The EAST-AFNET 4 trial, conducted across 11 European countries, evaluated whether initiating rhythm control therapy early in the course of AF could reduce major cardiovascular complications. Participants included individuals diagnosed with AF within the previous year who also had underlying cardiovascular conditions. In this prespecified secondary analysis, the investigators assessed whether body mass index (BMI) and diabetes status influenced the outcomes of early rhythm control compared to usual care.
The trial enrolled 1,086 participants with obesity (BMI ≥30) and 1,690 without obesity (BMI <30). The average age across all participants was 70 years, with nearly 47% being women.
The following were the key findings of the study:
- Patients with obesity were younger on average and had a higher frequency of nonparoxysmal atrial fibrillation patterns compared to non-obese patients.
- Obesity did not affect the impact of early rhythm control therapy, with similar benefits seen in both groups (BMI <30: 0.84; BMI ≥30: 0.69).
- Among the 694 patients with diabetes, they were slightly younger and had higher CHA₂DS₂-VASc scores, indicating an increased baseline cardiovascular risk.
- Diabetes did not alter the effectiveness of early rhythm control therapy, with hazard ratios being nearly identical for patients with and without diabetes (HR 0.77 vs HR 0.78).
- Safety outcomes were comparable, as adverse event rates were consistent between diabetic and non-diabetic patients.
- The primary composite outcome of cardiovascular death, stroke, hospitalization due to heart failure, or acute coronary syndrome showed consistent reduction with early rhythm control therapy, regardless of obesity or diabetes status.
According to the authors, these findings provide reassurance that early rhythm control strategies can be safely and effectively applied across a broad patient population, including those with metabolic risk factors such as high BMI and diabetes. This is particularly significant given the rising prevalence of both conditions worldwide and their known association with AF and adverse cardiovascular outcomes.
"The results emphasize the potential of early rhythm control as a standard approach for managing newly diagnosed AF, supporting its use even in patients with complex metabolic profiles. By demonstrating consistent benefits across different subgroups, the study strengthens the evidence base for adopting early rhythm control strategies in routine clinical practice for patients with AF and coexisting cardiovascular disease,' the authors concluded.
Reference:
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. Published online July 30, 2025. doi:10.1001/jamacardio.2025.2374
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