title: Ranolazine in the treatment of atrial fibrillation: Results of the dose-ranging RAFFAELLO (Ranolazine in Atrial Fibrillation Following An ELectricaL CardiOversion) study.
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).
  
  
  CONCLUSIONS
  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.affiliation: 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.
authors.forename: Gaetano M
authors.initials: GM
authors.lastname: De Ferrari
authors.affiliation: Klinik und Poliklinik für Innere Medizin II, Universitätsklinikum Regensburg, Regensburg, Germany.
authors.forename: Lars S
authors.initials: LS
authors.lastname: Maier
authors.affiliation: Department of Cardiology, Thorax Institute Hospital Clinic, Universitat de Barcelona, Barcelona, Catalonia, Spain.
authors.forename: Lluís
authors.initials: L
authors.lastname: Mont
authors.affiliation: Center for Cardiac Arrhythmias of Genetic Origin-IRCCS Istituto Auxologico Italiano, Milan, Italy.
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Schwartz
authors.affiliation: Praxisklinik Herz und Gefäße, Dresden, Germany.
authors.forename: Gregor
authors.initials: G
authors.lastname: Simonis
authors.affiliation: Klinikum Esslingen GmbH, Abteilung Kardiologie, Esslingen, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Leschke
authors.affiliation: IRCCS MultiMedica, Milan, Italy.
authors.forename: Edoardo
authors.initials: E
authors.lastname: Gronda
authors.affiliation: Ospedale S. Orsola-Malpighi, Dipartimento di Cardiologia, Bologna, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Boriani
authors.affiliation: Vivantes Klinikum Neukölln, Berlin, Germany.
authors.forename: Harald
authors.initials: H
authors.lastname: Darius
authors.affiliation: Corporació Sanitària Parc Taulí de Sabadell, Sabadell, Spain.
authors.forename: Laura
authors.initials: L
authors.lastname: Guillamón Torán
authors.affiliation: St. George's University, London, United Kingdom.
authors.forename: Irene
authors.initials: I
authors.lastname: Savelieva
authors.affiliation: Department of Cardiology, Fondazione IRCCS Policlinico San Matteo, Pavia and University of Pavia, Italy.
authors.forename: Veronica
authors.initials: V
authors.lastname: Dusi
authors.affiliation: Division of Geriatric Cardiology and Medicine, Azienda Ospedaliero-Universitaria Careggi, Florence, Italy.
authors.forename: Niccolò
authors.initials: N
authors.lastname: Marchionni
authors.affiliation: The Karolinska Institute at Hospital de Torrevieja, Servicio de Cardiología, Alicante, Spain.
authors.forename: Miguel
authors.initials: M
authors.lastname: Quintana Rendón
authors.affiliation: Menarini Research & Business Service GmbH, Berlin, Germany.
authors.forename: Kai
authors.initials: K
authors.lastname: Schumacher
authors.affiliation: Menarini Ricerche S.p.A, Florence, Italy.
authors.forename: Giulia
authors.initials: G
authors.lastname: Tonini
authors.affiliation: Menarini Industrie Farmaceutiche Riunite s.r.l, Florence, Italy.
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Melani
authors.affiliation: Menarini Ricerche S.p.A, Florence, Italy.
authors.forename: Stefano
authors.initials: S
authors.lastname: Giannelli
authors.affiliation: Menarini Ricerche S.p.A, Florence, Italy.
authors.forename: Carlo
authors.initials: C
authors.lastname: Alberto Maggi
authors.affiliation: St. George's University, London, United Kingdom.
authors.forename: A John
authors.initials: AJ
authors.lastname: Camm
mesh_terms: D000368:Aged; D001281:Atrial Fibrillation / Q000175:diagnosis / Q000188:drug therapy; D002317:Cardiovascular Agents / Q000008:administration & dosage / Q000009:adverse effects; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D016903:Drug Monitoring / Q000379:methods; D004554:Electric Countershock / Q000009:adverse effects / Q000379:methods; D015716:Electrocardiography, Ambulatory; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D000069458:Ranolazine / Q000008:administration & dosage / Q000009:adverse effects; D055502:Secondary Prevention / Q000379:methods*; D016896:Treatment Outcome
chemical_list: D002317:Cardiovascular Agents; D000069458:Ranolazine
keywords: Antiarrhythmic drug; Atrial fibrillation; Atrial flutter; Cardioversion; Electrophysiology; Randomized controlled trial; Ranolazine