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Packer DL, et al. "Effect of Catheter Ablation vs Antiarrhythmic Drug Therapy on Mortality, Stroke, Bleeding, and Cardiac Arrest Among Patients With Atrial Fibrillation". JAMA. 2019. 321(13):1261-1274.
PubMedFull text

Clinical Question

In patients with atrial fibrillation (AF) requiring treatment, is catheter ablation superior to medical therapy with regard to death, disabling stroke, serious bleeding, or cardiac arrest?

Bottom Line

In patients with atrial fibrillation (AF) requiring treatment, catheter ablation was not associated with a significant reduction in death, disabling stroke, serious bleeding, or cardiac arrest when compared to medical therapy at 12 months.

Major Points

Catheter ablation is an increasingly common strategy for achieving durable rhythm control in patients with symptomatic atrial fibrillation (AF). Two landmark randomized controlled trials (CASTLE-AF and AATAC) have established the safety and efficacy of AF ablation in patients with symptomatic systolic heart failure, in which restoration of sinus rhythm is particularly desirable. In both of these trials, AF ablation (when compared to medical therapy) not only improved quality of life and functional status, but also had salutary effects on overall mortality and heart failure hospitalization. Whether AF ablation has similar benefit in the general population of AF patients requiring therapy (e.g., symptoms, rapid rates) remains unclear.

The 2019 Catheter Ablation vs Antiarrhythmic Drug Therapy for Atrial Fibrillation (CABANA) trial randomized 2204 patients with AF to catheter ablation versus medical therapy and assessed for a primary endpoint of composite cardiovascular events. Most patients (88.4%) randomized to medical therapy received at least one rhythm control agent. At 12 months, catheter ablation did not reduce the rate of death, disabling stroke, serious bleeding, or cardiac arrest (8.0% in ablation group versus 9.2% in anti-arrhythmic group). Catheter ablation was associated with a 48% relative reduction in recurrent AF, as well as a 6.4% absolute reduction in death or CV hospitalization (driven by reduction in CV hospitalization). Notably, there was a high crossover rate (301/1096 [27.5%] randomized to medical therapy received ablation, and 102/1108 [9.2%] randomized to ablation received medical therapy), which may have resulted in dilution of any benefit with ablation on harder outcomes. This is supported by treatment-received analyses, in which patients who actually received ablation had a 23% relative reduction in the primary outcome and a 32% relative reduction in overall mortality. Importantly, however, treatment-received analyses are subject to selection bias, and should be considered hypothesis-generating only.

In summary, CABANA provides further evidence for the efficacy of AF ablation as a means of achieving rhythm control in patients with symptomatic AF. There also appears to be a modest benefit in terms of reduced CV-related hospitalizations. Furthermore, in an accompanying report of the same trial, catheter ablation did appear to improve quality of life and symptom burden to a higher degree than anti-arrhythmic therapy [1]. Critically, however, AF ablation does not appear to reduce cardiovascular events in all-comers with AF requiring therapy. Lack of benefit may have been somewhat related to high crossover rates, as suggested by treatment-received analyses in which ablation was associated with improved outcomes, but these findings are speculative. As a result, AF ablation in patients without systolic heart failure is likely to remain an elective procedure performed with the primary purpose of symptom relief in patients who have failed, are intolerant of, or decline anti-arrhythmic therapy.


As of March 2019, no guidelines have been published that reflect the results of this trial.


  • Prospective, multi-center, open-label, randomized controlled trial
  • N=2204
    • Catheter ablation (n=1108)
    • Anti-arrhythmic therapy (n=1096)
  • Setting: 126 sites in 10 countries
  • Enrollment: November 2009 to April 2016
  • Median follow-up: 48.5 months
  • Analysis: Intention-to-treat (treatment-received as secondary)
  • Primary outcome: death, disabling stroke, serious bleeding, or cardiac arrest


Inclusion Criteria

  • Age ≥ 18 years
  • Electrocardiographic evidence of one of the following in the last 6 months:
    • ≥ 2 paroxsymal AF episodes lasting ≥ 1 hour
    • ≥ 1 persistent AF episode
    • ≥ 1 longstanding persistent AF episode
  • Warrant active therapy within the past 3 months
  • Eligible for catheter ablation and ≥ 2 sequential rhythm control or rate control drugs
  • Elevated stroke risk (e.g., CHADS2-VASc score ≥ 1)

Exclusion Criteria

  • Past failure of > 2 anti-arrhythmic drugs
  • Efficacy failure of amiodarone at full dose for at least 8 week duration
  • Reversible cause of AF
  • MI, PCI, or valve/bypass surgery within 3 months
  • HOCM
  • Class IV angina or CHF
  • Other arrhythmias requiring anti-arrhythmic therapy or ablative therapy
  • Heritable arrhythmia disorder or increased risk of torsades de pointes with class I or III drugs
  • Prior catheter ablation with intention to treat AF
  • Prior surgical ablation for AF (e.g., MAZE)
  • Prior AV nodal ablation
  • Renal failure requiring dialysis
  • Contraindication to appropriate anticoagulation therapy
  • Expected survival < 1 year
  • Women of childbearing potential (unless surgically sterile)

