دورية أكاديمية
Efficacy of Flecainide in the Treatment of Catecholaminergic Polymorphic Ventricular Tachycardia: A Randomized Clinical Trial.
| العنوان: | Efficacy of Flecainide in the Treatment of Catecholaminergic Polymorphic Ventricular Tachycardia: A Randomized Clinical Trial. |
|---|---|
| المؤلفون: | Kannankeril PJ; Thomas P. Graham Jr Division of Pediatric Cardiology, Department of Pediatrics, Monroe Carell Jr Children's Hospital at Vanderbilt, Vanderbilt Center for Arrhythmia Research and Therapeutics, Vanderbilt University Medical Center, Nashville, Tennessee., Moore JP; Department of Pediatrics, Division of Cardiology, UCLA (University of California, Los Angeles) Medical Center., Cerrone M; Leon H. Charney Division of Cardiology and Cardiovascular Genetics Program, New York University School of Medicine, New York City., Priori SG; Leon H. Charney Division of Cardiology and Cardiovascular Genetics Program, New York University School of Medicine, New York City., Kertesz NJ; Heart Center, Nationwide Children's Hospital, Department of Pediatrics, Division of Cardiology, Ohio State University, Columbus., Ro PS; Heart Center, Nationwide Children's Hospital, Department of Pediatrics, Division of Cardiology, Ohio State University, Columbus., Batra AS; Children's Hospital of Orange County, Department of Pediatrics, Division of Cardiology, University of California, Irvine., Kaufman ES; Heart and Vascular Research Center, MetroHealth Campus, Case Western Reserve University, Cleveland, Ohio., Fairbrother DL; Department of Pediatrics, Division of Cardiology, East Carolina University, Greenville, North Carolina., Saarel EV; Division of Pediatric Cardiology, Cleveland Clinic Children's Hospital, Cleveland, Ohio., Etheridge SP; Department of Pediatrics, Division of Cardiology, Primary Children's Hospital, University of Utah, Salt Lake City., Kanter RJ; Department of Pediatrics, Division of Cardiology, Duke University Medical Center, Durham, North Carolina., Carboni MP; Department of Pediatrics, Division of Cardiology, Duke University Medical Center, Durham, North Carolina., Dzurik MV; Heart Center, Cook Children's Healthcare, Fort Worth, Texas., Fountain D; Thomas P. Graham Jr Division of Pediatric Cardiology, Department of Pediatrics, Monroe Carell Jr Children's Hospital at Vanderbilt, Vanderbilt Center for Arrhythmia Research and Therapeutics, Vanderbilt University Medical Center, Nashville, Tennessee., Chen H; Department of Biostatistics, Vanderbilt University Medical Center, Nashville, Tennessee., Ely EW; Veteran's Affairs Tennessee Valley Geriatric Research Education Clinical Center, Nashville, Tennessee14Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee15Center for Health Services Research, Vanderbilt University Medical Center, Nashville, Tennessee., Roden DM; Thomas P. Graham Jr Division of Pediatric Cardiology, Department of Pediatrics, Monroe Carell Jr Children's Hospital at Vanderbilt, Vanderbilt Center for Arrhythmia Research and Therapeutics, Vanderbilt University Medical Center, Nashville, Tennessee14Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee16Department of Biomedical Informatics, Vanderbilt University Medical Center, Nashville, Tennessee17Department of Pharmacology, Vanderbilt University Medical Center, Nashville, Tennessee., Knollmann BC; Thomas P. Graham Jr Division of Pediatric Cardiology, Department of Pediatrics, Monroe Carell Jr Children's Hospital at Vanderbilt, Vanderbilt Center for Arrhythmia Research and Therapeutics, Vanderbilt University Medical Center, Nashville, Tennessee14Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee17Department of Pharmacology, Vanderbilt University Medical Center, Nashville, Tennessee. |
| المصدر: | JAMA cardiology [JAMA Cardiol] 2017 Jul 01; Vol. 2 (7), pp. 759-766. |
| نوع المنشور: | Journal Article; Randomized Controlled Trial; Research Support, N.I.H., Extramural |
| اللغة: | English |
| بيانات الدورية: | Publisher: American Medical Association Country of Publication: United States NLM ID: 101676033 Publication Model: Print Cited Medium: Internet ISSN: 2380-6591 (Electronic) NLM ISO Abbreviation: JAMA Cardiol Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: [Chicago, Illinois] : American Medical Association, [2016]- |
| مواضيع طبية MeSH: | Exercise*, Anti-Arrhythmia Agents/*therapeutic use , Flecainide/*therapeutic use , Tachycardia, Ventricular/*drug therapy, Adolescent ; Adrenergic beta-Antagonists/therapeutic use ; Cross-Over Studies ; Death, Sudden, Cardiac/prevention & control ; Defibrillators, Implantable ; Drug Therapy, Combination ; Exercise Test ; Female ; Humans ; Male ; Maximum Tolerated Dose ; Single-Blind Method ; Tachycardia, Ventricular/physiopathology ; Young Adult |
