronic Heart Failure, Hypertension

Keywords: Adrenergic beta-Antagonists, African Americans, Angiotensin-Converting Enzyme Inhibitors, Angiotensin Receptor Antagonists, Cerebrovascular Disorders, Creatinine, Geriatrics, Heart Failure, Heart Failure, Systolic, Hemoglobins, Hydralazine, Hypertension, Isosorbide Dinitrate, Myocardial Ischemia, Stroke Volume, Treatment Outcome, Veterans

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