Metabolic Efficiency With Ranolazine for Less Ischemia in NSTE-ACS - MERLIN-TIMI 36


The goal of the trial was to evaluate the safety and efficacy of long-term treatment with ranolazine compared with placebo among patients with non-ST elevation acute coronary syndrome (NSTE-ACS).

Study Design

Patients Enrolled: 6,560
Mean Follow Up: Median, 348 days
Mean Patient Age: Median age, 64 years
Female: 35

Patient Populations:

Hospitalized with NSTE-ACS; ischemic symptoms at rest within 48 hours; and at least one indicator of moderate to high risk, defined as elevated troponin or creatine kinase-myocardial band, ST-depression ≥0.1 mV, diabetes, or TIMI risk score for unstable angina/NSTEMI ≥3


Successful revascularization of culprit vessel prior to randomization, pulmonary edema requiring intubation, sustained systolic blood pressure <90 mm Hg or shock, or clinically significant hepatic disease or end-stage renal disease

Primary Endpoints:

Composite of CV death, MI, or recurrent ischemia

Secondary Endpoints:

Composites of CV death, MI, severe recurrent ischemia; composites of CV death, MI, severe recurrent ischemia, and positive Holter at 30 days

Drug/Procedures Used:

Patients were randomized in a double-blind manner to ranolazine (n = 3,279) or matching placebo (n = 3,281). Study drug was administered as 200 mg intravenously for 1 hour, followed by an 80 mg/h intravenous infusion and then a long-term oral phase with ranolazine or placebo given 1000 mg twice daily for the duration of the trial (median 348 days). Continuous Holter monitoring was performed for the first week of the trial.

Principal Findings:

Non-ST elevation myocardial infarction (MI) was the presenting syndrome in 51% of patients. Median time from symptom onset to randomization was 24 hours. One-third of patients had a history of diabetes and one-third had prior MI. Coronary angiography was performed in 59% of patients during the index hospitalization.

The primary endpoint of cardiovascular (CV) death, MI, or recurrent ischemia occurred in 21.8% of the ranolazine group and 23.5% of the placebo group (hazard ratio [HR] 0.92, 95% confidence interval 0.83-1.02, p = 0.11). Among the components of the composite, there was no difference in CV death or MI (10.4% vs. 10.5%, HR 0.99, p = 0.87), but recurrent ischemia was significantly lower in the ranolazine group (17.3% vs. 20.0%, HR 0.87, p = 0.030). CV death, MI, severe recurrent ischemia, or positive Holter at 30 days occurred in 23.1% of the ranolazine group and 25.1% of the placebo group (p = 0.055). The need for increase in antianginal therapy was lower in the ranolazine group (10% vs. 12.2%, p = 0.006), as was worsening angina (4.2% vs. 5.9%, p = 0.023).

All-cause mortality did not differ between groups (HR 0.99, p = 0.91), nor did the composite of death or CV hospitalization (HR 0.98, p = 0.67). Symptomatic documented arrhythmia occurred in 99 patients in the ranolazine group and 102 in the placebo group (p = 0.84). Clinically significant arrhythmia on Holter occurred less frequently in the ranolazine group (73.7% vs. 83.1%, p < 0.001). Syncope as an adverse event was reported in 3% of the ranolazine group and 2% of the placebo group (p = 0.01).


Among patients with NSTE-ACS, treatment with ranolazine was not associated with a difference in the primary composite endpoint of CV death, MI, or recurrent ischemia through a median 1-year follow-up compared with placebo.

Ranolazine has previously been studied as an antianginal agent in patients with chronic angina. The present study was conducted not in chronic angina patients, but in patients with NSTE-ACS. There was no difference in death or MI, but there were improvements in recurrent ischemia and the need for anginal therapy intensification with ranolazine, a not surprising finding given its indication as an antianginal agent. Among the safety endpoints, mortality did not differ between the treatment groups, and there was no difference in symptomatic documented arrhythmia. During the Holter monitoring in the first week, fewer patients on ranolazine had clinically significant arrhythmia.


Morrow DA, Scirica BM, Karwatowska-Prokopczuk E, et al. Effects of Ranolazine on Recurrent Cardiovascular Events in Patients With Non-ST-Elevation Acute Coronary Syndromes: The MERLIN-TIMI 36 Randomized Trial. JAMA 2007;297:1775-83.

Presented by Dr. David Morrow at the American College of Cardiology Annual Scientific Session, New Orleans, LA, March 2007.

Clinical Topics: Acute Coronary Syndromes, Arrhythmias and Clinical EP, Invasive Cardiovascular Angiography and Intervention, Noninvasive Imaging, SCD/Ventricular Arrhythmias, Atrial Fibrillation/Supraventricular Arrhythmias, Interventions and ACS, Interventions and Imaging, Angiography, Nuclear Imaging

Keywords: Myocardial Infarction, Acute Coronary Syndrome, Follow-Up Studies, Creatine Kinase, MB Form, Syncope, Enzyme Inhibitors, Piperazines, Coronary Angiography, Electrocardiography, Ambulatory, Confidence Intervals, Infusions, Intravenous, Diabetes Mellitus, Troponin

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