Catheter ABlation vs ANtiarrhythmic Drug Therapy for Atrial Fibrillation - CABANA

Jun 27, 2022
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Author/Summarized by Author:
Dharam J. Kumbhani, MD, SM, FACC
Summary Reviewer:
Deepak L. Bhatt, MD, MPH, MBA, FACC
Summary Supplemental Reviewer:
Anthony A. Bavry, MD,MPH,FACC
Trial Sponsor:
National Institutes of Health, St Jude Medical Foundation and Corp., Biosense Webster, Inc., JnJ Inc., Medtronic Corporation, and Boston Scientific Corporation.
Date Presented:
06/21/2022
Date Published:
12/22/2021
Date Updated:
06/27/2022
Original Posted Date:
05/10/2018
References

Contribution To Literature:

Highlighted text has been updated as of June 27, 2022.

The CABANA trial showed that ablation is not superior to drug therapy for CV outcomes at 5 years among patients with new-onset or untreated AF that required therapy.

Description:

The goal of the trial was to compare the safety and efficacy of catheter ablation compared with drug therapy for the treatment of patients with new-onset or untreated atrial fibrillation (AF).

Study Design

Patients were randomized in a 1:1 fashion to either catheter ablation (n = 1,108) or drug therapy (n = 1,096). Primary ablation was performed with standard techniques (pulmonary vein isolation [PVI]/wide area circumferential ablation [WACA], ancillary ablations as needed). Drug therapy could be either for rate or rhythm control. All patients received anticoagulation.

  • Total number of enrollees: 2,204
  • Duration of follow-up: 5 years
  • Mean patient age: 67.5 years
  • Percentage female: 37%

Inclusion criteria:

  • Paroxysmal, persistent, or longstanding persistent AF patients who warrant therapy
  • ≥65 years of age
  • <65 years of age with ≥1 cerebrovascular accident (CVA)/cardiovascular (CV) risk factor
  • Eligible for ablation
  • On ≥2 rhythm or rate control drugs 

Other salient features/characteristics:

  • Cardiomyopathy: 9%
  • Chronic heart failure: 15%
  • Prior CVA/transient ischemic attack (TIA): 10%
  • Type of AF: paroxysmal: 43%, persistent 47%
  • Prior hospitalization for AF: 39%
  • Crossover: ablation to drug:  9.2%, drug to ablation: 27.5%

Principal Findings:

The primary outcome, death, disabling stroke, serious bleeding, or cardiac arrest at 5 years for ablation vs. drug therapy, was 8% vs. 9.2% (hazard ratio [HR] 0.86, 95% confidence interval [CI] 0.65-1.15, p = 0.3).

  • Death: 5.2% vs. 6.1% for ablation vs. drug therapy (p = 0.38)
  • Serious stroke: 0.3% vs. 0.6% for ablation vs. drug therapy (p = 0.19)
  • Primary endpoint based on treatment received (for ablation vs. drug therapy): 7.0% vs. 10.9% (p = 0.006); all-cause mortality: 4.4% vs. 7.5% (p = 0.005); death or CV hospitalization: 41.2% vs. 74.9% (p = 0.002)

Secondary outcomes:

  • Death or CV hospitalization: 51.7% vs. 58.1% for ablation vs. drug therapy (HR 0.83, 95% CI 0.74-0.93, p = 0.002)
  • Pericardial effusion with ablation: 3.0%; ablation-related events: 1.8%

AF recurrence for ablation vs. drug therapy at 4 years: Assessed after 90-day blanking period (n = 2,043):

  • First recurrent AF: 52.1% vs. 70.8% (HR 0.52, 95% CI 0.45-0.60, p < 0.0001); similar reduction in symptomatic AF
  • First recurrent AF/atrial flutter/atrial tachycardia: 53.8% vs. 71.9% (p < 0.0001)
  • AF burden (% of Holter monitoring time): 6.3% vs. 14.4% at 12 months; 14.7% vs. 20.8% at 5 years

