Antiarrhythmic drug therapy and cardiac mortality in atrial fibrillation. The Stroke Prevention in Atrial Fibrillation Investigators

University of Missouri, Columbia.

BACKGROUND AND OBJECTIVES. The relation between cardiac mortality and antiarrhythmic drug administration has not been fully determined. This relation was analyzed in 1,330 patients enrolled in the Stroke Prevention in Atrial Fibrillation Study, a randomized clinical trial comparing warfarin, aspirin and placebo for the prevention of ischemic stroke or systemic embolism in patients with nonvalvular atrial fibrillation. METHODS. Patients who received antiarrhythmic drug therapy for atrial fibrillation in this study were compared with patients not receiving antiarrhythmic agents. The relative risk of cardiac mortality, including arrhythmic death, in patients receiving antiarrhythmic drug therapy was determined and adjusted for other cardiac risk factors. RESULTS. In patients receiving antiarrhythmic drug therapy, cardiac mortality was increased 2.5-fold (p = 0.006, 95% confidence interval [CI] 1.3 to 4.9) and arrhythmic death was increased 2.6-fold (p = 0.02, 95% CI 1.2 to 5.6). Among patients with a history of congestive heart failure, those given antiarrhythmic medications had a relative risk of cardiac death of 4.7 (p less than 0.001, 95% CI 1.9 to 11.6) compared with that of patients not so treated; the relative risk of arrhythmic death in the treated group was 3.7 (p = 0.01, 95% CI 1.3 to 10.4). Patients without a history of congestive heart failure had no increased risk of cardiac mortality (relative risk 0.70, 95% CI 0.2 to 3.1) during antiarrhythmic drug therapy. After exclusion of 23 patients with documented ventricular arrhythmias and adjustment for other variables predictive of cardiac death, patients receiving antiarrhythmic drugs were not at increased risk of cardiac death or arrhythmic death. However, in patients with a history of heart failure who received antiarrhythmic drug therapy, the relative risk of cardiac death was 3.3 (p = 0.05, 95% CI 0.99 to 11.1) and that of arrhythmic death was 5.8 (p = 0.009, 95% CI 1.5 to 21.7) compared with the risk in patients not taking antiarrhythmic medications. CONCLUSIONS. Although antiarrhythmic drug therapy was not randomly determined in this trial, the data suggest that in patients with atrial fibrillation and a history of congestive heart failure, the risk of such therapy may outweigh the potential benefit of maintaining sinus rhythm.

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				R. Ricci, C. Pignalberil, M. Disertori, A. Capucci, L. Padeletti, G. Botto, G. Boriani, F. Miraglia, T. de Santo, and M. Santini Antitachycardia pacing therapy to treat spontaneous atrial tachyarrhythmias: the 7250 dual defibrillator Italian Registry Eur. Heart J. Suppl., November 1, 2001; 3(suppl_P): P25 - P32. [Abstract] [PDF]

				A. Capucci, G.Q. Villani, N. Marrazzo, and M. Piepoli The complementary role of drug, ablation and device in the electrical therapy of atrial fibrillation Eur. Heart J. Suppl., November 1, 2001; 3(suppl_P): P47 - P52. [Abstract] [PDF]

				B. Darpo Spectrum of drugs prolonging QT interval and the incidence of torsades de pointes Eur. Heart J. Suppl., September 1, 2001; 3(suppl_K): K70 - K80. [Abstract] [PDF]

				B. M. RuDusky and M. A. Alpert Quinidine as an Antiarrhythmic Chest, May 1, 2001; 119(5): 1617 - 1619. [Full Text] [PDF]

				D. Babuty and M. J Lab Mechanoelectric contributions to sudden cardiac death Cardiovasc Res, May 1, 2001; 50(2): 270 - 279. [Full Text] [PDF]

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				S. Singh, R. G. Zoble, L. Yellen, M. A. Brodsky, G. K. Feld, M. Berk, and C. B. Billing Jr Efficacy and Safety of Oral Dofetilide in Converting to and Maintaining Sinus Rhythm in Patients With Chronic Atrial Fibrillation or Atrial Flutter : The Symptomatic Atrial Fibrillation Investigative Research on Dofetilide (SAFIRE-D) Study Circulation, November 7, 2000; 102(19): 2385 - 2390. [Abstract] [Full Text] [PDF]

				P. Dorian, W. Jung, D. Newman, M. Paquette, K. Wood, G. M. Ayers, J. Camm, M. Akhtar, and B. Luderitz The impairment of health-related quality of life in patients with intermittent atrial fibrillation: implications for the assessment of investigational therapy J. Am. Coll. Cardiol., October 1, 2000; 36(4): 1303 - 1309. [Abstract] [Full Text] [PDF]

				J. Mathew, S. Hunsberger, J. Fleg, F. Mc Sherry, W. Williford, and S. Yusuf Incidence, Predictive Factors, and Prognostic Significance of Supraventricular Tachyarrhythmias in Congestive Heart Failure Chest, October 1, 2000; 118(4): 914 - 922. [Abstract] [Full Text] [PDF]

				D. M Roden ELECTROPHYSIOLOGY: Antiarrhythmic drugs: from mechanisms to clinical practice Heart, September 1, 2000; 84(3): 339 - 346. [Full Text] [PDF]

				C. Torp-Pedersen, M. Moller, L. Kober, and A.J. Camm Dofetilide for the treatment of atrial fibrillation in patients with congestive heart failure Eur. Heart J., August 1, 2000; 21(15): 1204 - 1206. [PDF]

