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Background: Sodium-glucose cotransporter 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 patients with AF to evaluate the potential utility of SGLT2is for AF management., Methods: We pooled data from 2 randomized controlled trials (RCTs) of patients with AF (RE-LY and ACTIVE-W). Among patients assigned to anticoagulation arms, those meeting the enrollment criteria from at least 1 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., Results: A total of 21,484 patients with AF (mean age: 71.2 ± 8.8, 36.1% women, median CHA 2 DS 2 -VASc Score = 3) were included. The proportion of patients with AF eligible for SGLT2i was 41.2%. SGLT2i-eligible patients had higher rates of cardiovascular death or hospitalization for HF (5.8 vs 3.2 per 100 person-years, P log-rank < 0.001), cardiovascular death (3.9 vs 1.5 per 100 person-years, P log-rank < 0.001), and hospitalization for HF (2.5 vs 1.9 per 100 person-years, P log-rank < 0.001). The age- and sex-adjusted model showed that SGLT2i-eligible patients were at a higher risk of cardiovascular death and hospitalization for HF (hazard ratio [HR], 1.97; 95% confidence interval [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., Conclusions: Most patients with AF do not currently have indications for SGLT2is but still have substantial risk of cardiovascular events. Future randomized trials should evaluate the efficacy of SGLT2is in patients with AF., (Copyright © 2022 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.)

Background The COMPASS (Cardiovascular Outcomes for People Using Anticoagulation Strategies) trial showed that rivaroxaban plus aspirin reduced major adverse cardiovascular events (MACE) in patients with chronic coronary artery disease (CAD) and/or peripheral artery disease (PAD). We explored whether CHA 2 DS 2 -VASc or CHADS 2 scores, well-validated tools for assessing risk of thromboembolic events in atrial fibrillation, can identify vascular patients at highest risk of recurrent events who may derive greatest benefits of treatment. Methods Predictive accuracies of the CHA 2 DS 2 -VASc and CHADS 2 scores for MACE, were assessed in this analysis of the COMPASS trial. Kaplan-Meier estimates of cumulative risk were used to compare the effects of rivaroxaban plus aspirin (n = 9152) with aspirin alone (n = 9126) according to risk scores. Results High CHA 2 DS 2 -VASc (6-9) or CHADS 2 (3-6) scores were associated with over three times greater absolute risk of MACE compared with CHA 2 DS 2 -VASc score of 1-2 or CHADS 2 score of 0. The effects of rivaroxaban plus aspirin compared with aspirin alone were consistent across CHA 2 DS 2 -VASc and CHADS 2 score categories for MACE, bleeding and net clinical benefit, with greatest reduction in MACE observed in patients treated for 30 months with highest CHADS 2 score (3-6) (hazard ratio = 0.67, 95% CI: 0.53-0.86, p = 0.0012, 25 events per 1000 patients prevented). Conclusion The CHA 2 DS 2 -VASc and CHADS 2 scores can be used in patients with chronic CAD and/or PAD to identify patients who are at highest risk of MACE. Those identified at highest risk by CHADS 2 scores had greatest benefit from dual pathway inhibition with rivaroxaban plus aspirin. Clinical Trial Registration: NCT01776424., (Copyright © 2021. Published by Elsevier B.V.)