Efficacy of ranolazine in patients with chronic angina observations from the randomized, double-blind, placebo-controlled MERLIN-TIMI (Metabolic Efficiency With Ranolazine for Less Ischemia in Non-ST-Segment Elevation Acute Coronary Syndromes) 36 Trial.

Abstract

OBJECTIVES:

We aimed to evaluate the efficacy and safety of ranolazine in a larger and more diverse group of patients with angina than previously studied.

BACKGROUND:

Ranolazine is an antianginal shown to reduce angina and improve exercise performance in selected patients with early-positive exercise testing and those with frequent angina.

METHODS:

We investigated the antianginal effects of ranolazine in the subgroup of patients with prior chronic angina (n = 3,565, 54%) enrolled in the randomized, double-blind, placebo-controlled MERLIN-TIMI (Metabolic Efficiency With Ranolazine for Less Ischemia in Non-ST Elevation Acute Coronary Syndromes) 36 trial of patients with acute coronary syndrome. Follow-up was a median of 350 days.

RESULTS:

Patients with prior angina received evidence-based therapy (95% aspirin, 78% statins, 89% beta-blockers, average 2.9 antianginal agents). The primary end point (cardiovascular death, myocardial infarction, recurrent ischemia) was less frequent with ranolazine (hazard ratio [HR]: 0.86; 95% confidence interval [CI]: 0.75 to 0.97; p = 0.017), due entirely to a significant reduction in recurrent ischemia (HR: 0.78; 95% CI: 0.67 to 0.91; p = 0.002). Ranolazine also reduced worsening angina (HR: 0.77; 95% CI: 0.59 to 1.00; p = 0.048) and intensification of antianginal therapy (HR: 0.77; 95% CI: 0.64 to 0.92, p = 0.005). Exercise duration at 8 months was greater with ranolazine (514 s vs. 482 s, p = 0.002). Cardiovascular death or myocardial infarction did not differ between treatment groups (HR: 0.97; 95% CI: 0.80 to 1.16; p = 0.71). Symptomatic documented arrhythmias (2.9% vs. 2.9%, p = 0.92) and total mortality (6.2% vs. 6.4%, p = 0.96) were similar with ranolazine or placebo.

CONCLUSIONS:

In this largest study of ranolazine in patients with established coronary artery disease, ranolazine was effective in reducing angina with favorable safety in a substantially broader group of patients with angina than previously studied. (Metabolic Efficiency With Ranolazine for Less Ischemia in Non-ST Elevation Acute Coronary Syndromes; NCT00099788).

• Authors: Sean R Wilson, Benjamin M Scirica, Eugene Braunwald, Sabina A Murphy, Ewa Karwatowska-Prokopczuk, Jacqueline L Buros, Bernard R Chaitman, David A Morrow
• Journal: Journal of the American College of Cardiology (J Am Coll Cardiol) Vol. 53 Issue 17 Pg. 1510-6 (Apr 28 2009) ISSN: 1558-3597 [Electronic] United States
• PMID: 19389561 (Publication Type: Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Acetanilides
• Enzyme Inhibitors
• Piperazines
• Ranolazine

Topics

• Acetanilides (adverse effects, therapeutic use)
• Acute Coronary Syndrome (drug therapy, mortality)
• Aged
• Angina Pectoris (drug therapy, mortality)
• Chronic Disease
• Cohort Studies
• Confidence Intervals
• Double-Blind Method
• Enzyme Inhibitors (adverse effects, therapeutic use)
• Exercise Test
• Exercise Tolerance
• Female
• Humans
• Kaplan-Meier Estimate
• Male
• Middle Aged
• Myocardial Ischemia (drug therapy, mortality)
• Piperazines (adverse effects, therapeutic use)
• Proportional Hazards Models
• Ranolazine