Sex-based differences: On average, women (37%) were older and more likely to be White, compared with men. They were more likely to have paroxysmal AF, but had more severe AF symptoms. Complication rates were similar. Primary endpoint for women for ablation vs. drug therapy: HR 1.01, 95% CI 0.62-1.65; for men, HR 0.73, 95% CI 0.51-1.05 (p for interaction = 0.30). Risk of recurrent AF was similarly reduced in both women (HR 0.64, 95% CI 0.51-0.82) and men (HR 0.48, 95% CI 0.40-0.58).

Patients with ≥ New York Heart Association (NYHA) class II heart failure (HF) (n = 778, 35%): Ejection fraction (EF) information was available for 73%. Of these, 9.3% had EF <40%. Paroxysmal AF was present in 32%, persistent AF in 55%. In this subgroup, the primary endpoint was significantly reduced with ablation (9% vs. 12.3%; HR 0.64, 95% CI 0.41-0.99), as was mortality (6.1% vs. 9.3%, HR 0.57, 95% CI 0.33-0.96). No reductions were noted in CV mortality or HF hospitalization. AF recurrence was also reduced with ablation (37% vs. 58%; HR 0.56, 95% CI 0.42-0.74).

Age-based differences: 34.8% were age <65 years, 51.3% were 65-74 years, and 14% were ≥75 years. For these groups respectively for ablation vs. antiarrhythmic drug therapy: primary endpoint: 3.2% vs. 7.8%; 7.8% vs. 9.6%; 14.8% vs. 9% (p for interaction = 0.13); AF recurrence: 48% vs. 69%; 57% vs. 72%; 52% vs. 78% (p for interaction = 0.40). For total mortality, adjusted HR for ablation vs. antiarrhythmic drug therapy: age <65 years: 0.46 (0.21-1.0); age 65-74 years: 0.72 (0.44-1.18); age ≥75 years: 1.92 (0.88-4.17); p for interaction = 0.03.

Cost-effectiveness analysis: This was performed on US patients in the trial (n = 1,233); hospital billing data was available for 95% of these patients. These were obtained using departmental charge-to-cost conversion factors derived from each hospital’s annual Medicare Cost Report. Physician costs and office costs were assessed separately. The average cumulative 5-year within-trial costs (adjusted for variable follow-up), including costs for hospitalization, extended care, inpatient and outpatient procedures, physician fees, and medications, were higher with catheter ablation vs. drug therapy ($75,381 vs. $56,137). Similarly, lifetime costs were $151,877 vs. $136,361, difference $15,516). Under base case assumptions, the incremental cost-effectiveness ratio (ICER) for ablation compared with drug therapy was $57,893/quality-adjusted life-year (QALY) gained, with a 75% likelihood of meeting a $100,000/QALY gained willingness-to-pay threshold. If the analysis used only the difference in life-years with no quality-of-life (QOL)/utility adjustments, the ICER was $183,318/LY gained. Among patients with heart failure, the ICER for catheter ablation compared with drug therapy was $54,135/QALY gained, with an 86% likelihood of meeting a $100,000/QALY gained willingness-to-pay threshold. Without QOL/utility adjustments, the ICER was $70,907/LY gained, with a 73% likelihood of meeting a $100,000/QALY-gained threshold.

Interpretation:

The results of this important trial indicate that ablation is not superior to drug therapy for CV outcomes at 5 years among patients with new-onset or untreated AF that required therapy. There was a significant reduction in death or CV hospitalization with ablation, and on as-treated analysis, ablation demonstrated superior efficacy to drug therapy. In addition, recurrent AF and AF burden were lower with ablation compared with drug therapy alone. In the setting of a negative primary endpoint, these latter findings are considered hypothesis generating. Catheter ablation was associated with a significant reduction in recurrent AF compared with drug therapy. Similarly, among patients with NYHA class II-IV symptoms, most of whom had HF with preserved EF, there appeared to be a benefit in the primary endpoint and all-cause mortality with ablation; this is hypothesis generating as well. No clear sex-based differences were noted in overall safety or efficacy. There appeared to be an age-based interaction, with higher benefit in younger patients and none among patients ≥75 years of age. In addition, there was a potential signal for harm in this older subgroup, although this could be due to chance due to the small sample size.

