Ranolazine enhances the efficacy of amiodarone for conversion of recent-onset atrial fibrillation
Open accessAbstract
AIMS: Amiodarone is used commonly for pharmacological cardioversion of atrial fibrillation (AF), but it is limited by moderate efficacy and delayed action. Ranolazine and amiodarone are markedly synergistic in suppressing experimental AF in vitro, yet the clinical efficacy of ranolazine combined with amiodarone for AF conversion has only undergone minimal investigation. This prospective, single-blinded, randomized study compared the safety and efficacy of ranolazine added to amiodarone vs. amiodarone alone for conversion of recent-onset AF. METHODS AND RESULTS: We enroled 121 patients (64 ± 10 years, 45% male) with recent-onset (<48 h duration) AF who were eligible for pharmacological cardioversion. Patients received either 24 h amiodarone infusion (loading dose 5 mg/kg followed by maintenance dose of 50 mg/h; n = 60), or amiodarone infusion at the same dosage plus a single oral dose of ranolazine 1500 mg (n = 61). Patients in the amiodarone plus ranolazine group compared with the amiodarone-only group showed significantly higher conversion rates at 24 h (87 vs. 70%, respectively; P = 0.024) and at 12 h (52 vs. 32%; P = 0.021), and shorter time to conversion (10.2 ± 3.3 vs. 13.3 ± 4.1 h; P = 0.001). Subgroup analysis identified higher 24 h conversion in patients with left atrial (LA) diameter >46 mm who received the combination treatment vs. amiodarone alone (81 vs. 54%; P = 0.02), whereas the efficacy of the two interventions did not differ among patients with LA diameter ≤46 mm (P = 0.77). There was modest QT prolongation in both the groups, no serious adverse reactions, and no pro-arrhythmic events. CONCLUSION: Addition of ranolazine to amiodarone was safe and well tolerated in this study, and it demonstrated efficacy superior to amiodarone alone for conversion of recent-onset AF. These findings may have clinical implications by offering a simple therapeutic manoeuvre to enhance amiodarone's effectiveness for conversion of AF.
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Small, open-label studies suggest that ranolazine might enhance the antiarrhythmic effect of amiodarone for cardioversion.
“Small, open-label studies suggest that ranolazine might enhance the antiarrhythmic effect of amiodarone for cardioversion, 681-683”
From 2016 ESC Guidelines for the management of atrial fibrillation developed in collaboration with EACTS (2016) · cites this paper as [683]
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Cites
Guidelines for the management of atrial fibrillation
Authors/Task Force Members, Camm, A. J., Kirchhof, P. F., Lip, G. Y. H., Schotten, U., Savelieva, I., Ernst, S., Gelder, I. C. V., Al‐Attar, N., Hindricks, G., et al. (2010) · European Heart Journal · doi:10.1093/eurheartj/ehq278 · Cited by 5,875 · see citing works
2012 focused update of the ESC Guidelines for the management of atrial fibrillation
Authors Task Force Members, Camm, A. J., Lip, G. Y. H., Caterina, R. D., Savelieva, I., Atar, D., Hohnloser, S. H., Hindricks, G., Kirchhof, P. F., Bax, J. J., et al. (2012) · EP Europace · doi:10.1093/europace/eus305 · Cited by 3,814 · see citing works
Guidelines for the management of atrial fibrillation
Authors/Task Force Members, Camm, A. J., Kirchhof, P. F., Lip, G. Y. H., Schotten, U., Savelieva, I., Ernst, S., Gelder, I. C. V., Al‐Attar, N., Hindricks, G., et al. (2010) · EP Europace · doi:10.1093/europace/euq350 · Cited by 1,749 · see citing works
Abhayaratna, W. P., Seward, J. B., Appleton, C. P., Douglas, P. S., Oh, J. K., Tajik, A. J., & Tsang, T. S. M. (2006) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2006.02.048 · Cited by 1,075 · see citing works
2012 Focused Update of the ESC Guidelines for the Management of Atrial Fibrillation
Camm, A. J., Lip, G. Y. H., Caterina, R. D., Savelieva, I., Atar, D., Hohnloser, S. H., Hindricks, G., & Kirchhof, P. F. (2012) · Revista Española de Cardiología (English Edition) · doi:10.1016/j.rec.2012.11.003 · Cited by 687 · see citing works
Electrophysiological Effects of Ranolazine, a Novel Antianginal Agent With Antiarrhythmic Properties
Antzelevitch, C. N., Belardinelli, L., Zygmunt, A. C., Burashnikov, A., Diego, J. M. D., Fish, J. M., Cordeiro, J. M., & Thomas, G. (2004) · Circulation · doi:10.1161/01.cir.0000139333.83620.5d · Cited by 674 · see citing works
