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Erschienen in: Cardiovascular Drugs and Therapy 6/2018

25.09.2018 | ORIGINAL ARTICLE

Amiodarone plus Ranolazine for Conversion of Post-Cardiac Surgery Atrial Fibrillation: Enhanced Effectiveness in Reduced Versus Preserved Ejection Fraction Patients

verfasst von: Vasilios Simopoulos, Athanasios Hevas, Apostolia Hatziefthimiou, Konstantina Dipla, Ioannis Skoularigis, Nikolaos Tsilimingas, Isaac Aidonidis

Erschienen in: Cardiovascular Drugs and Therapy | Ausgabe 6/2018

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Abstract

Purpose

Ranolazine (RAN) added to amiodarone (AMIO) has been shown to accelerate termination of postoperative atrial fibrillation (POAF) following coronary artery bypass surgery in patients without heart failure (HF). This study aimed to investigate if treatment efficacy with AMIO or AMIO + RAN differs between patients with concomitant HF with reduced or preserved ejection fraction (HFrEF or HFpEF).

Methods

Patients with POAF and HFrEF (n = 511, 446 males; 65 ± 9 years) and with HFpEF (n = 301, 257 males; 66 ± 10 years) were enrolled. Onset of AF occurred 2.15 ± 1.0 days after cardiac surgery, and patients within each group were randomly assigned to receive either AMIO monotherapy (300 mg in 30 min + 1125 mg in 36 h iv) or AMIO+RAN combination (500 mg po + 375 mg, after 6 h and 375 mg twice daily thereafter). Primary endpoint was the time to conversion of POAF within 36 h after initiation of treatment.

Results

AMIO restored sinus rhythm earlier in HFrEF vs. in HFpEF patients (24.3 ± 4.6 vs. 26.8 ± 2.8 h, p < 0.0001). AMIO + RAN converted POAF faster than AMIO alone in both HFrEF and HFpEF groups, with conversion times 10.4 ± 4.5 h in HFrEF and 12.2 ± 1.1 h in HFpEF patients (p < 0.0001). Left atrial diameter was significantly greater in HFrEF vs. HFpEF patients (48.2 ± 2.6 vs. 35.2 ± 2.9 mm, p < 0.0001). No serious adverse drug effects were observed during AF or after restoration to sinus rhythm in any of the patients enrolled.

