Select your localized edition:

Close ×

More Ways to Connect

Discover one of our 28 local entrepreneurial communities »

Be the first to know as we launch in new countries and markets around the globe.

Interested in bringing MIT Technology Review to your local market?

MIT Technology ReviewMIT Technology Review - logo


Unsupported browser: Your browser does not meet modern web standards. See how it scores »

{ action.text }

“A Different Disease”

The drug that became known as BiDil didn’t start out as a racially targeted medicine. The story of how it came to be the center of the debate on race-based medicines is long and convoluted. It is also a story that, in some ways, reflects the frustration of trying to find more-effective treatments for heart failure, a disease that has reached epidemic proportions: with around 500,000 new cases diagnosed every year, it is the only major form of cardiovascular disease on the rise, and annual death rates have more than doubled since 1979. While the pharmaceutical industry has developed a series of new drugs for the disease over the last decade or so, less than 50 percent of patients survive more than five years.

Within the field of heart failure medicine, Jay Cohn, the developer of BiDil and inventor on a patent for its use in treating heart failure in African Americans, is a towering figure. A professor of cardiology at the University of Minnesota and director of its Rasmussen Center for Cardiovascular Disease Prevention, Cohn was a founder of the Heart Failure Society of America and has participated in a number of the field’s landmark clinical trials of new treatments.

In the 1970s, Cohn was a young, ambitious cardiologist looking for some way to offer hope to his heart failure patients. At the time, there were no drugs that could significantly change the course of heart failure, he recalls. Patients were given digitalis, a 200-year-old medicine used to strengthen the contractions of the heart, and diuretics to alleviate the buildup of fluids, but neither of these drugs averted the fate of the patients. “You got worse and you died,” says Cohn.

To change that grim prognosis, Cohn and his colleagues began testing intravenous medications to relax patients’ arteries, believing that opening up the arteries would reduce the work the heart had to do. By 1980, Cohn and his partners had come up with an oral treatment that combined a pair of compounds, one that dilated blood vessels and another that boosted levels of nitric oxide, which is thought to be a natural vasodilator in the body. The cardiologists then began a 640-patient study at more than a dozen U.S. Veterans Administration hospitals around the country to evaluate the effects of the vasodilator therapy on those suffering from heart failure.

The results of the V.A. studies showed that patients appeared to gain some slight benefit from the drugs in terms of reduced mortality, prompting various cardiologists’ groups, including the American Heart Association, to begin recommending that the combination be given to those who did not respond well to other heart failure treatments. A second trial at the V.A. hospitals was completed in 1991. This time the test compared the two-drug treatment developed by Cohn and his colleagues to the ACE inhibitor enalapril, a newly developed type of vasodilator.

In 1996, Medco Research, a small North Carolina drug firm that had licensed rights to the medicine from Cohn, tried to gain FDA approval for the drug combination, which by then had been packaged as a single pill called BiDil. The FDA advisory panel, however, rejected the application for the heart failure medicine, citing insignificant evidence of its efficacy.

It was soon after FDA rejection that BiDil was reborn as a race-specific drug. In 1999, Cohn and several colleagues went back to the V.A. studies and reanalyzed the data. “To our surprise, blacks dramatically benefited compared to whites,” says Cohn. While Cohn says he suspects BiDil “will work for everyone,” the numbers showed that in whites, on average, the benefit of the drug was marginal – so small that it was statistically insignificant in such a limited sample. But in blacks, the drug combination reduced mortality by 47 percent in the first V.A. study (a finding similar to A-HeFT’s later 43 percent improvement); in the second set of trials done at the V.A. Hospitals, whites responded better to enalapril than to BiDil, but many black patients responded poorly to the ACE inhibitor. For those patients, BiDil appeared to be an effective alternative.

In retrospect, says Cohn, the results shouldn’t have been surprising. At around that time, he points out, other studies suggested ACE inhibitors were less effective in African Americans than in whites, and there was evidence that black and white patients responded differently to drugs for hypertension, the leading cause of heart failure in African Americans. Still, acknowledges Cohn, why BiDil works better in blacks than in whites is something of a mystery. “I don’t pretend to understand all the factors,” he says. “And I don’t suggest it’s a uniform difference. But on average, responses appear to be different.”
One possibility is that the effectiveness of BiDil depends on the etiology of the disease – why patients suffer heart failure in the first place. The disease can be caused by various factors, including previous heart attacks or a history of hypertension. And, suspect some experts, BiDil works best for those patients, whether white or black, who have developed heart failure through hypertension.

If true, that conjecture would help explain the difference, on average, between white and black responses to BiDil. African Americans suffer from high rates of hypertension, and over 50 percent of blacks with heart failure are thought to have it due to histories of high blood pressure. In contrast, most whites, roughly 70 percent, get heart failure due to heart attacks or chronic heart disease. The reason for the high rate of hypertension in blacks remains uncertain. Some studies point to environmental factors, while others seem to implicate specific genetic variants. Muddling the situation even further, according to Yancy, there is some evidence that genetic factors make hypertension more damaging to tissues in black patients than in whites, so that it is, in effect, a more “malignant” condition in African Americans than in whites.

Whatever the underlying reasons, for cardiologists treating patients, says Yancy, “heart failure is a different disease in blacks. It’s different in how it presents itself.” Blacks, he points out, suffer from heart failure at a younger age, and they do not respond as well to hospitalization and treatments. BiDil works in part by addressing deficiencies of nitric oxide, which many African Americans show a reduced ability to utilize, says Yancy.

But if, in fact, BiDil works best for those who develop heart failure because of hypertension, it also could benefit thousands of non–African Americans. And clearly the potential deficiencies of nitric oxide found in some heart failure patients are not strictly limited to blacks. Yancy, for one, says he is “absolutely confident” that BiDil will work for patients other than African Americans. Indeed, says Cohn, ideally BiDil would be given to all those heart failure patients in whom physicians could “identify nitric oxide deficiencies. Unfortunately, there is no simple test.” So for now, race remains the admittedly imperfect screen for those patients.

0 comments about this story. Start the discussion »

Tagged: Biomedicine

Reprints and Permissions | Send feedback to the editor

From the Archives


Introducing MIT Technology Review Insider.

Already a Magazine subscriber?

You're automatically an Insider. It's easy to activate or upgrade your account.

Activate Your Account

Become an Insider

It's the new way to subscribe. Get even more of the tech news, research, and discoveries you crave.

Sign Up

Learn More

Find out why MIT Technology Review Insider is for you and explore your options.

Show Me