Adding the drugs isosorbide dinitrate and hydralazine to conventional therapy for advanced heart failure increases survival and improves quality of life in black patients, according to results of the African-American Heart Failure Trial (dubbed A-HeFT).

Dr. Anne L. Taylor, at the University of Minnesota, Minneapolis, and the A-HeFT investigators chose to restrict their study to black patients because previous studies showed different responses to treatment based on ethnicity.

“We don’t think African-Americans are the only group that would benefit from this therapy,” Taylor told Reuters Health. “Our reason for testing this in African-Americans was that previous data in older trials suggested that it might have particular efficacy in this group. So in order to establish proof-of-concept it made sense to test it in populations where the likelihood of response was highest.”

Their study enrolled 1050 patients self-identified as of African descent with severe heart failure. The participants were already being treated for their condition with drugs that included ACE inhibitors, angiotensin-blockers, beta-blockers, digoxin, spironolactone and diuretics.

The subjects were randomly assigned to receive hydralazine hydrochloride and isosorbide dinitrate, or inactive placebo pills, in addition to their regular therapy.

The trial was terminated early when the survival advantage with active treatment became apparent. After an average follow-up of 10 months, there were 32 deaths (6.2 percent) in the combination-therapy group and 54 (10.2 percent) in the placebo group.

The rate of first hospitalizations for heart failure was reduced by 33 percent by active treatment.

Also, quality of life scores measured with a standard questionnaire also improved more in the isosorbide/hydralazine group.

The findings appear in the New England Journal of Medicine for November 11 and have been released early to coincide with presentations at the American Heart Association meeting New Orleans.

Isosorbide is believed to serve as a supplier of nitric oxide, which is involved in the regulation of cardiovascular processes. The antioxidant hydralazine may prolong the effects of isosorbide by slowing the breakdown of nitric oxide, the authors suggest.

In a related editorial, Dr. Joshua M. Hare, a cardiologist at Johns Hopkins in Baltimore, notes, “The administration of a combination of a nitric oxide stimulator and an antioxidant turns out to be an excellent choice and one that addresses fundamental biochemical derangements in the failing cardiovascular system.”

He also points out that the two agents are available individually in generic formulations.

Dr. M. Gregg Bloche, writing in a Perspective article, is not so positive. He claims that the A-HeFT study was “driven in large measure by regulatory and market incentives.”

Bloche, from the Georgetown University Law Center in Washington, DC, writes: “In 1999, NitroMed obtained intellectual-property rights to fixed-dose isosorbide dinitrate and hydralazine and said it would seek FDA approval to market the formulation as a therapy for heart failure in blacks.” If approved by the FDA as a race-specific drug, Bloche says, it will extend drugmaker NitroMed’s intellectual property protection by 13 years.

In response, Taylor noted that the Association of Black Cardiologists, which is dedicated to improving the health of African Americans, was a partner in all aspects of the trial.

Her group’s study “does emphasize the importance of adequate numbers of subgroups in clinical trials to assess where there are differences and where there are no differences,” she continued. “If we don’t have adequate numbers of women or groups of different geographic origin we will not know when those differences are important and when they are not.”

“By following up when differences come to light, one can often learn, as we did in this trial, about additional mechanisms of disease… that allows us to better target our treatment.”

SOURCE: New England Journal of Medicine, November 11, 2004.