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Could Sodium/Glucose Co-Transporter-2 Inhibitors Have Antiarrhythmic Potential in Atrial Fibrillation? Literature Review and Future Considerations

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Abstract

The global burden of atrial fibrillation (AF) is constantly increasing, necessitating novel and effective therapeutic options. Sodium glucose co-transporter 2 (SGLT2) inhibitors have been introduced in clinical practice as glucose-lowering medications. However, they have recently gained prominence for their potential to exert substantial cardiorenal protection and are being evaluated in large clinical trials including patients with type 2 diabetes and normoglycemic adults. In this review we present up-to-date available evidence in a pathophysiology-directed manner from cell to bedside. Preclinical and clinical data regarding a conceivable antiarrhythmic effect of SGLT2 inhibitors are beginning to accumulate. Herein we comprehensively present data that explore the potential pathophysiological link between SGLT2 inhibitors and AF. With regard to clinical data, no randomized controlled trials evaluating SGLT2 inhibitors effects on AF as a pre-specified endpoint are available. However, data from randomized controlled trial post-hoc analysis as well as observational studies point to a possible beneficial effect of SGLT2 inhibitors on AF. Meta-analyses addressing this question report inconsistent results and the real magnitude of AF prevention by SGLT2 inhibition remains unclear. Still, while (i) pathophysiologic mechanisms involved in AF might be favorably affected by SGLT2 inhibitors and (ii) emerging, yet inconsistent, clinical data imply that SGLT2 inhibitor-mediated cardiorenal protection could also exert antiarrhythmic effects, the argument of whether these novel drugs will reduce AF burden is unsettled and mandates appropriately designed and adequately sized randomized controlled studies.

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  1. Dimitrios A. Vrachatis and Konstantinos A. Papathanasiou contributed equally.

Authors and Affiliations

  1. 2nd Department of Cardiology, Attikon Hospital, National and Kapodistrian University of Athens, 1 Rimini Str., Chaidari, Attiki, Athens, Greece

    Dimitrios A. Vrachatis, Konstantinos A. Papathanasiou, Sotiria G. Giotaki, Vaia Lambadiari & Spyridon G. Deftereos

  2. Clinic for Cardiology and Electrophysiology, Evangelisches Krankenhaus Hagen-Haspe, Hagen, Germany

    Konstantinos E. Iliodromitis

  3. General Hospital of Athens “G.Gennimatas”, Athens, Greece

    Charalampos Kossyvakis, Konstantinos Raisakis, Andreas Kaoukis, Dimitrios Avramides & Georgios Giannopoulos

  4. Humanitas Clinical and Research Center IRCCS, Rozzano-Milan, Italy

    Bernhard Reimers & Giulio G. Stefanini

  5. Section of Cardiovascular Medicine, Department of Internal Medicine, Yale School of Medicine, New Haven, CT, USA

    Michael Cleman & Alexandra Lansky

  6. Department of Biomedical Sciences, Humanitas University, Pieve Emanuele-Milan, Italy

    Bernhard Reimers & Giulio G. Stefanini

  7. Humanitas Research Hospital IRCCS, Rozzano-Milan, Italy

    Bernhard Reimers & Giulio G. Stefanini

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Dimitrios A. Vrachatis, Konstantinos A. Papathanasiou, Konstantinos E. Iliodromitis, Sotiria G. Giotaki, Charalampos Kossyvakis, Konstantinos Raisakis, Andreas Kaoukis, Vaia Lambadiari, Dimitrios Avramides, Bernhard Reimers, Giulio G. Stefanini, Michael Cleman, Georgios Giannopoulos, Alexandra Lansky, and Spyridon G. Deftereos declare no potential conflicts of interest that might be relevant to this work.

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Vrachatis, D.A., Papathanasiou, K.A., Iliodromitis, K.E. et al. Could Sodium/Glucose Co-Transporter-2 Inhibitors Have Antiarrhythmic Potential in Atrial Fibrillation? Literature Review and Future Considerations. Drugs 81, 1381–1395 (2021). https://doi.org/10.1007/s40265-021-01565-3

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