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Ranolazine to Treat Acute Coronary Syndromes?

In a large, randomized trial, adding ranolazine to standard ACS treatment produced no reduction in major adverse cardiac events.

In several studies, ranolazine has reduced symptoms and increased time to angina or ST-segment depression during exercise in patients with chronic angina (Journal Watch Cardiology Apr 2 2004). Might ranolazine have a role in treating non–ST-elevation acute coronary syndromes (ACS)? To find out, investigators in the manufacturer-funded MERLIN-TIMI 36 study randomized 6560 patients (mean age, 64) with ACS symptoms to either ranolazine (intravenous for 12 to 96 hours, then 1000 mg oral twice daily) or placebo. All patients also received standard therapy: medical management in 60.5%, percutaneous intervention in 31.6%, and coronary artery bypass surgery in 7.9%. Median follow-up was 348 days.

The ranolazine and placebo groups showed no significant differences in the primary endpoint, a composite of cardiovascular death, MI, or recurrent ischemia (21.8% vs. 23.5%, respectively) or in the secondary endpoints of CV death, MI, or severe recurrent ischemia. The cumulative incidence of recurrent ischemia was slightly lower in the ranolazine than in the placebo group (13.9% vs. 16.1%); this difference was driven by reductions in the rate of worsening angina and in the need to titrate antianginal therapy, particularly in women and in patients with prior angina. Incidences of syncope and QTc prolongation were significantly higher in the ranolazine group than in the placebo group (3.3% vs. 2.3% and 0.9% vs. 0.3%, respectively).

Comment: In this large, randomized trial, ranolazine did not improve the prognosis of patients with ACS. Although the observed reduction in recurrent ischemia warrants further investigation, so do the increased risks for syncope and QTc prolongation. As editorialists note, until results of such studies are available, guideline-recommended beta-blockers and nitrates should remain first-line therapies for ACS, and ranolazine should be reserved for second-line treatment in patients with recurrent angina.

— Joanne M. Foody, MD

Published in Journal Watch Cardiology April 25, 2007

Citation(s):

Morrow DA et al. Effects of ranolazine on recurrent cardiovascular events in patients with non–ST-elevation acute coronary syndromes: The MERLIN-TIMI 36 randomized trial. JAMA 2007 Apr 25; 297:1775-83.

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• Medline abstract (Free)

Newby LK and Peterson ED. Does ranolazine have a place in the treatment of acute coronary syndromes? JAMA 2007 Apr 25; 297:1823-5.

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• Medline abstract (Free)