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

J Am Coll Cardiol. 2009 Apr 28;53(17):1510-6. doi: 10.1016/j.jacc.2009.01.037.

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).

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

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

Substances

  • Acetanilides
  • Enzyme Inhibitors
  • Piperazines
  • Ranolazine

Associated data

  • ClinicalTrials.gov/NCT00099788