Early rhythm-control therapy efficacious in men and women with AF

Early rhythm control therapy outperformed usual care in both men and women with early atrial fibrillation (AF) and cardiovascular risk factors. No significant interaction effect between treatment and sex was reported. This result is in contrast with other studies, in which rhythm control therapy displayed worse outcomes in women than in men.

Men and women with AF have shown different responses to therapies and rates of cardiovascular complications [1]. The EAST-AFNET 4 trial (NCT01288352) demonstrated significant clinical benefits of early rhythm-control therapy for the included patients with AF (46% women) [2]. In the current pre-specified analysis of this trial, Prof. Isabelle van Gelder (University Medical Center Groningen, Netherlands) assessed the interaction effect of early rhythm-control therapy and sex and investigated sex-specific differences in clinical presentation [3].

Patients with early AF (≤12 months) who were >75 years of age, had a previous transient ischemic attack or stroke, or had at least 1 relevant comorbidity were eligible for this analysis (n=2,789). These patients were randomised to early rhythm-control therapy (i.e. anti-arrhythmic drug or ablation) or usual care. The primary efficacy outcomes were a composite of cardiovascular events and nights spent in hospital. The primary safety outcome was a composite of death, stroke, and rhythm control-related serious adverse events (AEs).

At baseline, a higher percentage of women displayed sinus rhythm compared with men (58% vs 51%; P<0.001), whereas men were more frequently asymptomatic (36% vs 25%; P<0.001). In addition, chronic kidney disease (stage 3 or 4) was more common in women (15% vs 11%; P=0.001) and women had a higher mean CHA₂DS₂-VASc score at baseline than men (3.73 vs 3.02; P<0.001). In contrast, heart failure (33% vs 23%), diabetes (28% vs 21%), and severe coronary artery disease (24% vs 9.6%) were more frequently reported in men than in women (P<0.001). These results show that the clinical characteristics of men and women with AF are different.

After a median follow-up time of 5.1 years, the composite outcome of cardiovascular events favoured early rhythm-control therapy over usual care significantly in women (HR 0.72; 95% CI 0.55–0.93) and numerically in men (HR 0.83; 95% CI 0.67–1.03). The treatment effect of early rhythm-control therapy did not show a significant interaction with sex (P=0.408), demonstrating that the benefit of early rhythm-control therapy is similar in women and men. The mean nights spent in hospital per year were also similar for women (1.4 days) and men (1.3 days).

The primary safety outcome showed similar event rates for women and men on early rhythm-control therapy (15.8% vs 17.2%). Notably, after 2 years of early rhythm control therapy, women displayed numerically higher rates of sinus rhythm than men (84.6% vs 80.0%), whereas men were more frequently asymptomatic (78.2% vs 69.4%).

As discussant of this study, Prof. Barbara Casadei (University of Oxford, UK) concluded: “This study shows that when we follow the guidelines and detect patients early, we can obtain good results with anti-arrhythmic therapy. However, more work needs to be done to assess the different components of early rhythm control therapy, ablation, and antiarrhythmic drugs in men and women with AF.”

1. Westerman S & Wenger N. Curr Cardiol Rev. 2019;15(2):136–144.
2. Kirchhof P, et al. N Engl J Med 2020;383:1305–1316.
3. Van Gelder IC, et al. Sex Differences in Early Rhythm Control Therapy in Patients with Atrial Fibrillation: data from the EAST trial. Late-breaking science 2, EHRA 2022, 3–5 April, Copenhagen, Denmark.

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Posted on 1 June, 202227 March, 2024