Gaetano M De Ferrari1, Lars S Maier2, Lluís Mont3, Peter J Schwartz4, Gregor Simonis5, Matthias Leschke6, Edoardo Gronda7, Giuseppe Boriani8, Harald Darius9, Laura Guillamón Torán10, Irene Savelieva11, Veronica Dusi12, Niccolò Marchionni13, Miguel Quintana Rendón14, Kai Schumacher15, Giulia Tonini16, Lorenzo Melani17, Stefano Giannelli16, Carlo Alberto Maggi16, A John Camm11. 1. Department of Cardiology and Cardiovascular Clinical Research Center, Fondazione IRCCS Policlinico San Matteo, and Department of Molecular Medicine, University of Pavia, Pavia, Italy. Electronic address: g.deferrari@smatteo.pv.it. 2. Klinik und Poliklinik für Innere Medizin II, Universitätsklinikum Regensburg, Regensburg, Germany. 3. Department of Cardiology, Thorax Institute Hospital Clinic, Universitat de Barcelona, Barcelona, Catalonia, Spain. 4. Center for Cardiac Arrhythmias of Genetic Origin-IRCCS Istituto Auxologico Italiano, Milan, Italy. 5. Praxisklinik Herz und Gefäße, Dresden, Germany. 6. Klinikum Esslingen GmbH, Abteilung Kardiologie, Esslingen, Germany. 7. IRCCS MultiMedica, Milan, Italy. 8. Ospedale S. Orsola-Malpighi, Dipartimento di Cardiologia, Bologna, Italy. 9. Vivantes Klinikum Neukölln, Berlin, Germany. 10. Corporació Sanitària Parc Taulí de Sabadell, Sabadell, Spain. 11. St. George's University, London, United Kingdom. 12. Department of Cardiology, Fondazione IRCCS Policlinico San Matteo, Pavia and University of Pavia, Italy. 13. Division of Geriatric Cardiology and Medicine, Azienda Ospedaliero-Universitaria Careggi, Florence, Italy. 14. The Karolinska Institute at Hospital de Torrevieja, Servicio de Cardiología, Alicante, Spain. 15. Menarini Research & Business Service GmbH, Berlin, Germany. 16. Menarini Ricerche S.p.A, Florence, Italy. 17. Menarini Industrie Farmaceutiche Riunite s.r.l, Florence, Italy.
Abstract
BACKGROUND: Currently available antiarrhythmic agents for the treatment of atrial fibrillation (AF) have important limitations, leaving an unmet need for safe and effective therapy. Ranolazine is an approved antianginal agent with a favorable safety profile and electrophysiologic properties suggesting a potential role in the treatment of AF. OBJECTIVE: The purpose of this study was to assess the safety and efficacy of ranolazine in the prevention of AF recurrence after successful electrical cardioversion and to ascertain the most appropriate dose of this agent. METHODS: This prospective, multicenter, randomized, double-blind, placebo-control parallel group phase II dose-ranging trial randomized patients with persistent AF (7 days to 6 months) 2 hours after successful electrical cardioversion to placebo, or ranolazine 375 mg, 500 mg, or 750 mg bid. Patients were monitored daily by transtelephonic ECG. The primary end-point was the time to first AF recurrence. RESULTS: Of 241 patients randomized, 238 took at least 1 drug dose. Ranolazine proved to be safe and tolerable. No dose of the drug significantly prolonged time to AF recurrence. AF recurred in 56.4%, 56.9%, 41.7%, and 39.7% of patients in the placebo, ranolazine 375 mg, ranolazine 500 mg, and ranolazine 750 mg groups, respectively. The reduction in overall AF recurrence in the combined 500-mg and 750-mg groups was of borderline significance compared to the placebo group (P = .053) and significant compared to 375-mg group (P = .035). CONCLUSION: No dose of ranolazine significantly prolonged time to AF recurrence. However, the 500-mg and 750 mg-groups combined reduced AF recurrences, suggesting a possible role for this agent in the treatment of AF.
RCT Entities:
BACKGROUND: Currently available antiarrhythmic agents for the treatment of atrial fibrillation (AF) have important limitations, leaving an unmet need for safe and effective therapy. Ranolazine is an approved antianginal agent with a favorable safety profile and electrophysiologic properties suggesting a potential role in the treatment of AF. OBJECTIVE: The purpose of this study was to assess the safety and efficacy of ranolazine in the prevention of AF recurrence after successful electrical cardioversion and to ascertain the most appropriate dose of this agent. METHODS: This prospective, multicenter, randomized, double-blind, placebo-control parallel group phase II dose-ranging trial randomized patients with persistent AF (7 days to 6 months) 2 hours after successful electrical cardioversion to placebo, or ranolazine 375 mg, 500 mg, or 750 mg bid. Patients were monitored daily by transtelephonic ECG. The primary end-point was the time to first AF recurrence. RESULTS: Of 241 patients randomized, 238 took at least 1 drug dose. Ranolazine proved to be safe and tolerable. No dose of the drug significantly prolonged time to AF recurrence. AF recurred in 56.4%, 56.9%, 41.7%, and 39.7% of patients in the placebo, ranolazine 375 mg, ranolazine 500 mg, and ranolazine 750 mg groups, respectively. The reduction in overall AF recurrence in the combined 500-mg and 750-mg groups was of borderline significance compared to the placebo group (P = .053) and significant compared to 375-mg group (P = .035). CONCLUSION: No dose of ranolazine significantly prolonged time to AF recurrence. However, the 500-mg and 750 mg-groups combined reduced AF recurrences, suggesting a possible role for this agent in the treatment of AF.
Authors: Amara Greer-Short; Hassan Musa; Katherina M Alsina; Li Ni; Tarah A Word; Julia O Reynolds; Daniel Gratz; Cemantha Lane; Mona El-Refaey; Sathya Unudurthi; Michel Skaf; Ning Li; Vadim V Fedorov; Xander H T Wehrens; Peter J Mohler; Thomas J Hund Journal: Heart Rhythm Date: 2019-10-14 Impact factor: 6.343
Authors: Anh Tuan Ton; William Nguyen; Katrina Sweat; Yannick Miron; Eduardo Hernandez; Tiara Wong; Valentyna Geft; Andrew Macias; Ana Espinoza; Ky Truong; Lana Rasoul; Alexa Stafford; Tamara Cotta; Christina Mai; Tim Indersmitten; Guy Page; Paul E Miller; Andre Ghetti; Najah Abi-Gerges Journal: Sci Rep Date: 2021-06-08 Impact factor: 4.379