Ranolazine Safe for Long-Term Use, May Reduce Arrhythmias

Internal Medicine World Report, September 2007, Volume 0, Issue 0

Does Not Lower CV Events in Patients with ACS

By Wayne Kuznar

NEW ORLEANS—The latest antianginal agent approved in the United States, ranolazine (Ranexa), does not reduce the risk of cardiovascular (CV) events in patients with non?ST-elevation acute coronary syndromes (ACS), but it is safe for long-term administration and may have antiarrhythmic effects, said David A. Morrow, MD, MPH, at the American College of Cardiology annual meeting.

The long-term safety of ranolazine had been uncertain, because it was associated with a slight prolongation of the QT interval. For this reason, it was approved in 2006 as second-line therapy in patients who continue to experience angina despite treatment with other antianginal medications.

"However, experimental data suggest suppression of proarrhythmic markers [with ranolazine]," said Dr Morrow, associate physician in the Division of Cardiovascular Medicine at Brigham and Women's Hospital, Boston.

David A. Morrow,MD,MPH

Dr Morrow presented data from the Metabolic Efficiency with Ranolazine for Less Ischemia in Non?ST-Elevation Acute Coronary Syndromes (MERLIN) trial. In MERLIN, 6560 patients with non?ST-elevation ACS and clinical indicators of a moderate-to-high risk for recurrent ischemic events were randomized to ranolazine or placebo for approximately 12 months in addition to standard medical therapy. IV ranolazine was administered for upto 96 hours, followed by its oral extended-release formulation (1000 mg twice daily).

The 3 main study goals were: ranolazine's impact on acute efficacy (effect on major coronary events), chronic efficacy (effect on major coronary events and recurrent ischemia), and patient safety.

Patients in both groups were already well treated, with 96% taking aspirin, 90% taking an antithrombin, 90% taking beta-blockers, 82% taking statins, 79% taking angiotensin-converting-enzyme inhibitors or angiotensin receptor blockers, and 30% taking an oral nitrate agent.

The primary end point—a composite of CV death, myocardial infarction, or recurrent ischemia—occurred in 21.8% of patients randomized to ranolazine and 23.5% randomized to placebo, a nonsignificant difference.

In the patients randomized to ranolazine, however, there were significant differences in the incidence of recurrent ischemia (13% reduction), worsening angina (23% reduction), and need for antianginal therapy (19% reduction), compared with placebo. Events during follow-up are listed in the Table.

Table. Events during follow-up: ranolazine vs placebo







CV death, MI, or recurrent

ischemia (primary end point)




CV death or MI




Recurrent ischemia




MI = myocardial infarction.

The risk of clinically significant arrhythmias on Holter monitoring was reduced by a significant 11% in the patients assigned to ranolazine.

These new data offer reassurance that ranolazine is safe for long-term use and may even be antiarrhythmic, said Dr Morrow. "The significant reduction in recurrent ischemia provides evidence for efficacy as an antianginal agent in a broader population [than] ever studied before with ranolazine," he said. "The significant antiarrhythmic effects of ranolazine suggested by a significant reduction in arrhythmias warrant additional investigation."

The results from MERLIN maybe the basis for approval of ranolazine as a first-line treatment for angina,he added.