Effect of Catheter Ablation vs Antiarrhythmic Drug Therapy on Mortality, Stroke, Bleeding, and Cardiac Arrest among Patients with Atrial Fibrillation: The CABANA Randomized Clinical Trial

Douglas L Packer, Daniel B. Mark, Richard A. Robb, Kristi H. Monahan, Tristram D. Bahnson, Jeanne E. Poole, Peter Noseworthy, Yves D. Rosenberg, Neal Jeffries, L. Brent Mitchell, Greg C. Flaker, Evgeny Pokushalov, Alexander Romanov, T. Jared Bunch, Georg Noelker, Andrey Ardashev, Amiran Revishvili, David J. Wilber, Riccardo Cappato, Karl Heinz KuckGerhard Hindricks, D. Wyn Davies, Peter R. Kowey, Gerald V. Naccarelli, James A. Reiffel, Jonathan P. Piccini, Adam P. Silverstein, Hussein R. Al-Khalidi, Kerry L. Lee

Research output: Contribution to journalArticle

57 Citations (Scopus)

Abstract

Importance: Catheter ablation is effective in restoring sinus rhythm in atrial fibrillation (AF), but its effects on long-term mortality and stroke risk are uncertain. Objective: To determine whether catheter ablation is more effective than conventional medical therapy for improving outcomes in AF. Design, Setting, and Participants: The Catheter Ablation vs Antiarrhythmic Drug Therapy for Atrial Fibrillation trial is an investigator-initiated, open-label, multicenter, randomized trial involving 126 centers in 10 countries. A total of 2204 symptomatic patients with AF aged 65 years and older or younger than 65 years with 1 or more risk factors for stroke were enrolled from November 2009 to April 2016, with follow-up through December 31, 2017. Interventions: The catheter ablation group (n = 1108) underwent pulmonary vein isolation, with additional ablative procedures at the discretion of site investigators. The drug therapy group (n = 1096) received standard rhythm and/or rate control drugs guided by contemporaneous guidelines. Main Outcomes and Measures: The primary end point was a composite of death, disabling stroke, serious bleeding, or cardiac arrest. Among 13 prespecified secondary end points, 3 are included in this report: all-cause mortality; total mortality or cardiovascular hospitalization; and AF recurrence. Results: Of the 2204 patients randomized (median age, 68 years; 37.2% female; 42.9% had paroxysmal AF and 57.1% had persistent AF), 89.3% completed the trial. Of the patients assigned to catheter ablation, 1006 (90.8%) underwent the procedure. Of the patients assigned to drug therapy, 301 (27.5%) ultimately received catheter ablation. In the intention-to-treat analysis, over a median follow-up of 48.5 months, the primary end point occurred in 8.0% (n = 89) of patients in the ablation group vs 9.2% (n = 101) of patients in the drug therapy group (hazard ratio [HR], 0.86 [95% CI, 0.65-1.15]; P =.30). Among the secondary end points, outcomes in the ablation group vs the drug therapy group, respectively, were 5.2% vs 6.1% for all-cause mortality (HR, 0.85 [95% CI, 0.60-1.21]; P =.38), 51.7% vs 58.1% for death or cardiovascular hospitalization (HR, 0.83 [95% CI, 0.74-0.93]; P =.001), and 49.9% vs 69.5% for AF recurrence (HR, 0.52 [95% CI, 0.45-0.60]; P <.001). Conclusions and Relevance: Among patients with AF, the strategy of catheter ablation, compared with medical therapy, did not significantly reduce the primary composite end point of death, disabling stroke, serious bleeding, or cardiac arrest. However, the estimated treatment effect of catheter ablation was affected by lower-than-expected event rates and treatment crossovers, which should be considered in interpreting the results of the trial.

