Document Detail

Effect of ranolazine, an antianginal agent with novel electrophysiological properties, on the incidence of arrhythmias in patients with non ST-segment elevation acute coronary syndrome: results from the Metabolic Efficiency With Ranolazine for Less Ischemia in Non ST-Elevation Acute Coronary Syndrome Thrombolysis in Myocardial Infarction 36 (MERLIN-TIMI 36) randomized controlled trial.
MedLine Citation:
PMID:  17804441     Owner:  NLM     Status:  MEDLINE    
BACKGROUND: Ranolazine, a piperazine derivative, reduces ischemia via inhibition of the late phase of the inward sodium current (late I(Na)) during cardiac repolarization, with a consequent reduction in intracellular sodium and calcium overload. Increased intracellular calcium leads to both mechanical dysfunction and electric instability. Ranolazine reduces proarrhythmic substrate and triggers such as early afterdepolarization in experimental models. However, the potential antiarrhythmic actions of ranolazine have yet to be demonstrated in humans. METHODS AND RESULTS: The Metabolic Efficiency With Ranolazine for Less Ischemia in Non-ST-Elevation Acute Coronary Syndrome (MERLIN)-Thrombolysis in Myocardial Infarction (TIMI) 36 (MERLIN-TIMI 36) trial randomized 6560 patients hospitalized with a non-ST-elevation acute coronary syndrome to ranolazine or placebo in addition to standard therapy. Continuous ECG (Holter) recording was performed for the first 7 days after randomization. A prespecified set of arrhythmias were evaluated by a core laboratory blinded to treatment and outcomes. Of the 6560 patients in MERLIN-TIMI 36, 6351 (97%) had continuous ECG recordings that could be evaluated for arrhythmia analysis. Treatment with ranolazine resulted in significantly lower incidences of arrhythmias. Specifically, fewer patients had an episode of ventricular tachycardia lasting > or = 8 beats (166 [5.3%] versus 265 [8.3%]; P<0.001), supraventricular tachycardia (1413 [44.7%] versus 1752 [55.0%]; P<0.001), or new-onset atrial fibrillation (55 [1.7%] versus 75 [2.4%]; P=0.08). In addition, pauses > or = 3 seconds were less frequent with ranolazine (97 [3.1%] versus 136 [4.3%]; P=0.01). CONCLUSIONS: Ranolazine, an inhibitor of late I(Na), appears to have antiarrhythmic effects as assessed by continuous ECG monitoring of patients in the first week after admission for acute coronary syndrome. Studies specifically designed to evaluate the potential role of ranolazine as an antiarrhythmic agent are warranted.
Benjamin M Scirica; David A Morrow; Hanoch Hod; Sabina A Murphy; Luiz Belardinelli; Chester M Hedgepeth; Peter Molhoek; Freek W A Verheugt; Bernard J Gersh; Carolyn H McCabe; Eugene Braunwald
Publication Detail:
Type:  Journal Article; Randomized Controlled Trial; Research Support, Non-U.S. Gov't     Date:  2007-09-05
Journal Detail:
Title:  Circulation     Volume:  116     ISSN:  1524-4539     ISO Abbreviation:  Circulation     Publication Date:  2007 Oct 
Date Detail:
Created Date:  2007-10-09     Completed Date:  2007-11-13     Revised Date:  2007-11-15    
Medline Journal Info:
Nlm Unique ID:  0147763     Medline TA:  Circulation     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1647-52     Citation Subset:  AIM; IM    
TIMI Study Group, Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital, and Harvard Medical School, 75 Francis St, Boston, MA 02115, USA.
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MeSH Terms
Acetanilides / adverse effects*,  therapeutic use*
Acute Disease
Angina Pectoris / drug therapy,  physiopathology*,  prevention & control*
Arrhythmias, Cardiac / chemically induced,  epidemiology*
Coronary Disease / complications,  drug therapy*
Diabetic Angiopathies / epidemiology
Middle Aged
Myocardial Infarction / complications,  physiopathology*
Myocardial Ischemia / drug therapy*
Piperazines / adverse effects*,  therapeutic use*
Tachycardia / epidemiology
Thrombolytic Therapy
Reg. No./Substance:
0/Acetanilides; 0/Piperazines; 0/Placebos; 110445-25-5/ranolazine

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