Baseline Characteristics

From catheter ablation group

  • Demographics: age 68, male 62.7%, white 92.0%
  • Comorbidities: BMI 30, HTN 79.1%, DM 25.3%, OSA 23.6%, CAD 18.8%, heart failure 15.7%, family history of AF 11.8%, prior CVA/TIA 10.6%, thromboembolism 3.7%
  • CHF: LVEF ≤35 4.8%, NYHA I 13.9%, NYHA II/III 34.3%
  • CHADS-VASc: median 3, 0-1 18.8%, 2 24.6%, 3 27.8%, 4 16.1%, ≥5 12.7%
  • AF: time since onset 1.1 years, persistent 47.3%, paroxsymal 42.4%, longstanding persistent 10.3%, prior hospitalization for AF 40.6%, prior cardioversion 36.0%, atrial flutter 12.9%, prior ablation for atrial flutter 4.3%, ≥1 rhythm control drug 81.6%, ≥2 rhythm control drugs 18.4%, CCS class 0 9.5%, CCS class I 15.1%, CCS class II 31.8%, CCS class III 36.5%, CCS class IV 7.1%


  • Randomized 1:1 to catheter ablation versus medical therapy (88% received rhythm control agents)
  • By protocol, all ablations involved isolation of all pulmonary veins
    • Addition of ancillary ablation techniques, including linear, ganglion plexus, and electrogram-based approaches, were left to the discretion of the investigators
  • Operators participating in the trial had to have at least 100 previous ablations performed
  • Patients randomized to medical therapy attempted on rate control first, followed by medical rhythm control
  • Anticoagulation administered as per contemporaneous guidelines
  • Scheduled patient follow-up done at 3, 6, and 12 months then every 6 months thereafter
  • All events for each component of the primary endpoint were reviewed and adjudicated in a blinded fashion by an independent clinical events committee
  • To determine AF recurrence rates, patients were provided with an ECG event recorder for chronicling symptomatic events; were referred for 24-hour auto detect, full-disclosure, real-time recordings on a quarterly basis; and obtained 96-hour Holter recordings every 6 months regardless of symptoms
  • Recurrent AF defined as a 30-second episode, confirmed through blinded review by an ECG Core Laboratory Committee
  • In the analysis of long-term AF recurrence, a conventional 3-month blanking period from therapy initiation was used in both treatment groups during which arrhythmia recurrences were not counted toward the recurrent AF endpoint


Comparisons are catheter ablation versus medical therapy

Primary Outcomes

Death, disabling stroke, major bleeding, or cardiac arrest
89 (8.0%) vs. 101 (9.2%); HR 0.86 [95% CI 0.65-1.15]; p = 0.30

Secondary Outcomes

All-cause mortality
58 (5.2%) vs. 67 (6.1%); HR 0.85 [95% CI 0.60-1.21]; p = 0.38
Death or cardiovascular hospitalization
573 (51.7%) vs. 637 (58.1%); HR 0.83 [95% CI 0.74-0.93]; p = 0.001

Treatment-Received Analysis

Death, disabling stroke, major bleeding, or cardiac arrest
HR 0.67 [95% CI 0.50-0.89]; p = 0.006
All-cause mortality
HR 0.60 [95% CI 0.42-0.86]; p = 0.005
Death or cardiovascular hospitalization
HR 0.83 [95% CI 0.74-0.94]; p = 0.002

Subgroup Analysis

  • Examination of prespecified subgroups based on clinical and demographic characteristics did not identify relative variations in the treatment effect of ablation large enough to be clinically significant while also possessing sufficient precision to exclude the null effect

Adverse Events

Catheter ablation
  • Cardiac tamponade (0.8%)
  • Minor hematoma (2.3%)
  • Pseudoaneursym (1.1%)
Medical therapy
  • Thyroid disorders (1.6%)
  • Proarrhythmia (0.8%)


  • Primary outcome modified from overall mortality to death, disabling stroke, serious bleeding, or cardiac arrest mid-trial due to slow enrollment and lower than expected event rates
  • High crossover rate (301/1096 [27.5%] randomized to medical therapy received ablation, and 102/1108 [9.2%] randomized to ablation received medical therapy) may result in underestimation of the benefit of ablation
  • Treatment-received analyses are subject to selection bias and thus should be considered hypothesis-generating only


  • Authors with multiple ties to industry
  • St. Jude Medical, Biosense Webster, Medtronic, and Boston Scientific had no role in the design of the study; collection, management, and interpretation of the data; preparation, review, or approval of the manuscript; or decision to submit the manuscript for publication.

Further Reading