Original languageEnglish (US)
Pages (from-to)1261-1274
Number of pages14
JournalJAMA - Journal of the American Medical Association
Volume321
Issue number13
DOIs
StatePublished - Apr 2 2019

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Catheter Ablation
Anti-Arrhythmia Agents
Heart Arrest
Atrial Fibrillation
Randomized Controlled Trials
Stroke
Hemorrhage
Drug Therapy
Mortality
Hospitalization
Research Personnel
Recurrence
Intention to Treat Analysis
Pulmonary Veins
Drug and Narcotic Control
Therapeutics
Multicenter Studies
Outcome Assessment (Health Care)
Guidelines

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Effect of Catheter Ablation vs Antiarrhythmic Drug Therapy on Mortality, Stroke, Bleeding, and Cardiac Arrest among Patients with Atrial Fibrillation : The CABANA Randomized Clinical Trial. / Packer, Douglas L; Mark, Daniel B.; Robb, Richard A.; Monahan, Kristi H.; Bahnson, Tristram D.; Poole, Jeanne E.; Noseworthy, Peter; Rosenberg, Yves D.; Jeffries, Neal; Mitchell, L. Brent; Flaker, Greg C.; Pokushalov, Evgeny; Romanov, Alexander; Bunch, T. Jared; Noelker, Georg; Ardashev, Andrey; Revishvili, Amiran; Wilber, David J.; Cappato, Riccardo; Kuck, Karl Heinz; Hindricks, Gerhard; Davies, D. Wyn; Kowey, Peter R.; Naccarelli, Gerald V.; Reiffel, James A.; Piccini, Jonathan P.; Silverstein, Adam P.; Al-Khalidi, Hussein R.; Lee, Kerry L.

In: JAMA - Journal of the American Medical Association, Vol. 321, No. 13, 02.04.2019, p. 1261-1274.

Research output: Contribution to journalArticle

Packer, DL, Mark, DB, Robb, RA, Monahan, KH, Bahnson, TD, Poole, JE, Noseworthy, P, Rosenberg, YD, Jeffries, N, Mitchell, LB, Flaker, GC, Pokushalov, E, Romanov, A, Bunch, TJ, Noelker, G, Ardashev, A, Revishvili, A, Wilber, DJ, Cappato, R, Kuck, KH, Hindricks, G, Davies, DW, Kowey, PR, Naccarelli, GV, Reiffel, JA, Piccini, JP, Silverstein, AP, Al-Khalidi, HR & Lee, KL 2019, 'Effect of Catheter Ablation vs Antiarrhythmic Drug Therapy on Mortality, Stroke, Bleeding, and Cardiac Arrest among Patients with Atrial Fibrillation: The CABANA Randomized Clinical Trial', JAMA - Journal of the American Medical Association, vol. 321, no. 13, pp. 1261-1274. https://doi.org/10.1001/jama.2019.0693
Packer, Douglas L ; Mark, Daniel B. ; Robb, Richard A. ; Monahan, Kristi H. ; Bahnson, Tristram D. ; Poole, Jeanne E. ; Noseworthy, Peter ; Rosenberg, Yves D. ; Jeffries, Neal ; Mitchell, L. Brent ; Flaker, Greg C. ; Pokushalov, Evgeny ; Romanov, Alexander ; Bunch, T. Jared ; Noelker, Georg ; Ardashev, Andrey ; Revishvili, Amiran ; Wilber, David J. ; Cappato, Riccardo ; Kuck, Karl Heinz ; Hindricks, Gerhard ; Davies, D. Wyn ; Kowey, Peter R. ; Naccarelli, Gerald V. ; Reiffel, James A. ; Piccini, Jonathan P. ; Silverstein, Adam P. ; Al-Khalidi, Hussein R. ; Lee, Kerry L. / Effect of Catheter Ablation vs Antiarrhythmic Drug Therapy on Mortality, Stroke, Bleeding, and Cardiac Arrest among Patients with Atrial Fibrillation : The CABANA Randomized Clinical Trial. In: JAMA - Journal of the American Medical Association. 2019 ; Vol. 321, No. 13. pp. 1261-1274.
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abstract = "Importance: Catheter ablation is effective in restoring sinus rhythm in atrial fibrillation (AF), but its effects on long-term mortality and stroke risk are uncertain. Objective: To determine whether catheter ablation is more effective than conventional medical therapy for improving outcomes in AF. Design, Setting, and Participants: The Catheter Ablation vs Antiarrhythmic Drug Therapy for Atrial Fibrillation trial is an investigator-initiated, open-label, multicenter, randomized trial involving 126 centers in 10 countries. A total of 2204 symptomatic patients with AF aged 65 years and older or younger than 65 years with 1 or more risk factors for stroke were enrolled from November 2009 to April 2016, with follow-up through December 31, 2017. Interventions: The catheter ablation group (n = 1108) underwent pulmonary vein isolation, with additional ablative procedures at the discretion of site investigators. The drug therapy group (n = 1096) received standard rhythm and/or rate control drugs guided by contemporaneous guidelines. Main Outcomes and Measures: The primary end point was a composite of death, disabling stroke, serious bleeding, or cardiac arrest. Among 13 prespecified secondary end points, 3 are included in this report: all-cause mortality; total mortality or cardiovascular hospitalization; and AF recurrence. Results: Of the 2204 patients randomized (median age, 68 years; 37.2{\%} female; 42.9{\%} had paroxysmal AF and 57.1{\%} had persistent AF), 89.3{\%} completed the trial. Of the patients assigned to catheter ablation, 1006 (90.8{\%}) underwent the procedure. Of the patients assigned to drug therapy, 301 (27.5{\%}) ultimately received catheter ablation. In the intention-to-treat analysis, over a median follow-up of 48.5 months, the primary end point occurred in 8.0{\%} (n = 89) of patients in the ablation group vs 9.2{\%} (n = 101) of patients in the drug therapy group (hazard ratio [HR], 0.86 [95{\%} CI, 0.65-1.15]; P =.30). Among the secondary end points, outcomes in the ablation group vs the drug therapy group, respectively, were 5.2{\%} vs 6.1{\%} for all-cause mortality (HR, 0.85 [95{\%} CI, 0.60-1.21]; P =.38), 51.7{\%} vs 58.1{\%} for death or cardiovascular hospitalization (HR, 0.83 [95{\%} CI, 0.74-0.93]; P =.001), and 49.9{\%} vs 69.5{\%} for AF recurrence (HR, 0.52 [95{\%} CI, 0.45-0.60]; P <.001). Conclusions and Relevance: Among patients with AF, the strategy of catheter ablation, compared with medical therapy, did not significantly reduce the primary composite end point of death, disabling stroke, serious bleeding, or cardiac arrest. However, the estimated treatment effect of catheter ablation was affected by lower-than-expected event rates and treatment crossovers, which should be considered in interpreting the results of the trial.",
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TY - JOUR