Conclusion

AMIO alone or in combination with RAN converted POAF faster in patients with reduced EF than in those with preserved EF. Thus, AMIO + RAN seems to be a valuable alternative treatment for terminating POAF in HFrEF patients.
Literatur
1.
Zurück zum Zitat Tagarakis GI, Aidonidis I, Daskalopoulou SS, et al. Effect of ranolazine in preventing postoperative atrial fibrillation in patients undergoing coronary revascularization surgery. Curr Vasc Pharmacol. 2013;11(6):988–91.CrossRef Tagarakis GI, Aidonidis I, Daskalopoulou SS, et al. Effect of ranolazine in preventing postoperative atrial fibrillation in patients undergoing coronary revascularization surgery. Curr Vasc Pharmacol. 2013;11(6):988–91.CrossRef
2.
Zurück zum Zitat Lee SH, Kang DR, Uhm JS, Shim J, Sung JH, Kim JY, et al. New-onset atrial fibrillation predicts long-term newly developed atrial fibrillation after coronary artery bypass graft. Am Heart J. 2014;167(4):593–600.CrossRef Lee SH, Kang DR, Uhm JS, Shim J, Sung JH, Kim JY, et al. New-onset atrial fibrillation predicts long-term newly developed atrial fibrillation after coronary artery bypass graft. Am Heart J. 2014;167(4):593–600.CrossRef
3.
Zurück zum Zitat Guerra F, Romandini A, Barbarossa A, Belardinelli L, Capucci A. Ranolazine for rhythm control in atrial fibrillation: a systematic review and meta-analysis. Int J Cardiol. 2017;15(227):284–91.CrossRef Guerra F, Romandini A, Barbarossa A, Belardinelli L, Capucci A. Ranolazine for rhythm control in atrial fibrillation: a systematic review and meta-analysis. Int J Cardiol. 2017;15(227):284–91.CrossRef
4.
Zurück zum Zitat Fragakis N, Koskinas KC, Katritsis DG, Pagourelias ED, Zografos T, Geleris P. Comparison of effectiveness of ranolazine plus amiodarone versus amiodarone alone for conversion of recent-onset atrial fibrillation. Am J Cardiol. 2012;110(5):673–7.CrossRef Fragakis N, Koskinas KC, Katritsis DG, Pagourelias ED, Zografos T, Geleris P. Comparison of effectiveness of ranolazine plus amiodarone versus amiodarone alone for conversion of recent-onset atrial fibrillation. Am J Cardiol. 2012;110(5):673–7.CrossRef
5.
Zurück zum Zitat Koskinas KC, Fragakis N, Katritsis D, Skeberis V, Vassilikos V. Ranolazine enhances the efficacy of amiodarone for conversion of recent-onset atrial fibrillation. Europace. 2014;16(7):973–9.CrossRef Koskinas KC, Fragakis N, Katritsis D, Skeberis V, Vassilikos V. Ranolazine enhances the efficacy of amiodarone for conversion of recent-onset atrial fibrillation. Europace. 2014;16(7):973–9.CrossRef
6.
Zurück zum Zitat Simopoulos V, Tagarakis GI, Daskalopoulou SS, Daskalopoulos ME, Lenos A, Chryssagis K, et al. Ranolazine enhances the antiarrhythmic activity of amiodarone by accelerating conversion of new-onset atrial fibrillation after cardiac surgery. Angiology. 2014;65(4):294–7.CrossRef Simopoulos V, Tagarakis GI, Daskalopoulou SS, Daskalopoulos ME, Lenos A, Chryssagis K, et al. Ranolazine enhances the antiarrhythmic activity of amiodarone by accelerating conversion of new-onset atrial fibrillation after cardiac surgery. Angiology. 2014;65(4):294–7.CrossRef
7.
Zurück zum Zitat Burashnikov A, Di Diego JM, Barajas-Martínez H, et al. Ranolazine effectively suppresses atrial fibrillation in the setting of heart failure. Circ Heart Fail. 2014;7(4):627–33.CrossRef Burashnikov A, Di Diego JM, Barajas-Martínez H, et al. Ranolazine effectively suppresses atrial fibrillation in the setting of heart failure. Circ Heart Fail. 2014;7(4):627–33.CrossRef
8.
Zurück zum Zitat Tsanaxidis N, Aidonidis I, Hatziefthimiou A, et al. Ranolazine added to amiodarone facilitates earlier conversion of atrial fibrillation compared to amiodarone-only therapy. Pacing Clin Electrophysiol. 2017;40(4):372–8.CrossRef Tsanaxidis N, Aidonidis I, Hatziefthimiou A, et al. Ranolazine added to amiodarone facilitates earlier conversion of atrial fibrillation compared to amiodarone-only therapy. Pacing Clin Electrophysiol. 2017;40(4):372–8.CrossRef
9.
Zurück zum Zitat Zygmunt AC, Nesterenko VV, Rajamani S, Hu D, Barajas-Martinez H, Belardinelli L, et al. Mechanisms of atrial-selective block of Na+ channels by ranolazine: I. experimental analysis of the use-dependent block. Am J Physiol Heart Circ Physiol. 2011;301(4):H1606–14.CrossRef Zygmunt AC, Nesterenko VV, Rajamani S, Hu D, Barajas-Martinez H, Belardinelli L, et al. Mechanisms of atrial-selective block of Na+ channels by ranolazine: I. experimental analysis of the use-dependent block. Am J Physiol Heart Circ Physiol. 2011;301(4):H1606–14.CrossRef
10.
Zurück zum Zitat Burashnikov A, Di Diego JM, Zygmunt AC, 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(13):1449–57.CrossRef Burashnikov A, Di Diego JM, Zygmunt AC, 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(13):1449–57.CrossRef
11.
Zurück zum Zitat Antzelevitch C, Burashnikov A, Sicouri S, Belardinelli L. Electrophysiologic basis for the antiarrhythmic actions of ranolazine. Heart Rhythm. 2011;8(8):1281–90.CrossRef Antzelevitch C, Burashnikov A, Sicouri S, Belardinelli L. Electrophysiologic basis for the antiarrhythmic actions of ranolazine. Heart Rhythm. 2011;8(8):1281–90.CrossRef
12.
