Association Between Sex and Treatment Outcomes of Atrial Fibrillation Ablation Versus Drug Therapy: Results From the CABANA Trial

Abstract

Background: Among patients with atrial fibrillation (AF), women are less likely to receive catheter ablation and may have more complications and less durable results. Most information about sex-specific differences after ablation comes from observational data. We prespecified an examination of outcomes by sex in the 2204-patient CABANA trial (Catheter Ablation Versus Antiarrhythmic Drug Therapy for Atrial Fibrillation).

Methods: CABANA randomized patients with AF age ≥65 years or <65 years with ≥1 risk factor for stroke to a strategy of catheter ablation with pulmonary vein isolation versus drug therapy with rate/rhythm control agents. The primary composite outcome was death, disabling stroke, serious bleeding, or cardiac arrest, and key secondary outcomes included AF recurrence.

Results: CABANA randomized 819 (37%) women (ablation 413, drug 406) and 1385 men (ablation 695, drug 690). Compared with men, women were older (median age, 69 years versus 67 years for men), were more symptomatic (48% Canadian Cardiovascular Society AF Severity Class 3 or 4 versus 39% for men), had more symptomatic heart failure (42% with New York Heart Association Class ≥II versus 32% for men), and more often had a paroxysmal AF pattern at enrollment (50% versus 39% for men) (P<0.0001 for all). Women were less likely to have ancillary (nonpulmonary vein) ablation procedures performed during the index procedure (55.7% versus 62.2% in men, P=0.043), and complications from treatment were infrequent in both sexes. For the primary outcome, the hazard ratio for those who underwent ablation versus drug therapy was 1.01 (95% CI, 0.62-1.65) in women and 0.73 (95% CI, 0.51-1.05) in men (interaction P value=0.299). The risk of recurrent AF was significantly reduced in patients undergoing ablation compared with those receiving drug therapy regardless of sex, but the effect was greater in men (hazard ratio, 0.64 [95% CI, 0.51-0.82] for women versus hazard ratio, 0.48 [95% CI, 0.40-0.58] for men; interaction P value=0.060).

Conclusions: Clinically relevant treatment-related strategy differences in the primary and secondary clinical outcomes of CABANA were not seen between men and women, and there were no sex differences in adverse events. The CABANA trial results support catheter ablation as an effective treatment strategy for both women and men. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT00911508.

Keywords: ablation; atrial fibrillation; sex differences.

Figure 1.. Kaplan-Meier estimates of the incidence of the primary outcome in the ITT groups by sex.

aHR: adjusted hazard ratio.

Figure 2.. Recurrent atrial arrhythmias post-blanking in ablation versus drug ITT groups.

Freedom from first recurrence of atrial fibrillation, flutter, or atrial tachycardia following the blanking period in patients who used the study ECG event recorders (“CABANA-Box”) in (A) women and (B) men. aHR: adjusted hazard ratio

Figure 2.. Recurrent atrial arrhythmias post-blanking in ablation versus drug ITT groups.

Freedom from first recurrence of atrial fibrillation, flutter, or atrial tachycardia following the blanking period in patients who used the study ECG event recorders (“CABANA-Box”) in (A) women and (B) men. aHR: adjusted hazard ratio

Figure 3.

Atrial fibrillation burden by time, women versus men.

Figure 4.. Subgroup effects on primary CABANA composite outcome by randomized treatment strategy in women.

Prespecified subgroup comparisons were performed using multivariable Cox models including a treatment by covariable interaction term. After finding the Maximum Likelihood Estimator, p-values were generated based on the associated Wald Chi-Square test statistic. aHR: adjusted hazard ratio