This Article Full Text Full Text (PDF) All Versions of this Article: 109/12/1509    most recent 01.CIR.0000121736.16643.11v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Search for Related Content PubMed PubMed Citation Pubmed/NCBI databases Compound via MeSH Substance via MeSH Hazardous Substances DB AMIODARONE HYDROCHLORIDE DIGOXIN WARFARIN Related Collections Electrophysiology Arrhythmias, clinical electrophysiology, drugs Coumarins Cardiovascular Pharmacology Embolic stroke

(Circulation. 2004;109:1509-1513.)
© 2004 American Heart Association, Inc.

Clinical Investigation and Reports

Relationships Between Sinus Rhythm, Treatment, and Survival in the Atrial Fibrillation Follow-Up Investigation of Rhythm Management (AFFIRM) Study

From the University of Alabama at Birmingham.

Correspondence to Andrew E. Epstein, MD, Division of Cardiovascular Disease, Department of Medicine, The University of Alabama at Birmingham, Tinsley Harrison Tower 321L, 1530 3rd Ave South, Birmingham, AL 35294-0006. E-mail aepstein{at}uab.edu

Received July 15, 2003; de novo received September 26, 2003; revision received December 17, 2003; accepted December 23, 2003.

Background— The AFFIRM Study showed that treatment of patients with atrial fibrillation and a high risk for stroke or death with a rhythm-control strategy offered no survival advantage over a rate-control strategy in an intention-to-treat analysis. This article reports an "on-treatment" analysis of the relationship of survival to cardiac rhythm and treatment as they changed over time.

Methods and Results— Modeling techniques were used to determine the relationships among survival, baseline clinical variables, and time-dependent variables. The following baseline variables were significantly associated with an increased risk of death: increasing age, coronary artery disease, congestive heart failure, diabetes, stroke or transient ischemic attack, smoking, left ventricular dysfunction, and mitral regurgitation. Among the time-dependent variables, the presence of sinus rhythm (SR) was associated with a lower risk of death, as was warfarin use. Antiarrhythmic drugs (AADs) were associated with increased mortality only after adjustment for the presence of SR. Consistent with the original intention-to-treat analysis, AADs were no longer associated with mortality when SR was removed from the model.

Conclusions— Warfarin use improves survival. SR is either an important determinant of survival or a marker for other factors associated with survival that were not recorded, determined, or included in the survival model. Currently available AADs are not associated with improved survival, which suggests that any beneficial antiarrhythmic effects of AADs are offset by their adverse effects. If an effective method for maintaining SR with fewer adverse effects were available, it might be beneficial.

Key Words: antiarrhythmia agents • anticoagulants • arrhythmia • fibrillation

This article has been cited by other articles:

				M. Rivero-Ayerza, W. Scholte op Reimer, M. Lenzen, D. A.M.J. Theuns, L. Jordaens, M. Komajda, F. Follath, K. Swedberg, and J. G.F. Cleland New-onset atrial fibrillation is an independent predictor of in-hospital mortality in hospitalized heart failure patients: results of the EuroHeart Failure Survey Eur. Heart J., July 1, 2008; 29(13): 1618 - 1624. [Abstract] [Full Text] [PDF]

				J. B. Shea and S. F. Sears A Patient's Guide to Living With Atrial Fibrillation Circulation, May 20, 2008; 117(20): e340 - e343. [Full Text] [PDF]

				J. J. Blanc, J. Almendral, M. Brignole, M. Fatemi, K. Gjesdal, E. Gonzalez-Torrecilla, P. Kulakowski, G. Y.H. Lip, D. Shah, C. Wolpert, et al. Consensus document on antithrombotic therapy in the setting of electrophysiological procedures Europace, May 1, 2008; 10(5): 513 - 527. [Full Text] [PDF]

				S. A Lubitz, A. Fischer, and V. Fuster Catheter ablation for atrial fibrillation BMJ, April 12, 2008; 336(7648): 819 - 826. [Full Text] [PDF]

				A. Noheria, A. Kumar, J. V. Wylie Jr, and M. E. Josephson Catheter Ablation vs Antiarrhythmic Drug Therapy for Atrial Fibrillation: A Systematic Review Arch Intern Med, March 24, 2008; 168(6): 581 - 586. [Abstract] [Full Text] [PDF]

