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Effect of ranolazine on atrial fibrillation in patients with non-ST elevation acute coronary syndromes: observations from the MERLIN-TIMI 36 trial.

AbstractAIMS:
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.
METHODS AND 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).
CONCLUSION:
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.
CLINICAL TRIAL REGISTRATION:
NCT00099788.
AuthorsBenjamin M Scirica, Luiz Belardinelli, Bernard R Chaitman, Jonathan W Waks, Samuel Volo, Ewa Karwatowska-Prokopczuk, Sabina A Murphy, Mei L Cheng, Eugene Braunwald, David A Morrow
JournalEuropace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology (Europace) Vol. 17 Issue 1 Pg. 32-7 (Jan 2015) ISSN: 1532-2092 [Electronic] England
PMID25210025 (Publication Type: Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
CopyrightPublished on behalf of the European Society of Cardiology. All rights reserved. © The Author 2014. For permissions please email: [email protected].
Chemical References
  • Acetanilides
  • Piperazines
  • Sodium Channel Blockers
  • Ranolazine
Topics
  • Acetanilides (administration & dosage)
  • Acute Coronary Syndrome (drug therapy, mortality)
  • Age Distribution
  • Aged
  • Aged, 80 and over
  • Atrial Fibrillation (drug therapy, mortality, prevention & control)
  • Comorbidity
  • Drug Administration Schedule
  • Female
  • Humans
  • Longitudinal Studies
  • Male
  • Massachusetts (epidemiology)
  • Piperazines (administration & dosage)
  • Placebo Effect
  • Prevalence
  • Ranolazine
  • Risk Factors
  • Sodium Channel Blockers (administration & dosage)
  • Survival Rate
  • Treatment Outcome

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