Isosorbide dinitrate/hydralazine

Isosorbide dinitrate/hydralazine is a fixed dose combination drug treatment specifically indicated for African Americans with congestive heart failure. It is a combination of hydralazine (an antihypertensive) and isosorbide dinitrate (a vasodilator). It is the first race-based prescription drug in the United States.

The combination preparation is marketed in the United States under the trade name BiDil by Arbor Pharmaceuticals, Inc. which purchased the rights to market the drug in December 2011 from NitroMed.

Background
From 1980 to 1985 Dr. Jay Cohn of the University of Minnesota led a clinical trial in collaboration with the US Veterans Administration called the Vasodilator-Heart Failure Trial (V-HeFT I) that tested whether the combination of Isosorbide dinitrate and hydralazine increased survival in patients with heart failure; the results were promising and the study was followed by V-HeFT II, which tested the combination against enalapril. In the meantime, Cohn applied for a patent on the combination treatment, which issued in 1989 as US Patent 4868179. Cohn licensed the patent to a company called Medco, and Medco spent the early 1990s preparing a New Drug Application (NDA) to get the FDA to approve BiDil on the basis of the V-HeFT trials. However, the trials were not designed to support an NDA, and in 1997 the FDA rejected the application because it did not have enough statistical power to show whether the combination really worked.

Cohn re-analyzed the data and found a signal that the drug combination appeared to work better in self-identified African-Americans in the V-HeFT trial, and published a paper on that work, and filed a new patent on the use of BiDil in "black" patients. It had already been known that African-Americans with congestive heart failure (CHF) respond less effectively to conventional CHF treatments (particularly ACE inhibitors) than caucasians.

The new patent and the old patent were licensed to a company called NitroMed, which ran a clinical called the African-American Heart Failure Trial (A-HeFT), the results of which were published in 2004 in the New England Journal of Medicine. The clinical trial was stopped early because the drug worked so well; it reduced mortality by 43%, reduced hospitalizations by 39%, and improved quality of life markers in African-American patients with CHF.

On the basis of A-HeFT, the FDA approved BiDil in June 2005. In 2006, the Heart Failure Society of America included the use of the fixed dose combination of isosorbide dinitrate/hydralazine as the standard of care in the treatment of heart failure in blacks.

Though BiDil must still be taken three times daily, as must the component pills in separate ISDN-H treatment, the reduction in pill burden has been suggested to improve compliance, and thus a better medical outcome.

Controversy
The new drug application claiming treatment of a single, self-identified racial group raised a storm of controversy, with some hailing a breakthrough for African-Americans, and others decrying a new form of scientific racism. Additionally, some disagreed with the design of the A-HeFT trial because the trial failed to include any non-African American test subjects.