title: The risk of sudden cardiac death in patients with non-ST elevation acute coronary syndrome and prolonged QTc interval: effect of ranolazine.
abstract: OBJECTIVE
  Clinical utility of QTc prolongation as a predictor for sudden cardiac death (SCD) has not been definitely established. Ranolazine causes modest QTc prolongation, yet it shows antiarrhythmic properties. We aimed to determine the association between prolonged QTc and risk of SCD, and the effect of ranolazine on this relationship.
  
  
  RESULTS
  The relationship between baseline QTc and SCD was studied in 6492 patients with non-ST elevation acute coronary syndrome (NSTEACS) randomized to placebo or ranolazine in the MERLIN-TIMI 36 trial. In the placebo group, an abnormal QTc interval (≥450 ms in men, ≥470 ms in women) was associated with a two-fold increased risk of SCD (hazard ratio, HR, 2.3, P = 0.005) after adjustment for other risk factors (age ≥75 years, NYHA class III/IV, high TIMI risk score, ventricular tachycardia ≥8 beats, digitalis, and antiarrhythmics). In the ranolazine group, the association between abnormal QTc and SCD was similar to placebo, but not significant (HR 1.8, P = 0.074). There was no significant difference between placebo and ranolazine in the risk for SCD in patients with abnormal QTc (HR 0.78, P = 0.48). When QTc was used as a continuous variable, for every 10 ms increase in QTc, hazard rate for SCD increased significantly by 8% (P = 0.007) in the placebo group, and only by 2.9% (P = 0.412; P for interaction=0.25) in the ranolazine group.
  
  
  CONCLUSIONS
  In NSTEACS patients treated with placebo, prolonged QTc was a significant independent predictor for SCD. Ranolazine, compared with placebo, was not associated with increased risk for SCD in patients with prolonged QTc.
authors.affiliation: Gilead Sciences, Inc, 333 Lakeside Drive, Foster City, CA 94404, USA. ewa.prokopczuk@gilead.com
authors.forename: Ewa
authors.initials: E
authors.lastname: Karwatowska-Prokopczuk
authors.forename: Whedy
authors.initials: W
authors.lastname: Wang
authors.forename: Mei L
authors.initials: ML
authors.lastname: Cheng
authors.forename: Dewan
authors.initials: D
authors.lastname: Zeng
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Schwartz
authors.forename: Luiz
authors.initials: L
authors.lastname: Belardinelli
mesh_terms: D000083:Acetanilides / Q000009:adverse effects / Q000627:therapeutic use*; D054058:Acute Coronary Syndrome / Q000150:complications / Q000175:diagnosis / Q000188:drug therapy* / Q000503:physiopathology; D000368:Aged; D002317:Cardiovascular Agents / Q000009:adverse effects / Q000627:therapeutic use*; D016757:Death, Sudden, Cardiac / Q000209:etiology*; D004562:Electrocardiography; D005260:Female; D006801:Humans; D015994:Incidence; D053208:Kaplan-Meier Estimate; D008133:Long QT Syndrome / Q000139:chemically induced / Q000175:diagnosis / Q000209:etiology* / Q000503:physiopathology; D008297:Male; D015999:Multivariate Analysis; D010879:Piperazines / Q000009:adverse effects / Q000627:therapeutic use*; D016016:Proportional Hazards Models; D016032:Randomized Controlled Trials as Topic; D000069458:Ranolazine; D012189:Retrospective Studies; D018570:Risk Assessment; D012307:Risk Factors; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D000083:Acetanilides; D002317:Cardiovascular Agents; D010879:Piperazines; D000069458:Ranolazine