Keith Churchwell, M.D., right, and Alastair J.J. Wood, M.D., Ph.D., share a laugh before their talk last week.
photo by Dana Johnson
Seminar takes aim at race-based therapies
Next month, an FDA advisory committee will consider whether to recommend approval of a combination of drugs to treat congestive heart failure specifically in African-Americans.
Is this the dawn of race-based therapy? Two experts at Vanderbilt University Medical Center — Keith B. Churchwell, M.D., and Alastair J.J. Wood, M.B., Ch.B. — have their doubts.
A study of 1,050 African-American patients was halted last year after those who were given the drug combination, called BiDil, plus standard medical therapy were found to have a significantly lower death rate than those receiving standard therapy alone.
“I think our response (to the study) should be healthy skepticism,” said Churchwell, assistant clinical professor of Medicine. The study should be repeated, he added, because no other medical treatment has improved mortality in patients with heart failure.
BiDil is a combination of two vasodilators, isosorbide dinitrate and hydralazine. According to the manufacturer, NitroMed Inc., the drugs may reduce the risk of heart failure by restoring deficient levels of nitric oxide. Some studies suggest that African-Americans are deficient in nitric oxide compared to Caucasians.
The BiDil study, called the African-American Heart Failure Trial, did not include whites, however. As a result, “we have absolutely no evidence that blacks respond differently to this therapy than whites,” said Wood, professor of Medicine and Pharmacology.
Wood and Churchwell spoke last month during a seminar on “race-based therapeutics” sponsored by the Office for Diversity in Medical Education.
Most patients with heart failure die from arrhythmias — abnormal heart rhythms, said Churchwell, a member of the Vanderbilt Page-Campbell Heart Institute. Implantable defibrillators, which deliver an electrical charge to correct abnormal rhythms, have done more than any medical therapy to reduce deaths in heart failure patients, he added.
While BiDil may be appropriate therapy for some patients, a more rational way to identify them is to determine which specific risk factors for heart failure and death — such as poor blood flow in the heart muscle — respond to the therapy, Churchwell continued.
Wood, an internationally known expert on drug metabolism, also said it is unlikely that African-Americans will respond uniformly to BiDil, or any other therapy. That's because genetic variations that affect drug response tend to be distributed as a spectrum across populations.
Identifying these variations potentially may lead to a way to identify patients most likely to respond to a given therapy according to their genetic make-up, and irregardless of “race,” Wood said.
Whether drug companies will support genetic testing is another matter, he added, because they depend on selling their products to the widest possible patient population in order to recoup their research-and-development investment.
Noting that most drugs on the market are effective in only about 25 percent to 40 percent of the patients who take them, Wood said that “drug companies make money sort of the way Heinz made money from ketchup — a lot of the money comes from the ketchup left on the side of the plate.”
“Drug companies certainly don't want to find themselves in the position of identifying these people in advance because if you do, guess what, 60 percent don't take the drug.”