				K. Nademanee, M. C. Schwab, E. M. Kosar, M. Karwecki, M. D. Moran, N. Visessook, A. D. Michael, and T. Ngarmukos Clinical Outcomes of Catheter Substrate Ablation for High-Risk Patients With Atrial Fibrillation J. Am. Coll. Cardiol., February 26, 2008; 51(8): 843 - 849. [Abstract] [Full Text] [PDF]

				K Gjesdal, J Feyzi, and S B Olsson Digitalis: a dangerous drug in atrial fibrillation? An analysis of the SPORTIF III and V data Heart, February 1, 2008; 94(2): 191 - 196. [Abstract] [Full Text] [PDF]

				R. E. Eckart and L. M. Epstein Interventional Therapy for Atrial and Ventricular Arrhythmias Card. Surg. Adult, January 1, 2008; 3(2008): 1357 - 1374. [Full Text]

				R. K. Voeller, R. B. Schuessler, and R. J. Damiano Jr. Surgical Treatment of Atrial Fibrillation Card. Surg. Adult, January 1, 2008; 3(2008): 1375 - 1394. [Full Text]

				F. G. Cosio, E. Aliot, G. L. Botto, H. Heidbuchel, C. J. Geller, P. Kirchhof, J.-C. De Haro, R. Frank, J. P. Villacastin, J. Vijgen, et al. Delayed rhythm control of atrial fibrillation may be a cause of failure to prevent recurrences: reasons for change to active antiarrhythmic treatment at the time of the first detected episode Europace, January 1, 2008; 10(1): 21 - 27. [Abstract] [Full Text] [PDF]

				R. Nieuwlaat, L. W. Eurlings, A. Capucci, and H. J.G.M. Crijns Atrial fibrillation in the 'real world': undecided issues Eur. Heart J. Suppl., December 1, 2007; 9(suppl_I): I122 - I128. [Abstract] [Full Text] [PDF]

				H.-R. Neuberger, C. Mewis, D. J. van Veldhuisen, U. Schotten, I. C. van Gelder, M. A. Allessie, and M. Bohm Management of atrial fibrillation in patients with heart failure Eur. Heart J., November 1, 2007; 28(21): 2568 - 2577. [Abstract] [Full Text] [PDF]

				L. Friberg, N. Hammar, H. Pettersson, and M. Rosenqvist Increased mortality in paroxysmal atrial fibrillation: report from the Stockholm Cohort-Study of Atrial Fibrillation (SCAF) Eur. Heart J., October 1, 2007; 28(19): 2346 - 2353. [Abstract] [Full Text] [PDF]

				P. Jais and D. L. Packer Ablation vs. drug use for atrial fibrillation Eur. Heart J. Suppl., September 1, 2007; 9(suppl_G): G26 - G34. [Abstract] [Full Text] [PDF]

				H. Calkins, J. Brugada, D. L. Packer, R. Cappato, S.-A. Chen, H. J.G. Crijns, R. J. Damiano Jr, D. W. Davies, D. E. Haines, M. Haissaguerre, et al. HRS/EHRA/ECAS Expert Consensus Statement on Catheter and Surgical Ablation of Atrial Fibrillation: Recommendations for Personnel, Policy, Procedures and Follow-Up: A report of the Heart Rhythm Society (HRS) Task Force on Catheter and Surgical Ablation of Atrial Fibrillation Developed in partnership with the European Heart Rhythm Association (EHRA) and the European Cardiac Arrhythmia Society (ECAS); in collaboration with the American College of Cardiology (ACC), American Heart Association (AHA), and the Society of Thoracic Surgeons (STS). Endorsed and Approved by the governing bodies of the American College of Cardiology, the American Heart Association, the European Cardiac Arrhythmia Society, the European Heart Rhythm Association, the Society of Thoracic Surgeons, and the Heart Rhythm Society. Europace, June 1, 2007; 9(6): 335 - 379. [Full Text] [PDF]

				D. Gupta, M. J Earley, G. A Haywood, L. Richmond, M. Fitzgerald, P. Kojodjojo, S. C Sporton, N. S Peters, P. Broadhurst, R. J Schilling, et al. Can atrial fibrillation with a coarse electrocardiographic appearance be treated with catheter ablation of the tricuspid valve-inferior vena cava isthmus? Results of a multicentre randomised controlled trial Heart, June 1, 2007; 93(6): 688 - 693. [Abstract] [Full Text] [PDF]

				A. M. Gillinov Advances in Surgical Treatment of Atrial Fibrillation Stroke, February 1, 2007; 38(2): 618 - 623. [Abstract] [Full Text] [PDF]

