Sodium‐Glucose Cotransporter‐2 Inhibition in Patients With Newly Diagnosed Atrial Fibrillation: A Nationwide Cohort Study

Background Sodium‐glucose cotransporter‐2 (SGLT2) inhibitors reduce incident atrial fibrillation (AF), but their association with cerebrovascular and cardiovascular outcomes after AF diagnosis remains uncertain. We evaluated these outcomes in patients with newly diagnosed AF. Methods Using Taiwan's National Health Insurance Research Database, we identified patients with newly diagnosed AF from 2013 through 2022. Regular SGLT2 inhibitor users were propensity score matched 1:10 to nonusers. The primary outcome was a composite of ischemic stroke, hemorrhagic stroke, or transient ischemic attack. Secondary outcomes were all‐cause mortality and major adverse cardiovascular events. Results Of 231 030 eligible patients, 20 911 were included in the matched analysis: 1901 users and 19 010 nonusers (mean age, 72 years; 41% women; mean CHA 2 DS 2 ‐VASc score, 3.7). Baseline SGLT2 inhibitor use was not significantly associated with the primary outcome (adjusted hazard ratio [HR], 0.90 [95% CI, 0.70–1.15]; P =0.39), all‐cause mortality (adjusted HR, 0.95 [95% CI, 0.86–1.06]; P =0.38), or major adverse cardiovascular events (adjusted HR, 0.94 [95% CI, 0.84–1.05]; P =0.24). In a time‐dependent sensitivity analysis, current SGLT2 inhibitor exposure was associated with lower all‐cause mortality (adjusted HR, 0.71 [95% CI, 0.63–0.81]; P <0.01). Conclusions Among patients with newly diagnosed AF, baseline SGLT2 inhibitor use was not significantly associated with lower risks of cerebrovascular events or major adverse cardiovascular events. The lower mortality observed in the time‐dependent analysis should be interpreted cautiously because of potential residual confounding. SGLT2 inhibitors should not be considered an alternative to guideline‐directed oral anticoagulation, which remains the cornerstone of stroke prevention in eligible patients with AF.