Zurück zum Zitat Burashnikov A, Belardinelli L, Antzelevitch C. Atrial-selective sodium channel block strategy to suppress atrial fibrillation: ranolazine versus propafenone. J Pharmacol Exp Ther. 2012;340(1):161–8.CrossRef Burashnikov A, Belardinelli L, Antzelevitch C. Atrial-selective sodium channel block strategy to suppress atrial fibrillation: ranolazine versus propafenone. J Pharmacol Exp Ther. 2012;340(1):161–8.CrossRef
13.
Zurück zum Zitat Suzuki T, Morishima M, Kato S, Ueda N, Honjo H, Kamiya K. Atrial selectivity in Na+ channel blockade by acute amiodarone. Cardiovasc Res. 2013;98(1):136–44.CrossRef Suzuki T, Morishima M, Kato S, Ueda N, Honjo H, Kamiya K. Atrial selectivity in Na+ channel blockade by acute amiodarone. Cardiovasc Res. 2013;98(1):136–44.CrossRef
14.
Zurück zum Zitat 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(1):88–95.CrossRef 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(1):88–95.CrossRef
15.
Zurück zum Zitat Burashnikov A, Sicouri S, Di Diego JM, Belardinelli L, Antzelevitch C. Synergistic effect of the combination of ranolazine and dronedarone to suppress atrial fibrillation. J Am Coll Cardiol. 2010;56(15):1216–24.CrossRef Burashnikov A, Sicouri S, Di Diego JM, Belardinelli L, Antzelevitch C. Synergistic effect of the combination of ranolazine and dronedarone to suppress atrial fibrillation. J Am Coll Cardiol. 2010;56(15):1216–24.CrossRef
16.
Zurück zum Zitat Bhimani AA, Yasuda T, Sadrpour SA, Khrestian CM, Lee S, Zeng D, et al. Ranolazine terminates atrial flutter and fibrillation in a canine model. Heart Rhythm. 2014;11(9):1592–9.CrossRef Bhimani AA, Yasuda T, Sadrpour SA, Khrestian CM, Lee S, Zeng D, et al. Ranolazine terminates atrial flutter and fibrillation in a canine model. Heart Rhythm. 2014;11(9):1592–9.CrossRef
17.
Zurück zum Zitat Frommeyer G, Schmidt M, Clauß C, Kaese S, Stypmann J, Pott C, et al. Further insights into the underlying electrophysiological mechanisms for reduction of atrial fibrillation by ranolazine in an experimental model of chronic heart failure. Eur J Heart Fail. 2012;14(12):1322–31.CrossRef Frommeyer G, Schmidt M, Clauß C, Kaese S, Stypmann J, Pott C, et al. Further insights into the underlying electrophysiological mechanisms for reduction of atrial fibrillation by ranolazine in an experimental model of chronic heart failure. Eur J Heart Fail. 2012;14(12):1322–31.CrossRef
18.
Zurück zum Zitat Maltsev VA, Silverman N, Sabbah HN, Undrovinas AI. Chronic heart failure slows late sodium current in human and canine ventricular myocytes: implications for repolarization variability. Eur J Heart Fail. 2007;9(3):219–27.CrossRef Maltsev VA, Silverman N, Sabbah HN, Undrovinas AI. Chronic heart failure slows late sodium current in human and canine ventricular myocytes: implications for repolarization variability. Eur J Heart Fail. 2007;9(3):219–27.CrossRef
19.
Zurück zum Zitat Undrovinas NA, Maltsev VA, Belardinelli L, Sabbah HN, Undrovinas A. Late sodium current contributes to diastolic cell Ca2+ accumulation in chronic heart failure. J Physiol Sci. 2010;60(4):245–57.CrossRef Undrovinas NA, Maltsev VA, Belardinelli L, Sabbah HN, Undrovinas A. Late sodium current contributes to diastolic cell Ca2+ accumulation in chronic heart failure. J Physiol Sci. 2010;60(4):245–57.CrossRef
20.
Zurück zum Zitat Tsu LV, Lee S. Use of ranolazine in the prevention and treatment of postoperative atrial fibrillation in patients undergoing cardiac surgery. Ann Pharmacother. 2014;48(5):633–7.CrossRef Tsu LV, Lee S. Use of ranolazine in the prevention and treatment of postoperative atrial fibrillation in patients undergoing cardiac surgery. Ann Pharmacother. 2014;48(5):633–7.CrossRef
21.
Zurück zum Zitat Miles RH, Passman R, Murdock DK. Comparison of effectiveness and safety of ranolazine versus amiodarone for preventing atrial fibrillation after coronary artery bypass grafting. Am J Cardiol. 2011;108(5):673–6.CrossRef Miles RH, Passman R, Murdock DK. Comparison of effectiveness and safety of ranolazine versus amiodarone for preventing atrial fibrillation after coronary artery bypass grafting. Am J Cardiol. 2011;108(5):673–6.CrossRef
22.
Zurück zum Zitat Hammond DA, Smotherman C, Jankowski CA, Tan S, Osian O, Kraemer D, et al. Short-course of ranolazine prevents postoperative atrial fibrillation following coronary artery bypass grafting and valve surgeries. Clin Res Cardiol. 2015;104(5):410–7.CrossRef Hammond DA, Smotherman C, Jankowski CA, Tan S, Osian O, Kraemer D, et al. Short-course of ranolazine prevents postoperative atrial fibrillation following coronary artery bypass grafting and valve surgeries. Clin Res Cardiol. 2015;104(5):410–7.CrossRef
Metadaten
Titel
Amiodarone plus Ranolazine for Conversion of Post-Cardiac Surgery Atrial Fibrillation: Enhanced Effectiveness in Reduced Versus Preserved Ejection Fraction Patients
verfasst von
Vasilios Simopoulos
Athanasios Hevas
Apostolia Hatziefthimiou
Konstantina Dipla
Ioannis Skoularigis
Nikolaos Tsilimingas
Isaac Aidonidis
Publikationsdatum
25.09.2018
Verlag
Springer US
Erschienen in
Cardiovascular Drugs and Therapy / Ausgabe 6/2018
Print ISSN: 0920-3206
Elektronische ISSN: 1573-7241
DOI
https://doi.org/10.1007/s10557-018-6832-8

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