FOR THE FIRST TIME, the Food and Drug Administration (FDA) has approved a drug for use in patients of a specific racial group. BiDil was approved last year for the treatment of heart failure in "self-identified black patients," meaning patients who identify themselves as African-American. The FDA called this landmark approval "a step toward the promise of personalized medicine."
BiDil offers a new treatment option for a population at risk for heart failure. Statistics from the Centers for Disease Control and Prevention (CDC) show that African-Americans between ages 45 and 64 are 2.5 times more likely to die from heart failure than whites in the same age range.
The FDA's unusual move was made partly in response to results from the African-American Heart Failure Trial (A-HeFT), according to FDA officials. A-HeFT demonstrated the safety and efficacy of BiDil versus placebo in a study of 1,050 African-American patients with moderate-to-severe symptomatic heart failure (New York Heart Association [NYHA] Class III to IV, with left ventricular ejection fraction less than or equal to 35%) receiving standard treatment. An ejection fraction is the percentage of blood ejected from the ventricle with each heart beat. A normal ejection fraction is greater than 65%. In heart failure, this is obviously decreased. See the New York Heart Association classification of heart failure for more information.
In the study, mortality dropped 43% and hospitalization for heart failure was reduced by 39%. Interestingly, analysis of a previous study that included heart failure patients of other racial or ethnic groups showed that the components of BiDil didn't improve survival for other ethnicities, but it did seem to help African-Americans.
Effective combination
BiDil is a combination drug containing hydralazine and isosorbide dinitrate, two drugs that aren't approved by the FDA to treat heart failure by themselves. Hydralazine is a medication for high blood pressure; it relaxes the arteries and decreases the work of the heart. Isosorbide dinitrate, an antianginal agent, relaxes the veins as well as the arteries. It causes the endothelial lining of the blood vessel to release nitric oxide, producing vascular smooth muscle relaxation. Its effects usually dissipate quickly. Adding hydralazine is thought to help prolong nitric oxide's effects.
Each tablet contains 20 mg of isosorbide dinitrate and 37.5 mg of hydralazine. Initially, patients are given a dosage of one tablet three times a day. The maximum dosage shouldn't exceed two tablets three times a day.
Target population
You may wonder why the combination of drugs is effective for treating heart failure in African-Americans. The company that markets BiDil, NitroMed, Inc., Lexington, Mass., believes that a deficiency of nitric oxide is associated with heart failure in African-Americans and that BiDil works because it's intended to boost the level of nitric oxide. (Nitric oxide insufficiency may also explain why African-American patients with high blood pressure don't respond as well as other populations to monotherapy with an angiotensin-converting enzyme inhibitor or beta-blocker.)
Based on CDC data, NitroMed estimates that 750,000 African-Americans have been diagnosed with heart failure and that the number may grow to 900,000 by 2010.
Safety comes first
Patients who are allergic to organic nitrates shouldn't take BiDil. For other patients, adverse effects appear to be few and not severe. The most common adverse effects are headache and dizziness. Slowly and cautiously titrating the drug to the maximum tolerated dosage may minimize these symptoms. Patients can take acetaminophen for the headache; the symptoms should ease after a couple of weeks.
To date, no one has done a formal assessment of drug-drug interactions of BiDil. Tell a patient who's taking BiDil to report any unusual symptoms to his primary care provider promptly. BiDil's prescribing information cautions against using BiDil with phosphodiesterase-5 inhibitors, such as sildenafil (Viagra), vardenafil (Levitra), and tadalafil (Cialis). Doing so could cause a rapid, severe drop in blood pressure.
Advise patients who are taking BiDil and a medication for high blood pressure at the same time that they may be at increased risk of hypotension. In certain patients, symptomatic hypotension may occur even with low doses of BiDil.
Treatment with hydralazine can produce symptoms similar to systemic lupus erythematosus, including glomerulonephritis (an inflammatory kidney disease). Hydralazine can also cause tachycardia potentially leading to myocardial ischemia and anginal attacks.
Primary care providers must be careful when using BiDil in dehydrated patients. And, caution should be exercised if BiDil is used with a monoamine oxidase inhibitor, such as isocarboxazid (Marplan) or phenelzine (Nardil), or with alcohol.
On the Web
American Heart Association: http://www.americanheart.org, Heart Failure Society of America: http://www.abouthf.org, National Heart, Lung and Blood Institute, National Institutes of Health: http://www.nhlbi.nih.gov
Selected references