MERLIN TIMI-36 Trial shows ranolazine reduces ventricular and atrial arrhythmias in patients with acute non-ST elevation infarctions
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.
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