The American Heart Association (AHA) estimates that approximately 6.6 million Americans are affected with chronic angina. For patients who still experience angina attacks despite myocardial revascularization and optimal pharmacotherapy, a new treatment option is available.

The Food & Drug Administration has approved ranolazine (Ranexa, CV Therapeutics) for the treatment of chronic angina. The first in a new class of angina medications called fatty acid oxidation (pFOX) inhibitors, it is indicated for use in combination with the traditional antianginal agents amlodipine, beta-blockers, or nitrates.

Chronic angina is characterized by episodes of chest pain or discomfort caused by inadequate blood flow to the heart muscle. "It is usually triggered by physical exertion," said Mohammed Khan, M.D., department of cardiology, Newark Beth Israel Medical Center, Newark, N.J. "Ranexa appears to work by shifting the fuel source normally used by the stressed heart from fatty acid to glucose, which requires less oxygen to produce the same amount of energy. The result is increased efficiency of oxygen utilization by the heart," he explained.

Ranexa

In a controlled study published in the Journal of the American Medical Association (JAMA) in 2004, patients who had symptomatic chronic angina, despite taking standard antianginal drugs, were randomized to receive ranolazine or placebo. In the ranolazine group, the researchers observed increases in exercise duration and in times to angina and to electrocardiographic ischemia. "These increases did not depend on changes in blood pressure or heart rate," noted lead author Bernard R. Chaitman, M.D., professor of medicine, director of cardiovascular research, St. Louis University School of Medicine. Furthermore, ranolazine reduced angina attacks (and nitroglycerin use) by about one per week compared with placebo (p<0.02). However, the effects on angina frequency and exercise tolerance were found to be considerably smaller in women than in men.

The most commonly reported adverse events associated with ranolazine were dizziness, headache, constipation, and nausea. About 6% of patients discontinued treatment with ranolazine in clinical trials due to an adverse event, compared with 3% receiving placebo.

The package labeling states that ranolazine is contraindicated in patients with preexisting QT prolongation, or in patients taking QT-prolonging drugs (i.e., quinidine, sotalol, or dofetilide). Ranolazine is also contraindicated in patients with hepatic impairment and in patients taking potent or moderately potent CYP3A inhibitors (i.e., ketoconazole, diltiazem, verapamil, or macrolide antibiotics).

"Pharmacists should be fully knowledgeable about these drug interactions and communicate this vital information to their patients in order to ensure safe use of Ranexa," said Claude Clermont, R.Ph., a staff pharmacist at Newark Beth Israel Medical Center.

According to its maker, ranolazine should be initiated at 500 mg twice daily and increased to 1000 mg twice daily, as needed, based on clinical symptoms. No dosage adjustment is needed in patients with congestive heart failure or diabetes. The manufacturer recommends that, in patients receiving ranolazine, both baseline and follow-up electrocardiograms should be obtained to evaluate the effects on QT interval.

The company expects to launch ranolazine by the end of March.

THE AUTHOR is a writer and hospital pharmacist in New Jersey.