ⓘ Isosorbide dinitratehydralazine is a fixed dose combination drug treatment specifically approved by the US FDA to be used to treat self-identified black people ..


ⓘ Isosorbide dinitrate/hydralazine

Isosorbide dinitrate/hydralazine is a fixed dose combination drug treatment specifically approved by the US FDA to be used to treat self-identified black people with congestive heart failure. It is a combination of hydralazine and isosorbide dinitrate. 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.


1. 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.


2. Controversy

The new drug application claiming treatment of a single, self-identified racial group raised a storm of controversy. Some hailed the development of BiDil as a breakthrough for African Americans and a step to addressing the unique health care needs and health disparities of the African American community.

Others who criticized the preliminary studies argued that the original study did not have a significant number of African-American subjects to make the BiDils race specific claims, and that the results of only one clinical trial where African-Americans were tested does not provide a full and comprehensive study. Furthermore, critics argued that self-identified racial identifications from patients as an indicator for race during the trials were not a sufficient categorization method because these self-identifications were socially constructed and have no biological connection to genomic data.

They argued that the trials represented a new form of scientific racism where race, a socially constructed category, would continue to be present in research as a placeholder for genomic identification.

Additionally, some disagreed with the design of the A-HeFT trial because the trial failed to include any non-African American test subjects. The trial was designed to include only African American test subjects, therefore failing to show that BiDil has a greater effectiveness in African Americans than those in other races.

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