title: 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: OBJECTIVE
  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.affiliation: Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Sean R
authors.initials: SR
authors.lastname: Wilson
authors.forename: Benjamin M
authors.initials: BM
authors.lastname: Scirica
authors.forename: Eugene
authors.initials: E
authors.lastname: Braunwald
authors.forename: Sabina A
authors.initials: SA
authors.lastname: Murphy
authors.forename: Ewa
authors.initials: E
authors.lastname: Karwatowska-Prokopczuk
authors.forename: Jacqueline L
authors.initials: JL
authors.lastname: Buros
authors.forename: Bernard R
authors.initials: BR
authors.lastname: Chaitman
authors.forename: David A
authors.initials: DA
authors.lastname: Morrow
mesh_terms: D000083:Acetanilides / Q000009:adverse effects / Q000627:therapeutic use*; D054058:Acute Coronary Syndrome / Q000188:drug therapy* / Q000401:mortality; D000368:Aged; D000787:Angina Pectoris / Q000188:drug therapy* / Q000401:mortality; D002908:Chronic Disease; D015331:Cohort Studies; D016001:Confidence Intervals; D004311:Double-Blind Method; D004791:Enzyme Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D005080:Exercise Test; D017079:Exercise Tolerance; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D017202:Myocardial Ischemia / Q000188:drug therapy / Q000401:mortality; D010879:Piperazines / Q000009:adverse effects / Q000627:therapeutic use*; D016016:Proportional Hazards Models; D000069458:Ranolazine
chemical_list: D000083:Acetanilides; D004791:Enzyme Inhibitors; D010879:Piperazines; D000069458:Ranolazine