MERLIN-TIMI 36: Metabolic Efficiency With Ranolazine for Less Ischemia in Non-ST Elevation Acute Coronary Syndromes

Luis Gruberg, MD, FACC


April 30, 2007

In This Article


The MERLIN-TIMI 36 trial shows that the use of ranolazine can be extended to a broader population of patients than previously studied who present with an acute coronary syndrome.

Presenter: David A. Morrow, MD, MPH (Brigham and Women's Hospital, Boston, Massachusetts) on Behalf of the MERLIN-TIMI 36 Investigators

Ranolazine is an oral antianginal and anti-ischemic drug indicated for the treatment of chronic angina in patients who fail to respond to conventional treatment. Ranolazine has a novel mechanism of action; it inhibits the late INa channels diminishing calcium overload without a clinically significant effect on heart rate or blood pressure. Previous studies have shown that ranolazine is associated with a prolongation of the QTC (average, 5 seconds) -- a finding that has limited its use as a second-line therapy in patients who continue to experience angina despite treatment with other antianginal agents.

The Metabolic Efficiency with Ranolazine for Less Ischemia in Non-ST Elevation Acute Coronary Syndromes (MERLIN)-TIMI 36 trial assessed the acute and chronic efficacy and the safety of ranolazine in patients with unstable angina/non-ST-elevation myocardial infarction (UA/NSTEMI) who were receiving conventional therapy.

Study Design

MERLIN-TIMI 36 was a double-blind, parallel-group, placebo-controlled trial that randomized patients with UA/NSTEMI in a 1:1 double-blind fashion to either ranolazine or matched placebo. Treatment was initiated as intravenous 200 mg over 1 hour, followed by 80-mg/hour infusion up to 96 hours. Thereafter, patients were treated with either oral ranolazine 1000 mg twice daily or placebo for the duration of the study.

All patients underwent Holter monitoring and were followed for 348 days. Patients needed at least 1 indicator of moderate-to-high risk (enzymes, ST depression, diabetes, or TIMI score ≥ 3). Patients needed to be enrolled prior to revascularization (if planned).

Primary endpoint: Composite of cardiovascular death, new or recurrent MI, and recurrent ischemia.

Secondary endpoints:

  • Cardiovascular death, MI, and severe recurrent ischemia; and

  • Cardiovascular death, MI, severe recurrent ischemia, and positive Holter monitoring.


Between October 2004 and May 2006, 6560 patients were randomized to placebo (n = 3281) or ranolazine (n = 3279). Baseline clinical characteristics, including concomitant medical therapy, were well balanced between the 2 groups (Table 1).

At a mean 540 days follow-up, the rate of the primary endpoint (composite endpoint of cardiovascular death, new or recurrent MI, and recurrent ischemia) trended lower in the ranolazine group, but the difference was not statistically significant (23.5% vs 21.8%, respectively; P = .11). When the individual components of the primary endpoint were analyzed separately, there was a significantly lower incidence of recurrent ischemia in patients randomized to ranolazine (Table 2). Worsening of angina was also significantly reduced in these patients (5.9% vs 4.2%, P = .02). There was no difference in the incidence of cardiac death or MI or in the rate of sudden cardiac death. However, there was a significantly lower rate of clinically significant arrhythmia in patients randomized to ranolazine (Table 2).


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