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Canadian Journal of Cardiology

Association of Eligibility for a Sodium-Glucose Cotransporter 2 Inhibitor and Cardiovascular Events in Patients With Atrial Fibrillation

      Abstract

      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 CHA2DS2-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, Plog-rank < 0.001), cardiovascular death (3.9 vs 1.5 per 100 person-years, Plog-rank < 0.001), and hospitalization for HF (2.5 vs 1.9 per 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 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.

      Résumé

      Contexte

      Les inhibiteurs du cotransporteur sodium-glucose de type 2 (iSGLT2) permettent de réduire les symptômes d’insuffisance cardiaque (IC) dans un large éventail de cas, mais leur utilisation n’a pas été étudiée chez les patients atteints de fibrillation auriculaire (FA). Nous avons voulu examiner l’association entre l’admissibilité au traitement par les iSGLT2 et les événements cardiovasculaires chez les patients atteints de FA afin d’évaluer l’utilité potentielle de ces agents dans la prise en charge de la FA.

      Méthodologie

      Nous avons regroupé les données de deux essais contrôlés randomisés (RE-LY et ACTIVE-W) menés auprès de patients atteints de FA. Au sein des groupes sous anticoagulothérapie, les patients répondant aux critères d’inscription d’au moins un des essais contrôlés randomisés de phase III sur les iSGLT2 étaient réputés « admissibles au traitement par les iSGLT2 » et les autres « non admissibles au traitement par les iSGLT2 ». Le critère d’évaluation principal était un critère composite comprenant les hospitalisations pour cause d’IC ou les décès d’origine cardiovasculaire.

      Résultats

      Au total, 21 484 patients atteints de FA (âge moyen : 71,2 ± 8,8 ans, 36,1 % de femmes, score CHA2DS2-VASc médian = 3) ont été inclus dans notre étude. La proportion de patients atteints de FA admissibles au traitement par les iSGLT2 était de 41,2 %. Les taux de mortalité cardiovasculaire ou d’hospitalisations pour cause d’IC étaient plus élevés chez les patients admissibles au traitement par les iSGLT2 (5,8 vs 3,2 pour 100 années-personnes, plog-rank < 0,001); décès d’origine cardiovasculaire : 3,9 vs 1,5 pour 100 années-personnes, plog-rank < 0,001; hospitalisations pour cause d’IC : 2,5 vs 1,9 pour 100 années-personnes, plog-rank < 0,001. De plus, selon le modèle corrigé en fonction de l’âge et du sexe, les patients admissibles au traitement par les iSGLT2D ont été associés à un risque plus élevé de décès d’origine cardiovasculaire et d’hospitalisations pour cause d’IC (rapport des risques instantanés [RRI] : 1,97; intervalle de confiance [IC] à 95 % : 1,79-2,17; p < 0,001), de décès d’origine cardiovasculaire (RRI : 2,75; IC à 95 % : 2,41-3,13; p < 0,001) et d’hospitalisations pour cause d’IC (RRI : 1,41; IC à 95 % : 1,23-1,62; p < 0,001).

      Conclusions

      Il n’y a actuellement pas d’indication des iSGLT2 pour la plupart des cas de FA; pourtant, les patients atteints de FA demeurent exposés à un risque substantiel d’événements cardiovasculaires. Des essais randomisés s’imposent pour évaluer l’efficacité des iSGLT2 en présence de FA.

      Graphical abstract

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