The cost-effectiveness analysis suggests that AF remains an expensive condition to treat, irrespective of ablation. Under base case assumptions, catheter ablation appeared to meet current ICER benchmarks for QALYs, but not for life-years alone. The cost-effectiveness performance appeared to be higher among patients with heart failure.

A couple of caveats exist. The drug-therapy arm is very heterogeneous, and it is unclear if uniform pursuance of rhythm control in that arm would be better than the rate control arm. The included population is also somewhat unclear with respect to the patients who would most benefit with this therapy.

Finally, this trial is only single-blinded (not to intervention received). That may have driven the high crossover rates and can confound assessment of the various endpoints. Based on recent experiences from important sham-controlled trials (e.g., SYMPLICITY), these findings should prompt consideration of a sham-controlled trial to assess the true efficacy of catheter ablation in modulating CV outcomes among patients with AF.

References:

Chew DS, Li Y, Cowper PA, et al., on behalf of the CABANA Investigators. Cost-Effectiveness of Catheter Ablation Versus Antiarrhythmic Drug Therapy in Atrial Fibrillation: The CABANA Randomized Clinical Trial. Circulation 2022;Jun 21:[Epub ahead of print].

Bahnson TD, Giczewska A, Mark DB, et al. Association Between Age and Outcomes of Catheter Ablation Versus Medical Therapy for Atrial Fibrillation: Results From the CABANA Trial. Circulation 2022;135:796-804.

Packer DL, Piccini JP, Monahan KH, et al. Ablation Versus Drug Therapy for Atrial Fibrillation in Heart Failure: Results From the CABANA Trial. Circulation 2021;143:1377-90.

Russo AM, Zeitler EP, Giczewska A, et al., on behalf of the CABANA Investigators. Association Between Sex and Treatment Outcomes of Atrial Fibrillation Ablation Versus Drug Therapy: Results From the CABANA Trial. Circulation 2021;143:661-72.

Poole JE, Bahnson TD, Monahan KH, et al., on behalf of the CABANA Investigators and ECG Rhythm Core Lab. Recurrence of Atrial Fibrillation After Catheter Ablation or Antiarrhythmic Drug Therapy in the CABANA Trial. J Am Coll Cardiol 2020;75:3105-18.

Editorial Comment: Marchlinski FE, Walsh K, Guandalini GS. Reporting AF Recurrence After Catheter Ablation: The Burden Is on Us to Get it Right. J Am Coll Cardiol 2020;75:3119-21.

Presented by Dr. Jeanne E. Poole at the European Society of Cardiology Congress, Munich, Germany, August 26, 2018.

Presented by Dr. Douglas L. Packer at the Heart Rhythm Society Scientific Session, May 10, 2018, Boston, MA.

Clinical Topics: Anticoagulation Management, Arrhythmias and Clinical EP, Heart Failure and Cardiomyopathies, Pericardial Disease, Anticoagulation Management and Atrial Fibrillation, Implantable Devices, EP Basic Science, SCD/Ventricular Arrhythmias, Atrial Fibrillation/Supraventricular Arrhythmias, Acute Heart Failure

Keywords: ESC Congress, ESC18, Anti-Arrhythmia Agents, Anticoagulants, Arrhythmias, Cardiac, Atrial Fibrillation, Catheter Ablation, Costs and Cost Analysis, Drug Therapy, Heart Arrest, Heart Failure, Hemorrhage, Pericardial Effusion, Pulmonary Veins, Quality-Adjusted Life Years, Quality of Life, Stroke


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