T1 - Effect of Catheter Ablation vs Antiarrhythmic Drug Therapy on Mortality, Stroke, Bleeding, and Cardiac Arrest among Patients with Atrial Fibrillation

T2 - The CABANA Randomized Clinical Trial

AU - Packer, Douglas L

AU - Mark, Daniel B.

AU - Robb, Richard A.

AU - Monahan, Kristi H.

AU - Bahnson, Tristram D.

AU - Poole, Jeanne E.

AU - Noseworthy, Peter

AU - Rosenberg, Yves D.

AU - Jeffries, Neal

AU - Mitchell, L. Brent

AU - Flaker, Greg C.

AU - Pokushalov, Evgeny

AU - Romanov, Alexander

AU - Bunch, T. Jared

AU - Noelker, Georg

AU - Ardashev, Andrey

AU - Revishvili, Amiran

AU - Wilber, David J.

AU - Cappato, Riccardo

AU - Kuck, Karl Heinz

AU - Hindricks, Gerhard

AU - Davies, D. Wyn

AU - Kowey, Peter R.

AU - Naccarelli, Gerald V.

AU - Reiffel, James A.

AU - Piccini, Jonathan P.

AU - Silverstein, Adam P.

AU - Al-Khalidi, Hussein R.

AU - Lee, Kerry L.

