The A-HeFT study used a unique composite endpoint of mortality, first hospitalization for heart failure and patient reported functional status in patients receiving BiDil in addition to current standard therapies compared to patients receiving these current therapies plus placebo. Most patients in the trial received, in addition to BiDil or placebo, a loop diuretic, an angiotensin converting enzyme inhibitor or an angiotensin receptor blocker, and a beta-blocker, and many also received a cardiac glycoside and/or an aldosterone antagonist.
A-HeFT was a randomized, double-blind, placebo-controlled study that enrolled 1,050 self-identified African American patients with New York Heart Association (NYHA) class III or IV heart failure at 169 clinical research sites. According to NYHA Classification patients had marked limitation of physical activity (NYHA Class III) or were unable to carry out any physical activity without discomfort (NYHA Class IV).
Participants in A-HeFT were required to be symptomatically stable, while receiving a stable treatment regimen for heart failure at the beginning of the trial, per their physicians. Mean age upon entry into the study was 57 where 60% were male and 40% female. A-HeFT patients were evaluated every three months to assess clinical status and self reported functional status. Follow-up with patients continued throughout their participation in the study, up to a maximum of eighteen months. No patients were lost to follow-up for vital status.
The results of A-HeFT were exceptionally strong. Clinical trial results demonstrated that in the BiDil treatment group versus patients taking placebo, there was: significant improvement in the primary efficacy endpoint, a composite score of all-cause mortality, first hospitalization for heart failure, and patient-reported functional status (responses to the Minnesota Living With Heart Failure® Questionnaire), composite score: -0.16 for BiDil vs. -0.47 for placebo (P>.021).1
Important information about BiDil®
(isosorbide dinitrate/hydralazine hydrochloride):
INDICATIONS AND USAGE
BiDil is indicated for the treatment of heart failure as an adjunct to standard therapy in self-identified black patients to improve survival, to prolong time to hospitalization for heart failure, and to improve patient-reported functional status. There is little experience in patients with NYHA class IV heart failure. Most patients in the clinical trial supporting effectiveness (A-HeFT) received a loop diuretic, an angiotensin converting enzyme inhibitor or an angiotensin II receptor blocker, and a beta blocker, and many also received a cardiac glycoside or an aldosterone antagonist.
IMPORTANT SAFETY INFORMATION
BiDil is contraindicated in patients who are allergic to organic nitrates.
WARNINGS AND PRECAUTIONS
Augmentation of the vasodilatory effects of isosorbide dinitrate by phosphodiesterase inhibitors such as sildenafil, vardenafil, or tadalafil could result in severe hypotension. The time course and dose dependence of this interaction have not been studied. Reasonable supportive care should consist of those measures used to treat a nitrate overdose with elevation of the extremities and central volume expansion.
Treatment with hydralazine hydrochloride may produce a clinical picture simulating systemic lupus erythematosus including glomerulonephritis. If systemic lupus erythematosus-like symptoms occur in patients treated with BiDil, discontinuation of BiDil should be considered only after a thorough benefit-to-risk assessment. Symptoms and signs of systemic lupus erythematosus usually regress when hydralazine hydrochloride is discontinued but residua have been detected many years later. Long-term treatment with steroids may be necessary.
Symptomatic hypotension, particularly with upright posture, may occur with even small doses of BiDil. BiDil should be used with caution in patients who may be volume depleted or who are already hypotensive.
Hydralazine hydrochloride can cause tachycardia potentially leading to myocardial ischemia and angina attacks. Careful clinical and hemodynamic monitoring is recommended when BiDil is administered to patients with acute myocardial infarction to avoid the hazards of hypotension and tachycardia.
Hydralazine hydrochloride has been associated with peripheral neuritis, evidenced by paresthesia, numbness, and tingling, which may be related to an antipyridoxine effect. Pyridoxine should be added to BiDil therapy if such symptoms develop.
Isosorbide dinitrate therapy may aggravate angina associated with hypertrophic cardiomyopathy.
Headache and dizziness were the most frequent adverse events occurring at an incidence greater than 2% in clinical studies compared to placebo. Others included chest pain, asthenia, nausea, bronchitis, hypotension, sinusitis, ventricular tachycardia, palpitations, hyperglycemia, rhinitis, paresthesia, vomiting, amblyopia, hyperlipidemia, and tachycardia.
The full Prescribing Information for BiDil is available here.