Key Points:
- SGLT2 inhibitors have shown potential antiarrhythmic benefits in cardiometabolic disease, but their role in low-risk AF patients is unknown.
- DARE-AF is the first randomized trial to assess dapagliflozin after catheter ablation in patients without diabetes, heart failure, or chronic kidney disease. The study was conducted in China.
- At 3 months post-ablation, dapagliflozin did not reduce atrial fibrillation (AF) burden, recurrence, or improve left atrial remodeling compared with standard care.
- These findings suggest that SGLT2i may not offer rhythm benefits in patients without structural or metabolic risk factors.
Sodium-glucose co-transporter-2 inhibitors (SGLT2i), originally developed as glucose-lowering therapies, have demonstrated cardiovascular benefits in patients with diabetes, heart failure (HF), and chronic kidney disease (CKD). Post-hoc analyses and animal models have suggested a potential antiarrhythmic effect, including a reduction in atrial fibrillation (AF) incidence. However, whether SGLT2i confers rhythm control benefits in patients without comorbid cardiometabolic disease remains unclear.
To address this question, the DARE-AF trial was conducted at Beijing Anzhen Hospital, China enrolling 200 patients with symptomatic persistent AF scheduled for their first catheter ablation. Eligible participants had preserved ejection fraction (mean EF 61.7%), no diabetes, no CKD, and no heart failure, providing a relatively low-risk cohort with structurally normal hearts. The findings were presented on November 9, 2025, at the American Heart Association Scientific Sessions in New Orleans, Louisiana, with simultaneous publication in Circulation.
Patients were randomized 1:1 to receive dapagliflozin 10 mg daily or usual care, beginning after ablation and continued for three months. The primary endpoint was AF burden, measured via 7-day patch ECG monitoring at 3 months. Secondary endpoints included recurrence of AF, changes in left atrial (LA) diameter, atrial reverse remodeling, quality of life via AFEQT scores, and safety outcomes.
At 3 months, there was no significant difference in AF burden between groups (mean burden: 7.5% in the dapagliflozin group vs. 8.1% in the control group; p=0.48). AF recurrence occurred in 29.6% of the dapagliflozin group and 28.0% of the control group (HR: 1.11, 95% CI: 0.66–1.86; p=0.69). No significant improvements were observed in LA diameter, with both groups showing modest reverse remodeling. Quality of life scores (AFEQT) were similar across arms, and there were no significant differences in adverse events.
Although dapagliflozin was well tolerated, two deaths occurred in the intervention arm (one from sudden cardiac death, one from cancer), neither considered related to study drug. These findings contrast with previous observational studies in higher-risk patients and suggest that in the absence of cardiometabolic disease, SGLT2i may not reduce AF burden after ablation. In discussing the results, the investigators noted that while SGLT2i may provide rhythm benefits in metabolically compromised or fibrotic atria, these effects are unlikely to translate to relatively healthy atrial substrates. This study was supported by the Beijing Municipal Health Commission, the National Key R&D Program of China, and the National Natural Science Foundation of China.