				V. J. Dzau, E. M. Antman, H. R. Black, D. L. Hayes, J. E. Manson, J. Plutzky, J. J. Popma, and W. Stevenson The Cardiovascular Disease Continuum Validated: Clinical Evidence of Improved Patient Outcomes: Part II: Clinical Trial Evidence (Acute Coronary Syndromes Through Renal Disease) and Future Directions Circulation, December 19, 2006; 114(25): 2871 - 2891. [Full Text] [PDF]

				J. W.W. Wong and K.-H. Mak Impact of Maze and Concomitant Mitral Valve Surgery on Clinical Outcomes Ann. Thorac. Surg., November 1, 2006; 82(5): 1938 - 1947. [Abstract] [Full Text] [PDF]

				I. C. Van Gelder, D. G. Wyse, M. L. Chandler, H. A. Cooper, B. Olshansky, V. E. Hagens, H. J.G.M. Crijns, the RACE, and AFFIRM Investigators Does intensity of rate-control influence outcome in atrial fibrillation? An analysis of pooled data from the RACE and AFFIRM studies Europace, November 1, 2006; 8(11): 935 - 942. [Abstract] [Full Text] [PDF]

				I. C. Van Gelder and M. E.W. Hemels The progressive nature of atrial fibrillation: a rationale for early restoration and maintenance of sinus rhythm Europace, November 1, 2006; 8(11): 943 - 949. [Abstract] [Full Text] [PDF]

				D. G. Wyse Transvenous Radiofrequency Catheter Ablation for Atrial Flutter and Atrial Fibrillation: The End of the Beginning? Circulation, October 17, 2006; 114(16): 1670 - 1672. [Full Text] [PDF]

				A. Da Costa, J. Thevenin, F. Roche, C. Romeyer-Bouchard, L. Abdellaoui, M. Messier, L. Denis, E. Faure, R. Gonthier, G. Kruszynski, et al. Results From the Loire-Ardeche-Drome-Isere-Puy-de-Dome (LADIP) Trial on Atrial Flutter, a Multicentric Prospective Randomized Study Comparing Amiodarone and Radiofrequency Ablation After the First Episode of Symptomatic Atrial Flutter Circulation, October 17, 2006; 114(16): 1676 - 1681. [Abstract] [Full Text] [PDF]

				C. Pappone, G. Augello, S. Sala, F. Gugliotta, G. Vicedomini, S. Gulletta, G. Paglino, P. Mazzone, N. Sora, I. Greiss, et al. A Randomized Trial of Circumferential Pulmonary Vein Ablation Versus Antiarrhythmic Drug Therapy in Paroxysmal Atrial Fibrillation: The APAF (Ablation for Paroxysmal Atrial Fibrillation) Study J. Am. Coll. Cardiol., October 16, 2006; (2006) j.jacc.2006.08.037v1. [Abstract] [Full Text] [PDF]

				Writing Committee Members, V. Fuster, L. E. Ryden, D. S. Cannom, H. J. Crijns, A. B. Curtis, K. A. Ellenbogen, J. L. Halperin, J.-Y. Le Heuzey, G. N. Kay, et al. ACC/AHA/ESC 2006 guidelines for the management of patients with atrial fibrillation: full text: A report of the American College of Cardiology/American Heart Association Task Force on practice guidelines and the European Society of Cardiology Committee for Practice Guidelines (Writing Committee to Revise the 2001 Guidelines for the Management of Patients With Atrial Fibrillation) Developed in collaboration with the European Heart Rhythm Association and the Heart Rhythm Society Europace, September 1, 2006; 8(9): 651 - 745. [Full Text] [PDF]

				V. Fuster, L. E. Ryden, D. S. Cannom, H. J. Crijns, A. B. Curtis, K. A. Ellenbogen, J. L. Halperin, J.-Y. Le Heuzey, G. N. Kay, J. E. Lowe, et al. ACC/AHA/ESC 2006 Guidelines for the Management of Patients With Atrial Fibrillation: A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the European Society of Cardiology Committee for Practice Guidelines (Writing Committee to Revise the 2001 Guidelines for the Management of Patients With Atrial Fibrillation) Developed in Collaboration With the European Heart Rhythm Association and the Heart Rhythm Society J. Am. Coll. Cardiol., August 15, 2006; 48(4): e149 - e246. [Full Text] [PDF]