PY - 2019/4/2

Y1 - 2019/4/2

N2 - Importance: Catheter ablation is effective in restoring sinus rhythm in atrial fibrillation (AF), but its effects on long-term mortality and stroke risk are uncertain. Objective: To determine whether catheter ablation is more effective than conventional medical therapy for improving outcomes in AF. Design, Setting, and Participants: The Catheter Ablation vs Antiarrhythmic Drug Therapy for Atrial Fibrillation trial is an investigator-initiated, open-label, multicenter, randomized trial involving 126 centers in 10 countries. A total of 2204 symptomatic patients with AF aged 65 years and older or younger than 65 years with 1 or more risk factors for stroke were enrolled from November 2009 to April 2016, with follow-up through December 31, 2017. Interventions: The catheter ablation group (n = 1108) underwent pulmonary vein isolation, with additional ablative procedures at the discretion of site investigators. The drug therapy group (n = 1096) received standard rhythm and/or rate control drugs guided by contemporaneous guidelines. Main Outcomes and Measures: The primary end point was a composite of death, disabling stroke, serious bleeding, or cardiac arrest. Among 13 prespecified secondary end points, 3 are included in this report: all-cause mortality; total mortality or cardiovascular hospitalization; and AF recurrence. Results: Of the 2204 patients randomized (median age, 68 years; 37.2% female; 42.9% had paroxysmal AF and 57.1% had persistent AF), 89.3% completed the trial. Of the patients assigned to catheter ablation, 1006 (90.8%) underwent the procedure. Of the patients assigned to drug therapy, 301 (27.5%) ultimately received catheter ablation. In the intention-to-treat analysis, over a median follow-up of 48.5 months, the primary end point occurred in 8.0% (n = 89) of patients in the ablation group vs 9.2% (n = 101) of patients in the drug therapy group (hazard ratio [HR], 0.86 [95% CI, 0.65-1.15]; P =.30). Among the secondary end points, outcomes in the ablation group vs the drug therapy group, respectively, were 5.2% vs 6.1% for all-cause mortality (HR, 0.85 [95% CI, 0.60-1.21]; P =.38), 51.7% vs 58.1% for death or cardiovascular hospitalization (HR, 0.83 [95% CI, 0.74-0.93]; P =.001), and 49.9% vs 69.5% for AF recurrence (HR, 0.52 [95% CI, 0.45-0.60]; P <.001). Conclusions and Relevance: Among patients with AF, the strategy of catheter ablation, compared with medical therapy, did not significantly reduce the primary composite end point of death, disabling stroke, serious bleeding, or cardiac arrest. However, the estimated treatment effect of catheter ablation was affected by lower-than-expected event rates and treatment crossovers, which should be considered in interpreting the results of the trial.

AB - Importance: Catheter ablation is effective in restoring sinus rhythm in atrial fibrillation (AF), but its effects on long-term mortality and stroke risk are uncertain. Objective: To determine whether catheter ablation is more effective than conventional medical therapy for improving outcomes in AF. Design, Setting, and Participants: The Catheter Ablation vs Antiarrhythmic Drug Therapy for Atrial Fibrillation trial is an investigator-initiated, open-label, multicenter, randomized trial involving 126 centers in 10 countries. A total of 2204 symptomatic patients with AF aged 65 years and older or younger than 65 years with 1 or more risk factors for stroke were enrolled from November 2009 to April 2016, with follow-up through December 31, 2017. Interventions: The catheter ablation group (n = 1108) underwent pulmonary vein isolation, with additional ablative procedures at the discretion of site investigators. The drug therapy group (n = 1096) received standard rhythm and/or rate control drugs guided by contemporaneous guidelines. Main Outcomes and Measures: The primary end point was a composite of death, disabling stroke, serious bleeding, or cardiac arrest. Among 13 prespecified secondary end points, 3 are included in this report: all-cause mortality; total mortality or cardiovascular hospitalization; and AF recurrence. Results: Of the 2204 patients randomized (median age, 68 years; 37.2% female; 42.9% had paroxysmal AF and 57.1% had persistent AF), 89.3% completed the trial. Of the patients assigned to catheter ablation, 1006 (90.8%) underwent the procedure. Of the patients assigned to drug therapy, 301 (27.5%) ultimately received catheter ablation. In the intention-to-treat analysis, over a median follow-up of 48.5 months, the primary end point occurred in 8.0% (n = 89) of patients in the ablation group vs 9.2% (n = 101) of patients in the drug therapy group (hazard ratio [HR], 0.86 [95% CI, 0.65-1.15]; P =.30). Among the secondary end points, outcomes in the ablation group vs the drug therapy group, respectively, were 5.2% vs 6.1% for all-cause mortality (HR, 0.85 [95% CI, 0.60-1.21]; P =.38), 51.7% vs 58.1% for death or cardiovascular hospitalization (HR, 0.83 [95% CI, 0.74-0.93]; P =.001), and 49.9% vs 69.5% for AF recurrence (HR, 0.52 [95% CI, 0.45-0.60]; P <.001). Conclusions and Relevance: Among patients with AF, the strategy of catheter ablation, compared with medical therapy, did not significantly reduce the primary composite end point of death, disabling stroke, serious bleeding, or cardiac arrest. However, the estimated treatment effect of catheter ablation was affected by lower-than-expected event rates and treatment crossovers, which should be considered in interpreting the results of the trial.

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