NitroMed, Inc. (Lexington, MA), is an emerging research-based pharmaceutical company and the manufacturer of BiDil┬« (isosorbide dinitrate/hydralazine hydrochloride). BiDil was approved by the US Food and Drug Administration (FDA) in June 2005 and is marketed by NitroMed through a dedicated sales force. The medicine is indicated for the treatment of heart failure (HF) as an adjunct to current standard HF therapy in self-identified black patients to improve survival, prolong time to hospitalization for HF and improve patient-reported functional status. The FDA approval of BiDil was based primarily on the efficacy data from the companyÔÇÖs landmark African American Heart Failure Trial (A-HeFT), as well as the unanimous recommendation for approval from the FDA Cardiovascular and Renal Drugs Advisory Committee.
A-HeFT - co-sponsored by NitroMed and the Association of Black Cardiologists, Inc. - was the first study conducted in a HF population in which all of the participants identified themselves as black. This phase 3 trial commenced in June 2001 and evaluated the effects of BiDil in black patients when taken in addition to current standard HF therapies. After a unanimous recommendation from the independent A-HeFT Data and Safety Monitoring Board (DSMB) and Steering Committee in July 2004, A-HeFT was halted early due to a significant survival benefit seen with the drug.
In A-HeFT, most patients received (in addition to BiDil or placebo) a loop diuretic, an angiotensin converting enzyme (ACE) inhibitor or an angiotensin -2 receptor blocker (ARB) and a beta-blocker, and many also received a cardiac glycoside or an aldosterone antagonist. Self-identified black patients taking BiDil in addition to current standard HF therapies experienced a significant 43% decrease in the risk of mortality ((P=0.012) absolute mortality rate: BiDil 6.2% versus placebo 10.2%), a 39% reduction in the risk of first hospitalization for HF (P<0.001) (absolute first hospitalization rate: BiDil 16.4% versus placebo 24.4%) and a statistically significant improvement at most time points in response to the Minnesota Living with Heart Failure┬« Questionnaire (MLHF-Q), which is a self-report of the patientÔÇÖs functional status versus patients taking placebo. The results from A-HeFT were presented at the American Heart AssociationÔÇÖs (AHAÔÇÖs) 2004 Scientific Sessions and were published in the November 2004 issue of the New England Journal of Medicine.