Camm, A. J., Kirchhof, P. F., Lip, G. Y. H., Schotten, U., Savelieva, I., Ernst, S., Gelder, I. C. V., Al‐Attar, N., Hindricks, G., Prendergast, B., et al. (2011) · European Heart Journal · doi:10.1093/eurheartj/ehq512 · Cited by 555 · see citing works
Ravelli, F., & Allessie, M. A. (1997) · Circulation · doi:10.1161/01.cir.96.5.1686 · Cited by 478 · see citing works
Scirica, B. M., Morrow, D. A., Hod, H., Murphy, S. A., Belardinelli, L., Hedgepeth, C. M., Molhoek, P. G., Verheugt, F. W. A., Gersh, B. J., McCabe, C. H., et al. (2007) · Circulation · doi:10.1161/circulationaha.107.724880 · Cited by 444 · see citing works
Atrium-Selective Sodium Channel Block as a Strategy for Suppression of Atrial Fibrillation
Burashnikov, A., Diego, J. M. D., Zygmunt, A. C., Belardinelli, L., & Antzelevitch, C. N. (2007) · Circulation · doi:10.1161/circulationaha.107.704890 · Cited by 399 · see citing works
Antianginal Efficacy of Ranolazine When Added to Treatment With Amlodipine
Stone, P. H., Gratsiansky, N. A., Blokhin, A., Huang, I., & Meng, L. (2006) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2006.05.044 · Cited by 353 · see citing works
Verheule, S., Wilson, E., Everett, T. H., Shanbhag, S. M., Golden, C. L., & Olgin, J. E. (2003) · Circulation · doi:10.1161/01.cir.0000066915.15187.51 · Cited by 336 · see citing works
Altered Na+Currents in Atrial Fibrillation
Sossalla, S. T., Kallmeyer, B., Wagner, S., Mazur, M. J., Maurer, U., Toischer, K., Schmitto, J. D., Seipelt, R. G., Schöndube, F. A., Hasenfuss, G. P., et al. (2010) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2009.12.055 · Cited by 272 · see citing works
Tachycardia-Induced Changes in Na+Current in a Chronic Dog Model of Atrial Fibrillation
Gaspo, R., BOSCH, R. F., Bou‐Abboud, E., & Nattel, S. (1997) · Circulation Research · doi:10.1161/01.res.81.6.1045 · Cited by 256 · see citing works
Chevalier, P., Durand-Dubief, A., Burri, H., Cucherat, M., Kirkorian, G., & Touboul, P. (2003) · Journal of the American College of Cardiology · doi:10.1016/s0735-1097(02)02705-5 · Cited by 184 · see citing works
Pisters, R., Nieuwlaat, R., Prins, M. H., Heuzey, J. Y. L., Maggioni, A. P., Camm, A. J., Crijns, H. J. G. M., & for the Euro Heart Survey Investigators (2012) · EP Europace · doi:10.1093/europace/eur406 · Cited by 150 · see citing works
Synergistic Effect of the Combination of Ranolazine and Dronedarone to Suppress Atrial Fibrillation
Burashnikov, A., Sicouri, S., Diego, J. M. D., Belardinelli, L., & Antzelevitch, C. N. (2010) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2010.08.600 · Cited by 131 · see citing works
Savelieva, I., & Camm, A. J. (2008) · EP Europace · doi:10.1093/europace/eun130 · Cited by 125 · see citing works
Antiarrhythmic effects of ranolazine in canine pulmonary vein sleeve preparations
Sicouri, S., Glass, A. M., Belardinelli, L., & Antzelevitch, C. N. (2008) · Heart Rhythm · doi:10.1016/j.hrthm.2008.03.018 · Cited by 120 · see citing works
ORTH, P., HESKETH, J., MAK, C., YANG, Y., Lin, S., Beatch, G. N., Ezrin, A. M., & Fedida, D. (2006) · Cardiovascular Research · doi:10.1016/j.cardiores.2006.01.026 · Cited by 117 · see citing works
Long-Term Safety of a Novel Antianginal Agent in Patients With Severe Chronic Stable Angina
Koren, M. J., Crager, M., & Sweeney, M. L. (2007) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2006.10.067 · Cited by 115 · see citing works
Miles, R. H., PASSMAN, R. S., & Murdock, D. K. (2011) · The American Journal of Cardiology · doi:10.1016/j.amjcard.2011.04.017 · Cited by 105 · see citing works
Kumar, K., Nearing, B. D., Carvas, M., Nascimento, B., Acar, M., Belardinelli, L., & Verrier, R. L. (2009) · Journal of Cardiovascular Electrophysiology · doi:10.1111/j.1540-8167.2009.01437.x · Cited by 105 · see citing works
Antoons, G., Oros, A., Beekman, J. D. M., et al. (2010) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2009.10.033 · Cited by 97 · see citing works
Amiodarone for pharmacological cardioversion of recent-onset atrial fibrillation
Khan, I. A., Mehta, N. J., & Gowda, R. M. (2003) · International Journal of Cardiology · doi:10.1016/s0167-5273(02)00477-1 · Cited by 94 · see citing works
The effect of ranolazine on maintaining sinus rhythm in patients with resistant atrial fibrillation.
