A prespecified secondary analysis of the EAST-AFNET 4 trial has found that the benefits of an early rhythm control strategy for patients with recently diagnosed atrial fibrillation (AF) are maintained regardless of whether patients have obesity or diabetes.¹ These findings suggest that clinicians should not withhold this therapeutic approach based on these common metabolic comorbidities.
The original EAST-AFNET 4 trial demonstrated that early rhythm control (ERC) therapy, in addition to standard care, reduced adverse cardiovascular outcomes compared to usual care. This subanalysis aimed to determine if the effectiveness and safety of ERC were influenced by body mass index (BMI) or the presence of diabetes.
EAST-AFNET 4 was an international, investigator-initiated, randomised clinical trial involving 2,789 patients with early AF (diagnosed ≤1 year prior to enrolment) and existing cardiovascular conditions. Participants were randomised to either an ERC strategy (using anti-arrhythmic drugs, catheter ablation, or cardioversion) or usual care, where rate control was the initial approach.
This secondary analysis stratified patients by obesity (BMI ≥30) and the presence of diabetes. The primary outcome was a composite of cardiovascular death, stroke, hospitalisation for worsening heart failure, or hospitalisation for acute coronary syndrome.
The analysis included 1,086 patients with obesity and 1,690 without. Patients with obesity were younger but had a higher prevalence of nonparoxysmal AF. The study found that obesity did not significantly alter the effect of ERC on the primary outcome (hazard ratio [HR] 0.69 for BMI ≥30 vs 0.84 for BMI <30; P for interaction=.22).
Similarly, in the analysis of 694 patients with diabetes, the presence of the condition did not interact with the treatment effect of ERC. The primary outcome was reduced to a similar extent in patients with and without diabetes (HR 0.77 vs 0.78, respectively; P for interaction=.93).
Across both the obesity and diabetes subgroups, safety outcomes, including serious adverse events related to anti-arrhythmic drug therapy or AF ablation, were comparable between the ERC and usual care arms.
These findings provide important reassurance for clinicians managing the large and growing population of AF patients with metabolic comorbidities. Historically, there has been some reluctance to offer rhythm control therapy to patients with obesity or diabetes, partly due to concerns about lower efficacy and higher risk.
This analysis from EAST-AFNET 4 suggests that neither obesity nor diabetes should be considered a reason to withhold an ERC strategy in patients with recently diagnosed AF. The results support the integration of ERC into the initial management plan for these high-risk individuals, alongside comprehensive risk factor management, including weight reduction and glycaemic control.
The authors noted that the trial was conducted before the widespread availability of newer agents like GLP-1 receptor agonists. Further research is needed to assess the impact of ERC in cohorts managed with modern weight-loss and antidiabetic therapies. Ongoing trials, such as EASThigh-AFNET 11 (NCT06324188) and CABA-HFPEF (NCT05508256), will further clarify the role of early AF ablation for outcome reduction in specific patient populations.
References
1. Metzner A, Willems S, Borof K, et al. Diabetes and Obesity and Treatment Effect of Early Rhythm Control vs Usual Care in Patients With Atrial Fibrillation: A Secondary Analysis of the EAST-AFNET 4 Randomized Clinical Trial. JAMA Cardiol 2025. https://doi.org/10.1001/jamacardio.2025.2374; epub ahead of press.
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