Canadian Journal of Cardiology

Association of Eligibility for a Sodium-Glucose Co-transporter 2 Inhibitor and Cardiovascular Events in Patients with Atrial Fibrillation



      Sodium-glucose co-transporter 2 inhibitors (SGLT2i) reduce heart failure (HF) in a broad range of populations, but they have not been studied specifically in patients with atrial fibrillation (AF). We aimed to examine the association between SGLT2i-eligibility and cardiovascular events in AF patients to evaluate the potential utility of SGLT2is for AF management.


      We pooled data from two randomized controlled trials (RCT) of AF patients (RE-LY and ACTIVE-W). Among patients assigned to anticoagulation arms, those meeting the enrollment criteria from at least one of the phase 3 SGLT2i RCTs were classified as “SGLT2i-eligible” and the remainder as “SGLT2i-ineligible”. The primary outcome was the composite of HF hospitalization or cardiovascular death.


      A total of 21,484 AF patients (mean age: 71.2±8.8, 36.1% women, median CHA2DS2-VASc Score=3) were included. The proportion of AF patients eligible for an SGLT2i was 41.2%. SGLT2i-eligible patients had higher rates of cardiovascular death/hospitalization for HF (5.8 vs. 3.2/100 person-years, Plog-rank<0.001), cardiovascular death (3.9 vs. 1.5/100 person-years, Plog-rank<0.001), and hospitalization for HF (2.5 vs. 1.9/100 person-years, Plog-rank<0.001). The age- and sex-adjusted model showed that SGLT2i-eligible patients were at a higher risk of cardiovascular death/hospitalization for HF (HR 1.97, 95% CI 1.79-2.17; P<0.001), cardiovascular death (HR 2.75, 95% CI 2.41-3.13, P<0.001), and hospitalization for HF (HR 1.41, 95% CI 1.23-1.62, P<0.001) than ineligible patients.


      Most patients with AF do not currently have an indication for SGLT2is, but still have a substantial risk of cardiovascular events. Future randomized trials should evaluate the efficacy of SGLT2is in AF patients.

      Graphical abstract


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