Advertisement

Comparison of Effectiveness of Ranolazine Plus Amiodarone Versus Amiodarone Alone for Conversion of Recent-Onset Atrial Fibrillation

      Ranolazine, an antianginal agent with antiarrhythmic properties, prevents atrial fibrillation (AF) in patients with acute coronary syndrome. In experimental models, the combination of ranolazine and amiodarone has marked synergistic effects that potently suppress AF. Currently, the clinical effect of the ranolazine–amiodarone combination for the conversion of AF is unknown. This prospective randomized pilot study compared the safety and efficacy of ranolazine plus amiodarone versus amiodarone alone for the conversion of recent-onset AF. We enrolled 51 consecutive patients with AF (<48-hour duration) eligible for pharmacologic cardioversion. Patients (33 men, 63 ± 8 years of age) were randomized to intravenous amiodarone for 24 hours (group A, n = 26) or to intravenous amiodarone plus oral ranolazine 1,500 mg at time of randomization (group A + R, n = 25). The 2 groups were well balanced with respect to clinical characteristics and left atrial diameter. Conversion within 24 hours (primary end point) was achieved in 22 patients (88%) in group A + R versus 17 patients (65%) in group A (p = 0.056). Time to conversion was shorter in group A + R than in group A (9.8 ± 4.1 vs 14.6 ± 5.3 hours, p = 0.002). According to Cox regression analysis, left atrial diameter and A + R treatment were the only independent predictors of time to conversion (hazard ratio 5.35, 95% confidence interval 2.37 to 12.11, p <0.001; hazard ratio 0.81, 95% confidence interval 0.74 to 0.88, p <0.001, respectively). There were no proarrhythmic events in either group. In conclusion, addition of ranolazine to standard amiodarone therapy is equally safe and appears to be more effective compared to amiodarone alone for conversion of recent-onset AF.
      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribe:

