In a controversial move, the Food & Drug Administration notified manufacturer NitroMed Inc., Lexington, Mass., in June, that its lead drug, BiDil (isosorbide dinitrate/ hydralazine), has been approved for the treatment of heart failure in African-Americans.
"In BiDil, we now have a new treatment ... helping a population that is disproportionately burdened by cardiovascular disease," said Anne Taylor, M.D., associate dean for faculty affairs, professor of medicine, University of Minnesota Medical School, and a lead investigator in the clinical trial of BiDil. "African-Americans between the ages of 45 and 64 are 2.5 times more likely to die prematurely from heart failure than are their non-Black counterparts," she said.
In 2001, NitroMed began the African-American Heart Failure Trial (A-HeFT), consisting of 1,050 self-identified Blacks with severe heart failure who received treatment with BiDil along with other standard cardiovascular therapy. The results of A-HeFT, presented at the American Heart Association annual meeting last year, showed an impressive 43% reduction in all-cause mortality and a 39% reduction in risk of first hospitalization for heart failure compared with placebo. Due to the considerable survival benefit seen with BiDil, the trial was halted early, in June 2004.
Normally, the effect of isosorbide wears off quickly, but animal studies have shown that hydralazine may help prevent this loss of effect and mitigate tolerance to nitrates, perhaps through its antioxidative properties.
"While the findings of A-HeFT are impressive, it is important to remember that the benefits of BiDil were seen in combination with other cardiovascular medications," Howard explained.
The most frequently reported adverse reactions in the trial included headache, dizziness, chest pain, asthenia, nausea, bronchitis, and hypotension. Product labeling states that the incidence of headache tends to lessen with continued dosing. BiDil is contraindicated in patients who are allergic to organic nitrates, and the company warns that augmentation of the vasodilatory effects of isosorbide dinitrate by phosphodiesterase inhibitor drugs could result in severe hypotension.
BiDil may cause symptomatic hypotension and, therefore, should be used with caution in volume-depleted or hypotensive patients.
BiDil's approval "is a striking example of how a treatment can benefit some patients even if it does not help all patients," said Robert Temple, M.D., director of FDA's Office of Medical Policy in a recent "Talk Paper" from the agency. "In the future, we hope to discover characteristics that identify people of any race who might be helped by BiDil," he added.
BiDil will be priced at $1.80 per tablet. NitroMed also plans to implement a patient assistance progam to ensure the medication is available to those who need it regardless of income level or health insurance status.