				S. N. Singh, X. C. Tang, B. N. Singh, P. Dorian, D. J. Reda, C. L. Harris, R. D. Fletcher, S. C. Sharma, J. E. Atwood, A. K. Jacobson, et al. Quality of Life and Exercise Performance in Patients in Sinus Rhythm Versus Persistent Atrial Fibrillation: A Veterans Affairs Cooperative Studies Program Substudy J. Am. Coll. Cardiol., August 15, 2006; 48(4): 721 - 730. [Abstract] [Full Text] [PDF]

				V. Fuster, L. E. Ryden, D. S. Cannom, H. J. Crijns, A. B. Curtis, K. A. Ellenbogen, J. L. Halperin, J.-Y. Le Heuzey, G. N. Kay, J. E. Lowe, et al. ACC/AHA/ESC 2006 Guidelines for the Management of Patients With Atrial Fibrillation: A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the European Society of Cardiology Committee for Practice Guidelines (Writing Committee to Revise the 2001 Guidelines for the Management of Patients With Atrial Fibrillation): Developed in Collaboration With the European Heart Rhythm Association and the Heart Rhythm Society Circulation, August 15, 2006; 114(7): e257 - e354. [Full Text] [PDF]

				G. Y H Lip and A. Tello-Montoliu Management of atrial fibrillation. Heart, August 1, 2006; 92(8): 1177 - 1182. [Full Text] [PDF]

				P. S. Chan, S. Vijan, F. Morady, and H. Oral Cost-Effectiveness of Radiofrequency Catheter Ablation for Atrial Fibrillation J. Am. Coll. Cardiol., June 20, 2006; 47(12): 2513 - 2520. [Abstract] [Full Text] [PDF]

				A. A. Elesber, A. G. Rosales, R. M. Herges, W.-K. Shen, B. S. Moon, J. F. Malouf, N. M. Ammash, V. Somers, D. O. Hodge, B. J. Gersh, et al. Relapse and mortality following cardioversion of new-onset vs. recurrent atrial fibrillation and atrial flutter in the elderly Eur. Heart J., April 1, 2006; 27(7): 854 - 860. [Abstract] [Full Text] [PDF]

				S. K Leaver and T. B L Ho Inadvertent toxic drug reaction in the management of atrial fibrillation. J R Soc Med, March 1, 2006; 99(3): 149 - 150. [Full Text] [PDF]

				M. Rienstra, I. C. Van Gelder, V. E. Hagens, N. J.G.M. Veeger, D. J. Van Veldhuisen, H. J.G.M. Crijns, and for the RACE Investigators Mending the rhythm does not improve prognosis in patients with persistent atrial fibrillation: a subanalysis of the RACE study Eur. Heart J., February 1, 2006; 27(3): 357 - 364. [Abstract] [Full Text] [PDF]

				M J Earley, D J R Abrams, A D Staniforth, S C Sporton, and R J Schilling Catheter ablation of permanent atrial fibrillation: medium term results Heart, February 1, 2006; 92(2): 233 - 238. [Abstract] [Full Text] [PDF]

				F R Quinn and A C Rankin Atrial fibrillation ablation in the real world Heart, December 1, 2005; 91(12): 1507 - 1508. [Abstract] [Full Text] [PDF]

				E. P. Gerstenfeld Does Rhythm Control Improve Functional Status in Patients With Atrial Fibrillation? J. Am. Coll. Cardiol., November 15, 2005; 46(10): 1900 - 1901. [Full Text] [PDF]

				R. A. Wilke, R. L. Berg, H. J. Vidaillet, M. D. Caldwell, J. K. Burmester, and M. A. Hillman Impact of Age, CYP2C9 Genotype and Concomitant Medication on the Rate of Rise for Prothrombin Time During the First 30 Days of Warfarin Therapy Clin. Med. Res., November 1, 2005; 3(4): 207 - 213. [Abstract] [Full Text] [PDF]

				A. Verma, A. Natale, B. J. Padanilam, E. N. Prystowsky, A. Verma, A. Natale, B. J. Padanilam, and E. N. Prystowsky Why Atrial Fibrillation Ablation Should Be Considered First-Line Therapy for Some Patients Circulation, August 23, 2005; 112(8): 1214 - 1222. [Full Text] [PDF]

				B. J. Padanilam and E. N. Prystowsky Should Ablation Be First-Line Therapy and for Whom: The Antagonist Position Circulation, August 23, 2005; 112(8): 1223 - 1231. [Full Text] [PDF]