				J C Hancox, K C R Patel, and J V Jones Antiarrhythmics---from cell to clinic: past, present, and future Heart, July 1, 2000; 84(1): 14 - 24. [Full Text] [PDF]

				R.J Schilling, A.H Kadish, N.S Peters, J Goldberger, and D.W. Davies Endocardial mapping of atrial fibrillation in the human right atrium using a non-contact catheter Eur. Heart J., April 1, 2000; 21(7): 550 - 564. [Abstract] [PDF]

				D. Roy, M. Talajic, P. Dorian, S. Connolly, M. J. Eisenberg, M. Green, T. Kus, J. Lambert, M. Dubuc, P. Gagne, et al. Amiodarone to Prevent Recurrence of Atrial Fibrillation N. Engl. J. Med., March 30, 2000; 342(13): 913 - 920. [Abstract] [Full Text] [PDF]

				M. A. Wood, C. Brown-Mahoney, G. N. Kay, and K. A. Ellenbogen Clinical Outcomes After Ablation and Pacing Therapy for Atrial Fibrillation : A Meta-Analysis Circulation, March 14, 2000; 101(10): 1138 - 1144. [Abstract] [Full Text] [PDF]

				G.Y.H. Lip Atrial fibrillation and mortality Eur. Heart J., November 1, 1999; 20(21): 1525 - 1527. [PDF]

				A E Tuinenburg, I C Van Gelder, M P V. Den Berg, J Brugemann, P J De Kam, and H J G M Crijns Lack of prevention of heart failure by serial electrical cardioversion in patients with persistent atrial fibrillation Heart, October 1, 1999; 82(4): 486 - 493. [Abstract] [Full Text] [PDF]

				C. Torp-Pedersen, M. Moller, P. E. Bloch-Thomsen, L. Kober, E. Sandoe, K. Egstrup, E. Agner, J. Carlsen, J. Videbak, B. Marchant, et al. Dofetilide in Patients with Congestive Heart Failure and Left Ventricular Dysfunction N. Engl. J. Med., September 16, 1999; 341(12): 857 - 865. [Abstract] [Full Text] [PDF]

				W. G. Stevenson and L. W. Stevenson Atrial Fibrillation in Heart Failure N. Engl. J. Med., September 16, 1999; 341(12): 910 - 911. [Full Text]

				R. Lee, T. Nitta, R. B. Schuessler, D. C. Johnson, J. P. Boineau, and J. L. Cox The closed heart MAZE: a nonbypass surgical technique Ann. Thorac. Surg., June 1, 1999; 67(6): 1696 - 1702. [Abstract] [Full Text] [PDF]

				P. J. Zimetbaum and M. E. Josephson The Evolving Role of Ambulatory Arrhythmia Monitoring in General Clinical Practice Ann Intern Med, May 18, 1999; 130(10): 848 - 856. [Abstract] [Full Text] [PDF]

				E. Catherwood, W. D. Fitzpatrick, M. L. Greenberg, P. T. Holzberger, D. J. Malenka, B. R. Gerling, and J. D. Birkmeyer Cost-Effectiveness of Cardioversion and Antiarrhythmic Therapy in Nonvalvular Atrial Fibrillation Ann Intern Med, April 20, 1999; 130(8): 625 - 636. [Abstract] [Full Text] [PDF]

				M. Valderrabano and B. N. Singh Review : Electrophysiologic and Antiarrhythmic Effects of Propafenone: Focus on Atrial Fibrillation Journal of Cardiovascular Pharmacology and Therapeutics, January 1, 1999; 4(3): 183 - 198. [PDF]

				S. Riva, C. Tondo, C. Carbucicchio, P. Galimberti, G. Fassini, and P. Della Bella Incidence and clinical significance of transformation of atrial fibrillation to atrial flutter in patients undergoing long-term antiarrhythmic drug treatment Europace, January 1, 1999; 1(4): 242 - 247. [Abstract] [PDF]

				R. S. Stafford, D. C. Robson, B. Misra, J. Ruskin, and D. E. Singer Rate Control and Sinus Rhythm Maintenance in Atrial Fibrillation: National Trends in Medication Use, 1980-1996 Arch Intern Med, October 26, 1998; 158(19): 2144 - 2148. [Abstract] [Full Text] [PDF]

				M. K. Chung, R. A. Schweikert, B. L. Wilkoff, M. J. Niebauer, S. L. Pinski, R. G. Trohman, G. A. Kidwell, F. J. Jaeger, V. A. Morant, D. P. Miller, et al. Is hospital admission for initiation of antiarrhythmic therapy with sotalol for atrial arrhythmias required?: yield of in-hospital monitoring and prediction of risk for significant arrhythmia complications J. Am. Coll. Cardiol., July 1, 1998; 32(1): 169 - 176. [Abstract] [Full Text] [PDF]

				E. P. Baskin and J. J. Lynch Jr. Differential Atrial versus Ventricular Activities of Class III Potassium Channel Blockers J. Pharmacol. Exp. Ther., April 1, 1998; 285(1): 135 - 142. [Abstract] [Full Text]

				S. Nattel Experimental evidence for proarrhythmic mechanisms of antiarrhythmic drugs Cardiovasc Res, March 1, 1998; 37(3): 567 - 577. [Abstract] [Full Text] [PDF]