title: Effect of ranolazine on atrial fibrillation in patients with non-ST elevation acute coronary syndromes: observations from the MERLIN-TIMI 36 trial.
abstract: OBJECTIVE
  To determine the effect of ranolazine, an anti-ischaemic agent with anti-arrhythmic properties, on the overall burden of atrial fibrillation (AF) in acute coronary syndromes (ACS) and determine whether ranolazine reduces the long-term incidence of clinical AF after ACS.
  
  
  RESULTS
  MERLIN-TIMI 36 randomized patients with non-ST elevation ACS to ranolazine or placebo. Atrial fibrillation episodes detected on continuous electrocardiogram (cECG) monitoring were reviewed in 6351 patients (97% of trial). Atrial fibrillation burden was categorized according to the time in AF: clinically insignificant AF (<0.01% of time), paroxysmal AF (>0.01-98%), or predominantly persistent AF (>98%). Clinical AF events were identified through adverse event reporting for a median 1-year follow-up. Overall, patients assigned to ranolazine had a trend towards fewer episodes of AF [75 (2.4%) vs. 55 (1.7%) patients, P = 0.08] detected on cECG during the first 7 days after randomization. The pattern of new-onset AF differed between ranolazine vs. placebo: clinically insignificant AF (five patients in ranolazine vs. seven in placebo), paroxysmal AF (18 vs. 48 patients), and predominantly chronic AF (28 vs. 20 patients, three-way P < 0.01). Among patients with a paroxysmal AF pattern, the overall burden was lower with ranolazine than with placebo (median 4.4 vs.16.1%, P = 0.015). Over the median 1-year follow-up, fewer patients treated with ranolazine experienced an AF event compared with placebo (2.9 vs. 4.1%, RR 0.71, P = 0.01).
  
  
  CONCLUSIONS
  Ranolazine, an anti-anginal agent with electrophysiological effects, may reduce the frequency of paroxysmal AF in patients with non-ST elevation ACS with a pattern of lower overall AF burden in this group. Ranolazine reduced the overall 1-year incidence of clinical AF events. These atrial-specific anti-arrhythmic properties of ranolazine may be of clinical interest and warrant additional investigation.
  
  
  BACKGROUND
  NCT00099788.
authors.affiliation: TIMI Study Group, Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital, and Harvard Medical School, 75 Francis Street, Boston, MA 02115, USA bscirica@partners.org.
authors.forename: Benjamin M
authors.initials: BM
authors.lastname: Scirica
authors.affiliation: Gilead Science, Inc., Foster City, CA, USA.
authors.forename: Luiz
authors.initials: L
authors.lastname: Belardinelli
authors.affiliation: St. Louis University School of Medicine, St. Louis, MO, USA.
authors.forename: Bernard R
authors.initials: BR
authors.lastname: Chaitman
authors.affiliation: TIMI Study Group, Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital, and Harvard Medical School, 75 Francis Street, Boston, MA 02115, USA.
authors.forename: Jonathan W
authors.initials: JW
authors.lastname: Waks
authors.affiliation: TIMI Study Group, Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital, and Harvard Medical School, 75 Francis Street, Boston, MA 02115, USA.
authors.forename: Samuel
authors.initials: S
authors.lastname: Volo
authors.affiliation: Gilead Science, Inc., Foster City, CA, USA.
authors.forename: Ewa
authors.initials: E
authors.lastname: Karwatowska-Prokopczuk
authors.affiliation: TIMI Study Group, Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital, and Harvard Medical School, 75 Francis Street, Boston, MA 02115, USA.
authors.forename: Sabina A
authors.initials: SA
authors.lastname: Murphy
authors.affiliation: Gilead Science, Inc., Foster City, CA, USA.
authors.forename: Mei L
authors.initials: ML
authors.lastname: Cheng
authors.affiliation: TIMI Study Group, Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital, and Harvard Medical School, 75 Francis Street, Boston, MA 02115, USA.
authors.forename: Eugene
authors.initials: E
authors.lastname: Braunwald
authors.affiliation: TIMI Study Group, Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital, and Harvard Medical School, 75 Francis Street, Boston, MA 02115, USA.
authors.forename: David A
authors.initials: DA
authors.lastname: Morrow
mesh_terms: D000083:Acetanilides / Q000008:administration & dosage*; D054058:Acute Coronary Syndrome / Q000188:drug therapy* / Q000401:mortality*; D017677:Age Distribution; D000368:Aged; D000369:Aged, 80 and over; D001281:Atrial Fibrillation / Q000188:drug therapy / Q000401:mortality* / Q000517:prevention & control*; D015897:Comorbidity; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008404:Massachusetts / Q000453:epidemiology; D010879:Piperazines / Q000008:administration & dosage*; D015990:Placebo Effect; D015995:Prevalence; D000069458:Ranolazine; D012307:Risk Factors; D026941:Sodium Channel Blockers / Q000008:administration & dosage; D015996:Survival Rate; D016896:Treatment Outcome
chemical_list: D000083:Acetanilides; D010879:Piperazines; D026941:Sodium Channel Blockers; D000069458:Ranolazine
keywords: Acute coronary syndromes; Anti-arrhythmic therapy; Atrial fibrillation; Ranolazine