B-A-HEF

Bi-treatment with hydralazine/nitrates versus placebo in Africans with Acute Heart Failure (B-E-HAF)

A prospective, placebo-controlled, double-blind, randomized study to compare treatment with Hydralazine-Isosorbide–Dinitrate (HYIS) versus placebo on top of standard care in African patients admitted with Acute Heart Failure (AHF) and left ventricular dysfunction. The primary objective of this study is to investigate the effect of the combination of hydralazine/isosorbide dinitrate (hyis) on the rate of death or re-admission for heart failure during 24 weeks of therapy in African patients with acute heart failure.

Secondary Objectives

  • To evaluate the effect of HYIS versus placebo on:
  • Change in symptoms of heart failure from baseline to 7 days post-randomization or discharge, as assessed by dyspnea severity and global well being on a VAS scale.
  • Change in systolic blood pressure from baseline to 7 days post-randomization or discharge, and at 8 weeks and 24 weeks post-randomization.
  • Functional status assessed by 6-minute walk at 7 days post-randomization or discharge, and at 8 weeks and 24 weeks post-randomization.
  • Changes in serum creatinine, BUN, and estimated glomerular filtration rate (eGFR) from baseline to 7 days post-randomization or discharge, and at 24 weeks post-randomization.
  • Change in left ventricular dimensions and LVEF from baseline to 24 weeks post-randomization.

Background and Rationale

The use of different medications such as ACEi and hydralazine/nitrates has never been examined in patients admitted with AHF. All studies demonstrating the beneficial effects of these drugs were performed in patients with chronic heart failure. Previous studies have shown that the administration of ACEi in African Americans with chronic heart failure is less effective and not superior to combined treatment with hydralazine/isosorbide dinitrate. A recent striking re-analysis of the SOLVD study showed no effect of enalapril as compared to placebo on death, HF hospitalization and blood pressure reduction in African Americans.

The V-HeFT-1 study compared the effect of a fixed combination of hydralazine and nitrates to placebo in patients with chronic heart failure. The African American Heart Failure Trial (A-HeFT) established the benefit of adjunctive administration of isosorbide dinitrate/hydralazine (ISD N/HYD) in addition to standard therapy for African American patients with symptomatic heart failure. The risk of death was reduced by 43%, the need for first hospitalization was reduced by 33%, and markers of quality of life were improved.

The THESUS registry has shown a high prevalence of hypertension with left ventricular systolic dysfunction (hypertensive heart failure) and dilated cardiomyopathy as a cause of acute heart failure in all participating 9 African countries. Despite the encouraging results of V-HEFT II and A-HeFT, patients in Africa are rarely treated with this combination therapy as the fixed combination (BiDil®) is unavailable in Africa. There is uncertainty if the combination of hydralazine and isosorbide dinitrate, available as generic agents, is beneficial in Africans and many physicians in Africa are not aware of the outcome of those studies published in high impact factor journals often not available to local doctors.

Performing a multi-centre study in Africa could confirm data obtained in African Americans, create awareness for this promising combination treatment, and extend the use of the medication to patients with acute heart failure.

Professor Karen Sliwa is the principle investigator for this prospective, multi-centre, randomized double blind study in 10 African countries.  

This study is funded by African Heart Initiative.