FDA Approves Heart Drug for Black Patients
By Michelle Meadows
The Food and Drug Administration's approval in June 2005 of a heart failure drug aimed at black patients marks the first time that the agency has approved a drug for a specific racial group. When added to standard heart failure therapy, BiDil dramatically reduces death and hospitalization in blacks.
BiDil is a combination of two older drugs, hydralazine and isosorbide dinitrate. Hydralazine relaxes the arteries so the heart doesn't have to work as hard to push blood through them. Isosorbide dinitrate relaxes both the veins and the arteries. Experts say isosorbide dinitrate may work by releasing nitric oxide at the blood vessel wall, but its effect usually wears off after half a day. Hydralazine may prevent the loss of this effect, but it's not fully known how the two drugs work together. BiDil is taken by mouth and started at a dose of one tablet three times a day, which may be adjusted based on patient tolerance. Adverse side effects may include headaches and dizziness.
The approval of BiDil was based mainly on the results of the African-American Heart Failure Trial (A-HeFT), a study of 1,050 self-identified black patients with severe heart failure who were already being treated with the best available therapy. This study was conducted because two previous studies suggested a benefit of BiDil in black patients, with no evidence of benefit in the white population.
"We followed a trail of evidence which strongly suggested that there were differences between blacks and whites in response to this medicine," says Anne Taylor, M.D., a professor of medicine at the University of Minnesota Medical School and lead investigator of A-HeFT. "If researchers see differences in disease patterns between population groups, the cause of those differences should be investigated. Differences may be related to environmental, social, lifestyle, or genetic factors or to interactions among all of these factors."
In addition to receiving either BiDil or an inactive substance (placebo), most of the people in the A-HeFT trial also received the current standard therapy for heart failure--a diuretic, an angiotensin-converting enzyme inhibitor or an angiotensin receptor blocker, and a beta blocker. The trial was conducted at more than 160 sites in the United States. Participants included people ages 18 and older who had a heart failure diagnosis for at least three months. In people with heart failure, the heart is weakened and doesn't pump enough blood. Heart failure can be caused by heart attacks, high blood pressure, infections, and other conditions that can damage the heart muscle.
Patients on BiDil experienced a 43 percent reduction in death and a 39 percent decrease in hospitalization for heart failure, compared with patients who took a placebo. Patients taking BiDil also experienced a decrease of their heart failure symptoms, notably shortness of breath and extreme fatigue. The results were so favorable that the trial was stopped early so that all the participants could take BiDil. Study results of A-HeFT, which ran from June 2001 to July 2004, were published in the November 2004 issue of The New England Journal of Medicine. The trial was cosponsored by the Association of Black Cardiologists Inc. of Atlanta and NitroMed Inc. of Lexington, Mass., which manufactures BiDil.
"Because patients who were already on standard medication saw such a dramatic difference with BiDil, the data suggest that some additional mechanism of the disease was treated by the combination," says Taylor. One hypothesis is that heart failure in blacks may be associated with a deficit in the production of nitric oxide, and BiDil may work by replenishing nitric oxide to the vascular tissue. "This is just a hypothesis, and this trial doesn't prove or disprove it," Taylor says. "What this trial shows is efficacy, and we need to go back and carry out more research to try to understand why it works."
The approval of BiDil is especially significant because blacks between ages 45 and 64 are 2.5 times more likely to die from heart failure than whites in the same age range, according to the Centers for Disease Control and Prevention. Blacks also present with heart failure and die from the disease at an earlier age than whites. Heart failure affects about 5 million Americans, including about 750,000 blacks. There is no cure, and more than half of patients die within five years of diagnosis.
"In BiDil, we now have a treatment that has been shown to save the lives of black heart failure patients, helping a population that is disproportionately burdened by cardiovascular disease," Taylor says.
The differences in health outcomes for blacks are due to many factors. "This includes the prevalence of risk factors, access to care and the availability of insurance, the ability to pay for treatment, the interaction between the physician and patient, where people live, lifestyle factors like smoking and weight," Taylor says. "A single treatment like BiDil is only a piece of the mosaic."
The National Medical Association commended the FDA for the approval of BiDil and expressed its position that a larger clinical trial involving other populations would also be helpful. Taylor says that because results were so positive for those who took BiDil, A-HeFT will stimulate further research on the drug in other populations.
BiDil is a striking example of how a treatment can benefit some patients even if it doesn't help all patients, says Robert Temple, M.D., the FDA's Associate Director for Medical Policy. "The information presented to the FDA clearly showed that blacks suffering from heart failure will now have an additional safe and effective option for treating their condition. In the future, we hope to discover characteristics that identify people of any race who might be helped by BiDil."
