Ranolazine fails to meet primary endpoint in study, but reduces arrhythmias

March 27, 2007

Ranolazine, the latest antianginal medication approved in the United States, does not reduce the risk of cardiovascular events in patients with non-ST-elevation acute coronary syndromes (ACS) but may have a potential antiarrhythmic effect, said David A. Morrow, MD, MPH, at the American College of Cardiology's 56th annual scientific session.

Ranolazine, the latest antianginal medication approved in the United States, does not reduce the risk of cardiovascular events in patients with non-ST-elevation acute coronary syndromes (ACS) but may have a potential antiarrhythmic effect, said David A. Morrow, MD, MPH, at the American College of Cardiology's 56th annual scientific session.

In a trial known as MERLIN (Metabolic Efficiency with Ranolazine for Less Ischemia in Non-ST Elevation Acute Coronary Syndromes), 6,560 patients with non-ST-elevation ACS with clinical indicators of moderate to high risk of recurrent ischemic events were randomized to ranolazine. The drug was initiated intravenously followed by its oral extended-release formulation (1,000 mg/bid), or placebo for approximately 12 months in addition to standard medical therapy.

Patients in both groups were already well treated, with 96% on aspirin, 90% on an antithrombin, 90% on beta blockers, 82% on statins, 70% on ACE inhibitors or angiotensin receptor blockers, and 30% on oral nitrates.

The primary endpoint-a composite of cardiovascular 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 reductions in the incidence of recurrent ischemia (13% reduction; p = 0.03), worsening angina (23% reduction; p = 0.023), and the need for antianginal therapy (19% reduction; p =0.006), compared with placebo.

The risk of clinically significant arrhythmias on Holter monitoring was reduced by a significant 11% (p

The safety of ranolazine had been uncertain because it was associated with slight prolongation of the QT interval although experimental data had suggested that it suppressed of pro-arrhythmic markers, said Dr. Morrow, who is in the cardiovascular division at Brigham and Women's Hospital, Boston.

The new data from MERLIN offers reassurance that ranolazine is safe for long-term administration and may even be anti-arrhythmic, he said.

"The significant reduction in recurrent ischemia provides evidence for efficacy as an antianginal agent in a broader population ever studied before with ranolazine," he said.