				M. E. Goldman and L. B. Croft Atrial Fibrillation: The Ancient Conundrum Defies Simple Solution J. Am. Coll. Cardiol., June 7, 2005; 45(11): 1813 - 1814. [Full Text] [PDF]

				O. M. Wazni, N. F. Marrouche, D. O. Martin, A. Verma, M. Bhargava, W. Saliba, D. Bash, R. Schweikert, J. Brachmann, J. Gunther, et al. Radiofrequency Ablation vs Antiarrhythmic Drugs as First-line Treatment of Symptomatic Atrial Fibrillation: A Randomized Trial JAMA, June 1, 2005; 293(21): 2634 - 2640. [Abstract] [Full Text] [PDF]

				D. Newman Rate control was more cost effective than rhythm control in persistent atrial fibrillation Evid. Based Med., April 1, 2005; 10(2): 59 - 59. [Full Text] [PDF]

				S. J. Hazel, H. S. Paterson, J. R.M. Edwards, and G. J. Maddern Surgical Treatment of Atrial Fibrillation via Energy Ablation Circulation, March 1, 2005; 111(8): e103 - e106. [Full Text] [PDF]

				K. Kikuchi, A. D. McDonald, T. Sasano, and J. K. Donahue Targeted Modification of Atrial Electrophysiology by Homogeneous Transmural Atrial Gene Transfer Circulation, January 25, 2005; 111(3): 264 - 270. [Abstract] [Full Text] [PDF]

				X. Liu, F. Ouyang, H. Mavrakis, C. Ma, J. Dong, S. Ernst, D. Bänsch, M. Antz, and K.-H. Kuck Complete pulmonary vein isolation guided by three-dimensional electroanatomical mapping for the treatment of paroxysmal atrial fibrillation in patients with hypertrophic obstructive cardiomyopathy Europace, January 1, 2005; 7(5): 421 - 427. [Abstract] [Full Text] [PDF]

				L.-F. Hsu, P. Jais, P. Sanders, S. Garrigue, M. Hocini, F. Sacher, Y. Takahashi, M. Rotter, J.-L. Pasquie, C. Scavee, et al. Catheter Ablation for Atrial Fibrillation in Congestive Heart Failure N. Engl. J. Med., December 2, 2004; 351(23): 2373 - 2383. [Abstract] [Full Text] [PDF]

				W. G. Stevenson and L. W. Stevenson Atrial Fibrillation and Heart Failure -- Five More Years N. Engl. J. Med., December 2, 2004; 351(23): 2437 - 2440. [Full Text] [PDF]

				P. Zimetbaum and M. E. Josephson Is There a Role for Maintaining Sinus Rhythm in Patients with Atrial Fibrillation? Ann Intern Med, November 2, 2004; 141(9): 720 - 726. [Abstract] [Full Text] [PDF]

				T. D. Bahnson and A. O. Grant To Be or Not To Be in Normal Sinus Rhythm: What Do We Really Know? Ann Intern Med, November 2, 2004; 141(9): 727 - 729. [Full Text] [PDF]

				G. Boriani, M. Biffi, S. Mattioli, J. S. Steinberg, A. Sadaniantz, J. Kron, A. Krahn, D. M. Denny, J. Daubert, W. B. Campbell, et al. Rhythm Control and Increased Risk of Noncardiovascular Death in the Atrial Fibrillation Follow-up Investigation of Rhythm Management Trial * Response Circulation, September 14, 2004; 110(11): e307 - e308. [Full Text] [PDF]

				A. R.J. Mitchell, A. E. Epstein, and For the AFFIRM Investigators Non-Pharmacological Methods of Maintaining Sinus Rhythm * Response Circulation, August 10, 2004; 110(6): e61 - e61. [Full Text] [PDF]

				D. G. Wyse and B. J. Gersh Atrial Fibrillation: A Perspective: Thinking Inside and Outside the Box Circulation, June 29, 2004; 109(25): 3089 - 3095. [Full Text] [PDF]

				How Important Is Sinus Rhythm for Survival of Afib Patients? Journal Watch Cardiology, June 4, 2004; 2004(604): 3 - 3. [Full Text]

				I. Savelieva and A. John Camm Atrial fibrillation and heart failure: natural history and pharmacological treatment Europace, January 1, 2003; 5(s1): S5 - S19. [Abstract] [Full Text] [PDF]