Murdock, D. K., Overton, N., Kersten, M., et al. (2008) · PubMed · Cited by 85 · see citing works
Fragakis, N., Koskinas, K. C., Katritsis, D. G., Pagourelias, E. D., Zografos, T., & Geleris, P. (2012) · The American Journal of Cardiology · doi:10.1016/j.amjcard.2012.04.044 · Cited by 82 · see citing works
Self-citationWang, G. K., Calderon, J., & Wang, S. (2007) · Molecular Pharmacology · doi:10.1124/mol.107.041541 · Cited by 78 · see citing works
Sicouri, S., Burashnikov, A., Belardinelli, L., & Antzelevitch, C. N. (2009) · Circulation Arrhythmia and Electrophysiology · doi:10.1161/circep.109.886275 · Cited by 76 · see citing works
KOCHIADAKIS, G. E., Igoumenidis, N. E., Hamilos, M. E., Marketou, M. E., CHLOUVERAKIS, G. I., & Vardas, P. E. (2007) · The American Journal of Cardiology · doi:10.1016/j.amjcard.2007.01.059 · Cited by 58 · see citing works
Atrial-selective sodium channel block as a novel strategy for the management of atrial fibrillation
Antzelevitch, C. N., & Burashnikov, A. (2009) · Journal of Electrocardiology · doi:10.1016/j.jelectrocard.2009.07.007 · Cited by 58 · see citing works
Murdock, D. K., Kaliebe, J., & Larrain, G. (2012) · Pacing and Clinical Electrophysiology · doi:10.1111/j.1540-8159.2011.03298.x · Cited by 57 · see citing works
Hernández‐Madrid, A., Svendsen, J. H., Lip, G. Y. H., Gelder, I. C. V., Dobreanu, D., & Blomström‐Lundqvist, C. (2013) · EP Europace · doi:10.1093/europace/eut143 · Cited by 51 · see citing works
Mechanisms of ranolazine's dual protection against atrial and ventricular fibrillation
Verrier, R. L., Kiran Kumar, K. C., Nieminen, T. V. M., & Belardinelli, L. (2012) · EP Europace · doi:10.1093/europace/eus380 · Cited by 51 · see citing works
Synergistic Action of Atrial Dilation and Sodium Channel Blockade on Conduction in Rabbit Atria
Eijsbouts, S. C. M., Houben, R. P. M., Blaauw, Y., et al. (2004) · Journal of Cardiovascular Electrophysiology · doi:10.1046/j.1540-8167.2004.04326.x · Cited by 44 · see citing works
Simopoulos, V., Tagarakis, G. I., Daskalopoulou, S. S., Daskalopoulos, M. E., Lenos, A., Chryssagis, K., Skoularingis, I., Molyvdas, P.-A., Tsilimingas, N. B., & Aidonidis, I. (2014) · Angiology · doi:10.1177/0003319713477911 · Cited by 43 · see citing works
Milberg, P., Frommeyer, G., Ghezelbash, S., et al. (2013) · EP Europace · doi:10.1093/europace/eus399 · Cited by 39 · see citing works
Karwatowska‐Prokopczuk, E., Wang, W., Cheng, M. L., Zeng, D., Schwartz, P. J., & Belardinelli, L. (2012) · EP Europace · doi:10.1093/europace/eus400 · Cited by 34 · see citing works
Emergency management of atrial fibrillation
Wakai, A., & O’Neill, J. (2003) · Postgraduate Medical Journal · doi:10.1136/pmj.79.932.313 · Cited by 34 · see citing works
Guo, D., Young, L. H., Wu, Y., Belardinelli, L., Kowey, P. R., & Yan, G. (2010) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.01145.2009 · Cited by 33 · see citing works
Frommeyer, G., Milberg, P., Uphaus, T., Kaiser, D., Kaese, S., BREITHARDT, G. E., & Eckardt, L. (2013) · Cardiovascular Therapeutics · doi:10.1111/1755-5922.12035 · Cited by 30 · see citing works
Murdock, D. K., Reiffel, J. A., Kaliebe, J., & Larrain, G. (2010) · Journal of Atrial Fibrillation · doi:10.4022/jafib.v2i1.572 · Cited by 29 · see citing works
Fragakis, N., PAPADOPOULOS, N., Papanastasiou, S., Kozirakis, M., MALIGKOS, G., Tsaritsaniotis, E., & Katsaris, G. (2005) · Pacing and Clinical Electrophysiology · doi:10.1111/j.1540-8159.2005.00212.x · Cited by 21 · see citing works
Self-citationAntiarrhythmic properties of ranolazine – from bench to bedside
Tzeis, S. E., & Andrikopoulos, G. K. (2012) · Expert Opinion on Investigational Drugs · doi:10.1517/13543784.2012.716826 · Cited by 12 · see citing works
Flagged first, then by citations
Research works printed but not linked: 1
- Scirica BM, Belardinelli L, Chaitman BR, Waks JW, Volo SC, Karwatowska- Prokopczuk E et al. Effect of ranolazine on atrial fibrillation among patients with non-ST elevation acute coronary syndromes (NSTEACS)-observations from the MERLIN-TIMI 36 Trial. Circulation 2011;124:A13798.
