Drug for Only Blacks Stirs Hope, Concern

A new heart drug that targets African Americans reduced deaths from advanced heart failure by 43% and reduced hospitalizations by a third, setting the stage for it to become the first drug approved for only one racial group.

Although many cardiologists Monday hailed the findings because blacks die from heart failure at twice the rate of whites, some geneticists were concerned, arguing that racial categories were an inappropriate way to guide medical treatment.

There might be a genetic predisposition that makes the drug effective, but that predisposition is not necessarily related to race, critics say.

“It’s great that this is showing such promise to treat heart failure,” said ethicist Jonathan Kahn of Hamline University School of Law in Minnesota. “But it is extremely unfortunate that the packaging has been associated with race. All you can tell from the data is that [the drug] works against heart failure. The patients happened to be black, but you can’t make any claims based on the data.”

But many scientists also hailed the study, which was co-sponsored by the Assn. of Black Cardiologists.

“This is excellent news for African Americans with heart failure, who have always fared worse than the general population,” said Dr. Karol E. Watson of UCLA, who was not involved in the study. “Racial profiling is typically used to withhold therapy.... When it is used as a positive to improve therapy, then I don’t have a problem.”

The drug in question is BiDil, manufactured by NitroMed Inc. of Lexington, Mass. BiDil is a combination of two heart drugs now distributed generically, isosorbide dinitrate and hydralazine. Isosorbide dinitrate is thought to stimulate the production of nitric oxide, which has a variety of beneficial effects on the heart. Hydralazine is used for treating high blood pressure.

The results were reported Monday at a New Orleans meeting of the American Heart Assn. and will be published this week in the New England Journal of Medicine.

The report represents the culmination of 30 years of work by Dr. Jay N. Cohn of the University of Minnesota, who was the first to promote the idea of combining the two drugs.

Cohn organized an initial trial, conducted in the 1980s, in which the two drugs were compared against the family of heart drugs called angiotensin-converting enzyme inhibitors in a broad cross-section of the population.

That study found that the ACE inhibitors worked better. The combination of isosorbide dinitrate and hydralazine provided some benefit, but not enough to justify approval, according to the Food and Drug Administration.

When Cohn reanalyzed the data and stratified the results by race, however, it appeared that the drug provided greater benefits for blacks. That was an intriguing finding because, even though heart failure affects 5 million Americans, blacks are 2 1/2 times more likely to suffer from it. The disease occurs when heart muscles weaken, interfering with pumping and allowing fluids to back up into the lungs, causing shortness of breath.

Spurred by these findings, Cohn and his colleagues organized a new study of the two drugs in 1,050 patients self-identified as black. Half received the drugs in conjunction with normal therapy for heart failure, and half received only conventional therapy. In both cases, subjects were given an ACE inhibitor.

The results were so striking that the study was terminated prematurely in July. Over the two years of the study, 6.2% of the patients given BiDil died, compared with 10.2% of those given the standard treatment. First hospitalizations for heart failure were observed in 16.4% of those receiving BiDil, compared with 24.4% of those receiving conventional therapy.

“We discovered that patients were indeed living longer and that their incidence of death was dramatically reduced,” said Dr. Clyde Yancy of the University of Texas Southwestern Medical Center, a study coauthor.

“The publication of this trial’s results virtually ensures FDA approval,” Dr. M. Gregg Bloche of Johns Hopkins University wrote in an editorial that will accompany the report in the New England Journal of Medicine.

NitroMed said it would submit the results to the FDA this year and hoped to begin marketing the drug in 2005. The FDA has indicated that it would approve race-based labeling. Physicians could still prescribe the drug to other racial groups, but critics said that insurance companies might not pay for it.

Such labeling will be unprecedented, but physicians are aware that many drugs have different effects in whites and blacks. The ACE inhibitors, for example, are generally agreed to be less effective in blacks. A recent report in the journal Nature Genetics listed 29 drugs that were known to have different efficacies in the two races.

But many geneticists believe that race is an artificial construct that says very little about differences among people. Studies often find a greater genetic variability between individuals within a specific race than between those of different races.

Given those results, race becomes a “blunt instrument” for making prescribing decisions, according to Dr. Jim Kennedy, a spokesman for the Royal College of General Practitioners in Britain. But, he added, “it’s better than nothing.”

Even strong proponents of BiDil were uneasy about the labeling. “I don’t understand why they would have to approve it for black people,” said Dr. Sally Satel, author of “PC MD: How Political Correctness Is Corrupting Medicine.” “They could just approve it and say it is a first-line drug in blacks and a second-line drug in others,” she said.

Kahn, the ethicist, said the label sent the wrong message in a society where blacks often received inadequate medical treatment. “It lends credence to the idea that blacks and whites are genetically different,” he said. “And it’s a short step from saying blacks are genetically different to saying they are genetically inferior.”

Some say the potential labeling may be less a reflection of racial differences than of financial incentives. Many critics view the proposed labeling as a clever strategy by NitroMed to extend the patent on drugs that are widely available in generic form -- and to obtain a premium price for them.

Cohn holds a patent on using the combination to treat all races, but that patent expires in 2007. NitroMed has a patent on using it to treat blacks, and that patent is good until 2020, preventing anyone from bringing out a generic version of the combination pill before then. Physicians could, however, prescribe the two drugs individually to either blacks or whites. A dose of the generic drugs costs about 44 cents.

BiDil has not been tested in whites in conjunction with ACE inhibitors, and experts argued that it might be effective in them as well. But because the drug’s patent for general use is set to expire, it seems unlikely that any company would fund such a trial.