| مستخلص: | Importance: Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a potentially lethal genetic arrhythmia syndrome characterized by polymorphic ventricular tachycardia with physical or emotional stress, for which current therapy with β-blockers is incompletely effective. Flecainide acetate directly suppresses sarcoplasmic reticulum calcium release-the cellular mechanism responsible for triggering ventricular arrhythmias in CPVT-but has never been assessed prospectively. Objective: To determine whether flecainide dosed to therapeutic levels and added to β-blocker therapy is superior to β-blocker therapy alone for the prevention of exercise-induced arrhythmias in CPVT. Design, Setting, and Participants: This investigator-initiated, multicenter, single-blind, placebo-controlled crossover clinical trial was conducted from December 19, 2011, through December 29, 2015, with a midtrial protocol change at 10 US sites. Patients with a clinical diagnosis of CPVT and an implantable cardioverter-defibrillator underwent a baseline exercise test while receiving maximally tolerated β-blocker therapy that was continued throughout the trial. Patients were then randomized to treatment A (flecainide or placebo) for 3 months, followed by exercise testing. After a 1-week washout period, patients crossed over to treatment B (placebo or flecainide) for 3 months, followed by exercise testing. Interventions: Patients received oral flecainide or placebo twice daily, with the dosage guided by trough serum levels. Main Outcomes and Measures: The primary end point of ventricular arrhythmias during exercise was compared between the flecainide and placebo arms. Exercise tests were scored on an ordinal scale of worst ventricular arrhythmia observed (0 indicates no ectopy; 1, isolated premature ventricular beats; 2, bigeminy; 3, couplets; and 4, nonsustained ventricular tachycardia). Results: Of 14 patients (7 males and 7 females; median age, 16 years [interquartile range, 15.0-22.5 years]) randomized, 13 completed the study. The median baseline exercise test score was 3.0 (range, 0-4), with no difference noted between the baseline and placebo (median, 2.5; range, 0-4) exercise scores. The median ventricular arrhythmia score during exercise was significantly reduced by flecainide (0 [range, 0-2] vs 2.5 [range, 0-4] for placebo; P < .01), with complete suppression observed in 11 of 13 patients (85%). Overall and serious adverse events did not differ between the flecainide and placebo arms. Conclusions and Relevance: In this randomized clinical trial of patients with CPVT, flecainide plus β-blocker significantly reduced ventricular ectopy during exercise compared with placebo plus β-blocker and β-blocker alone. Trial Registration: clinicaltrials.gov Identifier: NCT01117454. |
| References: | Circulation. 2015 Jun 23;131(25):2185-93. (PMID: 26019152) Am J Hum Genet. 2001 Dec;69(6):1378-84. (PMID: 11704930) Heart Rhythm. 2013 Apr;10(4):542-7. (PMID: 23286974) Circ Res. 2011 Jul 22;109(3):291-5. (PMID: 21680895) Heart Rhythm. 2016 Feb;13(2):609-13. (PMID: 26416620) Heart Rhythm. 2006 Dec;3(12):1486-9. (PMID: 17161793) J Am Coll Cardiol. 2011 May 31;57(22):2244-54. (PMID: 21616285) J Cardiovasc Electrophysiol. 2008 Dec;19(12):1319-21. (PMID: 18554199) Nat Med. 2009 Apr;15(4):380-3. (PMID: 19330009) Circ Res. 2011 Apr 1;108(7):871-83. (PMID: 21454795) Circ Arrhythm Electrophysiol. 2015 Jun;8(3):633-42. (PMID: 25713214) N Engl J Med. 2008 May 8;358(19):2024-9. (PMID: 18463378) Heart Rhythm. 2016 Feb;13(2):433-40. (PMID: 26432584) Heart Rhythm. 2013 Dec;10(12):1932-63. (PMID: 24011539) Circ Arrhythm Electrophysiol. 2011 Apr;4(2):128-35. (PMID: 21270101) Heart Rhythm. 2007 May;4(5):675-8. (PMID: 17467641) Circulation. 2001 Jan 16;103(2):196-200. (PMID: 11208676) Heart Rhythm. 2013 Nov;10(11):1671-5. (PMID: 23954267) Circulation. 2009 May 12;119(18):2426-34. (PMID: 19398665) Europace. 2012 Feb;14(2):175-83. (PMID: 21893508) |
| معلومات مُعتمدة: | R01 HL088635 United States HL NHLBI NIH HHS; R01 HL108173 United States HL NHLBI NIH HHS; R01 HL124935 United States HL NHLBI NIH HHS |
| سلسلة جزيئية: | ClinicalTrials.gov NCT01117454 |
| المشرفين على المادة: | 0 (Adrenergic beta-Antagonists) 0 (Anti-Arrhythmia Agents) K94FTS1806 (Flecainide) |
| SCR Disease Name: | Polymorphic catecholergic ventricular tachycardia |
| تواريخ الأحداث: | Date Created: 20170512 Date Completed: 20190603 Latest Revision: 20220410 |
| رمز التحديث: | 20240628 |
| مُعرف محوري في PubMed: | PMC5548393 |
| DOI: | 10.1001/jamacardio.2017.1320 |
| PMID: | 28492868 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 2380-6591 |
|---|---|
| DOI: | 10.1001/jamacardio.2017.1320 |