心室性不整脈の軽減

MERLIN TIMI-36 data show that extended-release ranolazine reduces ventricular and atrial arrhythmias in patients with acute non-ST elevation myocardial infarctions or unstable angina who are already receiving standard therapy, according to a presentation at the annual meeting of the European Society of Cardiology.

MERLIN TIMI-36 (Metabolic Efficiency with Ranolazine for Less Ischemia in Non-ST Elevation Acute Coronary Syndromes) was a multi-national, double-blind, randomized, placebo-controlled, parallel-group clinical trial designed to evaluate the efficacy and safety of the extended-release drug formulation during acute and long-term treatment in 6,560 patients (3,279 received ranolazine, 3,281 received placebo) with non-ST elevation acute coronary syndrome treated with standard therapy.

Within 48 hours of onset of angina, eligible hospitalized patients were enrolled in the study and randomized to intravenous drug or placebo, followed by long-term outpatient treatment with extended-release drug or placebo. All patients also received standard therapy during both hospital-based and outpatient treatment. The doses of ranolazine extended-release tablets used in MERLIN TIMI-36 have been studied in previous Phase III clinical trials.

Participants in the MERLIN TIMI-36 study received modern therapy, with approximately 96 percent of patients on aspirin, approximately 89 percent on beta blockers and approximately 82 percent on statins. Approximately 59 percent of study participants received coronary angiography during their initial hospitalization.

The ranolazine group had a 37-percent reduction in relative risk of ventricular tachycardia lasting eight beats or more and fewer episodes of sudden cardiac death (56 deaths) compared with placebo patients (65 deaths).

As part of the MERLIN TIMI-36 safety assessment, Holter monitors recorded continuous electrocardiographic (ECG) recordings for the first seven days after patients were admitted to the study with an episode of non-ST elevation myocardial infarction or unstable angina. The more than 1,000,000 hours of Holter monitor data from 6,351 study participants are believed to represent the largest Holter monitor database ever collected in a clinical trial.

"The significant reductions in ventricular arrhythmias observed in ranolazine patients in the MERLIN TIMI-36 study provide important and reassuring data regarding the long-term safety of ranolazine and suggest that ranolazine could have potential as a new anti-arrhythmic agent in treating ventricular arrhythmias," said Benjamin Scirica, a cardiologist at Brigham and Women's hospital, an investigator at the TIMI Study group and lead author of the study.

These data represent the first clinical report of the effect of ranolazine to reduce the incidence of cardiac arrhythmias and support the findings of many prior preclinical studies that suggested ranolazine has potential anti-arrhythmic properties due to its action as an inhibitor of the late sodium current.

Extended release ranolazine is currently indicated in the USA for treatment of chronic angina in patients who have not achieved an adequate response with other antianginal drugs, and should be used in combination with amlodipine, beta-blockers or nitrates.