      Subscribe to American Journal of Cardiology
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Camm A.J.
        • Kirchhof P.
        • Lip G.Y.
        • Schotten U.
        • Savelieva I.
        • Ernst S.
        • Van Gelder I.C.
        • Al-Attar N.
        • Hindricks G.
        • Prendergast B.
        • Heidbuchel H.
        • Alfieri O.
        • Angelini A.
        • Atar D.
        • Colonna P.
        • De Caterina R.
        • De Sutter J.
        • Goette A.
        • Gorenek B.
        • Heldal M.
        • Hohloser S.H.
        • Kolh P.
        • Le Heuzey J.Y.
        • Ponikowski P.
        • Rutten F.H.
        Guidelines for the management of atrial fibrillation: the Task Force for the Management of Atrial Fibrillation of the European Society of Cardiology (ESC).
        Eur Heart J. 2010; 31: 2369-2429
        • Savelieva I.
        • Camm J.
        Anti-arrhythmic drug therapy for atrial fibrillation: current anti-arrhythmic drugs, investigational agents, and innovative approaches.
        Europace. 2008; 10: 647-655
        • Kochiadakis G.E.
        • Igoumenidis N.E.
        • Hamilos M.E.
        • Marketou M.E.
        • Chlouverakis G.I.
        • Vardas P.E.
        A comparative study of the efficacy and safety of procainamide versus propafenone versus amiodarone for the conversion of recent-onset atrial fibrillation.
        Am J Cardiol. 2007; 99: 1721-1725
        • Vardas P.E.
        • Kochiadakis G.E.
        • Igoumenidis N.E.
        • Tsatsakis A.M.
        • Simantirakis E.N.
        • Chlouverakis G.I.
        Amiodarone as a first-choice drug for restoring sinus rhythm in patients with atrial fibrillation: a randomized, controlled study.
        Chest. 2000; 117: 1538-1545
        • Antzelevitch C.
        • Belardinelli L.
        • Zygmunt A.C.
        • Burashnikov A.
        • Di Diego J.M.
        • Fish J.M.
        • Cordeiro J.M.
        • Thomas G.
        Electrophysiological effects of ranolazine, a novel antianginal agent with antiarrhythmic properties.
        Circulation. 2004; 110: 904-910
        • Stone P.H.
        Ranolazine: new paradigm for management of myocardial ischemia, myocardial dysfunction, and arrhythmias.
        Cardiol Clin. 2008; 26: 603-614
        • Scirica B.M.
        • Morrow D.A.
        • Hod H.
        • Murphy S.A.
        • Belardinelli L.
        • Hedgepeth C.M.
        • Molhoek P.
        • Verheugt F.W.
        • Gersh B.J.
        • McCabe C.H.
        • Braunwald E.
        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.
        Circulation. 2007; 116: 1647-1652
        • Miles R.H.
        • Passman R.
        • Murdock D.K.
        Comparison of effectiveness and safety of ranolazine versus amiodarone for preventing atrial fibrillation after coronary artery bypass grafting.
        Am J Cardiol. 2011; 108: 673-676
        • Sicouri S.
        • Burashnikov A.
        • Belardinelli L.
        • Antzelevitch C.
        Synergistic electrophysiologic and antiarrhythmic effects of the combination of ranolazine and chronic amiodarone in canine atria.
        Circ Arrhythm Electrophysiol. 2010; 3: 88-95
        • Burashnikov A.
        • Sicouri S.
        • Di Diego J.M.
        • Belardinelli L.
        • Antzelevitch C.
        Synergistic effect of the combination of ranolazine and dronedarone to suppress atrial fibrillation.
        J Am Coll Cardiol. 2010; 56: 1216-1224
        • Chevalier P.
        • Durand-Dubief A.
        • Burri H.
        • Cucherat M.
        • Kirkorian G.
        • Touboul P.
        Amiodarone versus placebo and class ic drugs for cardioversion of recent-onset atrial fibrillation: a meta-analysis.
        J Am Coll Cardiol. 2003; 41: 255-262
        • Ranexa prescribing information
        (Accessed April 23, 2012)
        • Mitchell L.B.
        • Wyse D.G.
        • Gillis A.M.
        • Duff H.J.
        Electropharmacology of amiodarone therapy initiation.
        Circulation. 1989; 80: 34-42
        • Kowey P.R.
        • Marinchak R.A.
        • Rials S.J.
        • Filart R.A.
        Acute treatment of atrial fibrillation.
        Am J Cardiol. 1998; 81: 16C-22C
        • Sossalla S.
        • Kallmeyer B.
        • Wagner S.
        • Mazur M.
        • Maurer U.
        • Toischer K.
        • Schmitto J.D.
        • Seipelt R.
        • Schöndube F.A.
        • Hasenfuss G.
        • Belardinelli L.
        • Maier L.S.
        Altered Na(+) currents in atrial fibrillation effects of ranolazine on arrhythmias and contractility in human atrial myocardium.
        J Am Coll Cardiol. 2010; 55: 2330-2342
        • Sicouri S.
        • Glass A.
        • Belardinelli L.
        • Antzelevitch C.
        Antiarrhythmic effects of ranolazine in canine pulmonary vein sleeve preparations.
        Heart Rhythm. 2008; 5: 1019-1026
        • Burashnikov A.
        • Di Diego J.M.
        • Zygmunt A.C.
        • Belardinelli L.
        • Antzelevitch C.
        Atrium-selective sodium channel block as a strategy for suppression of atrial fibrillation: differences in sodium channel inactivation between atria and ventricles and the role of ranolazine.
        Circulation. 2007; 116: 1449-1457
        • Kumar K.
        • Nearing B.D.
        • Carvas M.
        • Nascimento B.C.
        • Acar M.
        • Belardinelli L.
        • Verrier R.L.
        Ranolazine exerts potent effects on atrial electrical properties and abbreviates atrial fibrillation duration in the intact porcine heart.
        J Cardiovasc Electrophysiol. 2009; 20: 796-802
        • Kodama I.
        • Kamiya K.
        • Toyama J.
        Amiodarone: ionic and cellular mechanisms of action of the most promising class III agent.
        Am J Cardiol. 1999; 84: 20R-28R
        • Zygmunt A.C.
        • Nesterenko V.V.
        • Rajamani S.
        • Hu D.
        • Baras-Martinez H.
        • Belardinelli L.
        • Antzelevitch C.
        Mechanisms of atrial-selective block of Na+ channels by ranolazine: I.
        Am J Physiol Heart Circ Physiol. 2011; 301: H1606-H1614
        • Iwasaki Y.K.
        • Nishida K.
        • Kato T.
        • Nattel S.
        Atrial fibrillation pathophysiology: implications for management.
        Circulation. 2011; 124: 2264-2274
        • Murdock D.K.
        • Kersten M.
        • Kaliebe J.
        • Larrain G.
        The use of oral ranolazine to convert new or paroxysmal atrial fibrillation: a review of experience with implications for possible “pill in the pocket” approach to atrial fibrillation.
        Indian Pacing Electrophysiol J. 2009; 9: 260-267
        • Murdock D.K.
        • Reiffel J.A.
        • Kaliebe J.
        • Larrain G.
        The conversion of paroxysmal or initial onset atrial fibrillation with oral ranolazine: implications for a new “pill-in-pocket” approach in structural heart disease.
        J Atr Fibrillation. 2010; 2: 705-710
        • Chaitman B.R.
        Ranolazine for the treatment of chronic angina and potential use in other cardiovascular conditions.
        Circulation. 2006; 113: 2462-2472
        • Wu L.
        • Ma J.
        • Li H.
        • Wang C.
        • Grandi E.
        • Zhang P.
        • Luo A.
        • Bers D.M.
        • Shryock J.C.
        • Belardinelli L.
        Late sodium current contributes to the reverse rate-dependent effect of IKr inhibition on ventricular repolarization.
        Circulation. 2011; 123: 1713-1720
        • Orth P.M.
        • Hesketh J.C.
        • Mak C.K.
        • Yang Y.
        • Lin S.
        • Beatch G.N.
        • Ezrin A.M.
        • Fedida D.
        Rsd1235 blocks late INa and suppresses early afterdepolarizations and torsades de pointes induced by class III agents.
        Cardiovasc Res. 2006; 70: 486-496
        • Koren M.J.
        • Crager M.R.
        • Sweeney M.
        Long-term safety of a novel antianginal agent in patients with severe chronic stable angina: the Ranolazine Open Label Experience (ROLE).
        J Am Coll Cardiol. 2007; 49: 1027-1034
        • Morrow D.A.
        • Scirica B.M.
        • Karwatowska-Prokopczuk E.
        • Murphy S.A.
        • Budaj A.
        • Varshavsky S.
        • Wolff A.A.
        • Skene A.
        • McCabe C.H.
        • Braunwald E.
        • MERLIN-TIMI 36 Trial Investigators
        Effects of ranolazine on recurrent cardiovascular events in patients with non-ST-elevation acute coronary syndromes: the MERLIN-TIMI 36 randomized trial.
        JAMA. 2007; 297: 1775-1783
        • Stone P.H.
        • Gratsiansky N.A.
        • Blokhin A.
        • Huang I.Z.
        • Meng L.
        • ERICA Investigators
        Antianginal efficacy of ranolazine when added to treatment with amlodipine: the ERICA (Efficacy of Ranolazine in Chronic Angina) trial.
        J Am Coll Cardiol. 2006; 48: 566-575
        • European Medicines Agency
        European public assessment report for Ranexa.
        (Accessed April 23, 2012)