Cited by
Sorted by citations
2016 ESC Guidelines for the management of atrial fibrillation developed in collaboration with EACTS
Kirchhof, P., Benussi, S., Kotecha, D., Ahlsson, A., Atar, D., Casadei, B., Castella, M., Diener, H.-C., Heidbuchel, H., Hendriks, J., et al. (2016) · European Heart Journal · doi:10.1093/eurheartj/ehw210 · Cited by 6,418 · see citing works
2016 ESC Guidelines for the management of atrial fibrillation developed in collaboration with EACTS
Kirchhof, P., Benussi, S., Kotecha, D., Ahlsson, A., Atar, D., Casadei, B., Castella, M., Diener, H.-C., Heidbuchel, H., Hendriks, J., et al. (2016) · European Journal of Cardio-Thoracic Surgery · doi:10.1093/ejcts/ezw313 · Cited by 1,403 · see citing works
De Ferrari, G. M., Maier, L. S., Mont, L., Schwartz, P. J., Simonis, G., Leschke, M., Gronda, E., Boriani, G., Darius, H., Guillamón Torán, L., et al. (2015) · Heart Rhythm · doi:10.1016/j.hrthm.2015.01.021 · Cited by 87 · see citing works
Scirica, B. M., Belardinelli, L., Chaitman, B. R., Waks, J. W., Volo, S., Karwatowska-Prokopczuk, E., Murphy, S. A., Cheng, M. L., Braunwald, E., & Morrow, D. A. (2015) · Europace · doi:10.1093/europace/euu217 · Cited by 58 · see citing works
- Authors
- Koskinas, K. C., Fragakis, N., Katritsis, D., Skeberis, V., & Vassilikos, V.
- Affiliations
- Aristotle University of Thessaloniki (GR)
- Athens Euroclinic (GR)
- Corresponding author
- Koskinas, K. C.
- Venue
- Europace
- Publisher
- Oxford University Press (OUP)
- Published
- 2014-01-27
- Volume
- 16
- Issue
- 7
- Pages
- 973-979
- ISSN
- 1099-5129 (ISSN-L)
- 1532-2092
- OpenAlex
- W2104750871
- Cited by
- 72
- References
- 45
- Citations by year
- 2025: 3 · 2024: 5 · 2023: 3 · 2022: 3 · 2021: 7 · 2020: 11 · 2019: 3 · 2018: 7 · 2017: 4 · 2016: 14 · 2015: 7 · 2014: 5
- FWCI
- 6.86
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- EP Europace (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Atrial Fibrillation Management and Outcomes
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac Arrhythmias and Treatments
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac electrophysiology and arrhythmias
- Keywords
- ranolazine, amiodarone, atrial fibrillation, pharmacological cardioversion, recent-onset atrial fibrillation, combination therapy, left atrial diameter, QT prolongation, antiarrhythmic drugs
- MeSH terms
- Ranolazine, Acetanilides, Administration, Oral, Aged, Amiodarone, Anti-Arrhythmia Agents, Atrial Fibrillation, Drug Administration Schedule, Drug Synergism, Drug Therapy, Combination, Female, Greece, Heart Rate, Humans, Infusions, Intravenous, Male, Middle Aged, Piperazines, Prospective Studies, Time Factors, Single-Blind Method, Treatment Outcome
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