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Medication reduces angina attacks, increases exercise capacity for patients with chronic angina

The JAMA Network Journals

Taken with other antianginal medications, the drug ranolazine reduces the frequency of angina and increases exercise capacity in patients with severe chronic angina, according to a study in the January 21 issue of The Journal of the American Medical Association (JAMA).

According to background information in the article, chronic angina is a debilitating illness affecting at least 6.6 million U.S. adults. Patients report limitation of their work and other activities 2 to 3 times more frequently than what is reported by the general population. Despite myocardial revascularization, done largely to prevent angina, and antianginal drugs, up to 26 percent of patients still experience angina attacks.

Bernard R. Chaitman, M.D., of St. Louis University School of Medicine, St. Louis, and colleagues conducted a study to determine whether ranolazine (currently under review by the U.S. Food and Drug Administration) improves the total exercise time of patients who have symptoms of chronic angina and who experience angina and ischemia at low workloads despite taking standard doses of the other antianginal drugs such as atenolol, amlodipine, or diltiazem.

The study, a randomized, double-blind, placebo controlled trial, included 823 adult patients with symptomatic chronic angina who were randomly assigned to receive placebo or 1 of 2 doses of ranolazine. Patients treated at the 118 participating out-patient practice settings in several countries were enrolled in the Combined Assessment of Ranolazine In Stable Angina (CARISA) trial from July 1999 to August 2001 and were followed up through October 31, 2002.

The patients received twice daily placebo or 750 mg or 1000 mg of ranolazine. Treadmill exercise at 12 hours ("trough", or lowest levels of the drug in the bloodstream) and 4 hours (peak, highest levels of the drug in the bloodstream) after dosing was assessed after 2, 6, and 12 weeks of treatment.

"We report the first evidence that ranolazine can reduce both angina frequency and nitroglycerin consumption when added to a standard dose of 1 of 3 frequently prescribed antianginal drugs: atenolol, amlodipine or diltiazem," the authors write. "The decrease in angina attacks vs. placebo were slightly less than 1 per week for those in the 750-mg and somewhat more than 1 per week for those in the 1000-mg ranolazine groups. Exercise duration after 12 weeks of ranolazine therapy increased by 115.6 seconds at trough for those taking ranolazine compared with 91.7 seconds for taking placebo."

The researchers add that ranolazine was without major adverse long-term survival consequences over one to two years of therapy.


(JAMA. 2004;291:309-316. Available post-embargo at

Editor's Note: This study was supported by CV Therapeutics, Inc. Please see JAMA article for authors' financial disclosures.


In an accompanying editorial, Peter Berger, M.D., of Duke University Medical Center, Durham, N.C., discusses the CARISA trial.

"The decision is rarely if ever whether to perform revascularization or administer medical therapy, but rather whether to perform percutaneous coronary intervention (PCI) and administer medical therapy or to administer medical therapy alone. Furthermore, many patients cannot undergo successful percutaneous or surgical revascularization due to anatomic conditions such as severe distal vessel disease, small-branch vessel disease, or other factors."

"Thus, the availability of another effective and apparently safe antianginal medication such as ranolazine is particularly important for such patients with angina who are not candidates for revascularization. Use of ranolazine most likely will influence the frequency and timing with which PCI and coronary artery bypass graft are performed in the far greater number of patients with angina who are suitable for revascularization procedures," he concludes.

(JAMA. 2004;291:365-367. Available post-embargo at

Editor's Note: Dr. Berger has received research support from Bristol-Myers Squibb/Sanofi and Cordis/Johnson & Johnson. He formerly served on a scientific advisory board for Bristol-Myers Squibb/Sanofi. He now serves on a scientific advisory board for Cordis/Johnson & Johnson and Genentech. He has spoken at scientific symposia supported by Merck and Co., Aventis, Bristol-Myers Squibb/Sanofi, and the Medicines Co.

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