Heart drug seen aiding blacks

NEW ORLEANS -- New data released yesterday indicate that a drug developed by a Lexington biotech company reduced deaths dramatically in African-American heart patients, a finding that stoked a vigorous debate over the potential of using race as a basis for prescribing medications.

The research, published online by The New England Journal of Medicine and announced at the nation's premier gathering of heart specialists, could have immediate implications for the treatment of African-Americans, who are substantially more likely to suffer from cardiovascular disease than other racial and ethnic groups.

The pill tested in the study is made by NitroMed of Lexington and consists of isosorbide dinitrate and hydralazine, long available separately as generic drugs for the treatment of high blood pressure. And while NitroMed has said it is preparing to seek federal approval to sell its pill, a leading cardiologist predicted that some doctors may not wait for the new combination to come onto the market.

Dr. Raymond J. Gibbons, a Mayo Clinic cardiologist, said that "time will tell" how many physicians are sufficiently intrigued by the findings to begin prescribing the two generic pills, not widely used in the past. But Gibbons said using them could prove challenging for doctors who would not be certain how much of each medicine to give.

"We haven't been using these generics enough to know how much of a problem adjusting dose is," Gibbons said. "But I'm sure we'll have a whole bunch of people with more experience doing that soon."

A quarter of a century ago, doctors tested the drugs that are the foundation of the new pill, which will be marketed as BiDil, in a multiracial group of veterans. At that time, the researchers concluded that other medications did a better job of controlling heart disease.

But in the intervening years, cardiologists said, much was learned both about the intricacies of cardiovascular disease and the precise benefits of different heart drugs. At the same time, scientists examined the earlier study more closely and noticed that the generic pills appeared to help the African-American veterans.

"It led someone to go back and say, 'Aha, we need to take another look at this,' " said Dr. Anne L. Taylor of the University of Minnesota, who presided over the human trials of BiDil and presented the findings yesterday at American Heart Association Scientific Sessions 2004.

The new study included 1,050 black men and women with heart failure and found that patients who received BiDil were 43 percent less likely to die than patients receiving a placebo and 33 percent less likely to spend time in a hospital. Researchers monitored the patients for an average of 10 months and for as long as a year and a half. Patients took the pill as part of their broader regimen of treatment, which typically included other cardiovascular medications.

The results were so persuasive that the study was stopped early last summer, an ethical requirement when a clinical trial proves overwhelmingly positive or negative.

Scientists contend the medication works by improving the ability of patients to use nitric oxide, which helps the heart pump more efficiently and relaxes blood vessels, thus reducing blood pressure. Taylor said research has shown that African-Americans experience particular difficulty absorbing nitric oxide, which could provide one explanation for their higher incidence of heart disease.

The study emerges against a backdrop of both historical concerns about the conduct of scientific experiments and forward-looking research into the tailoring of medications to suit the specific genetic and lifestyle profiles of patients. The study also raised worries about limiting a drug trial to a single racial group.

"It seems to me at times you can't win," said Dr. Augustus Grant, a past president of the Association of Black Cardiologists. "Very often it's complained that drugs aren't adequately tested in African-Americans."

After years of failing to adequately include blacks, Hispanics, and women in medical studies, researchers have been directed by federal regulators to make an effort to be more inclusive.

So restricting a study to one racial group, in this case African-Americans, "is politically a difficult thing," said Dr. Timothy Gardner, a University of Pennsylvania surgery professor.

But Gibbons hailed the study as "an admirable attempt" to target a treatment to patients disproportionately affected by heart disease.

Other specialists said that it could open the way to future studies examining the benefits of medicines among specific groups of patients. "Any good clinical investigator who sees an important trend," Grant said, "will follow that trend where it leads."

Stephen Smith can be reached at stsmith@globe.com.