The Effect of Sodium-Glucose Co-Transporter 2 Inhibitors on Stroke and Atrial Fibrillation: A Systematic Review and Meta-Analysis

The effect of Sodium-glucose cotransporter-2 (SGLT2) inhibitors on the occurrence of AF and stroke remains unclear due to underpowered individual studies. We aim to conduct a meta-analysis including all studies that have evaluated the effects of SGLT2 inhibitors on the occurrence of AF and stroke. We queried electronic databases (PubMed, Cochrane CENTRAL and ClinicalTrials.gov) for randomized controlled trials assessing the effect of SGLT2 inhibitors. Trials were selected if they reported 1 or both of the pre-specified outcomes of stroke and AF. Results were pooled using a random-effects model. Subgroup analysis was conducted to study patients with T2DM, HF, CVD and CKD. 56 trials comprising 111,773 patients were included. SGLT2 inhibitors significantly reduced the incidence of AF across all studies (RR:0.87; 95%CI, [0.76-0.99], P=0.03, I^2=0%) especially when used as monotherapy (RR:0.87; 95%CI, [0.77-0.99], P=0.04, I^2=0%) and among T2DM patients (RR:0.83; 95%CI, [0.72-0.97], P=0.02, I^2=0%). The risk of stroke was not reduced after treatment with SGLT2 inhibitors (RR:0.97; 95%CI, [0.89-1.07], P=0.56, I^2=0%) and this was consistent when given as monotherapy (RR:0.98; 95%CI, [0.89-1.07], P=0.62, I^2=0%) or combination therapy (RR:0.58; 95%CI, [0.17-1.95], P=0.38, I^2=0%). This result was consistent among the 3 subpopulations: T2DM, CVD and HF, however benefit was seen in patients with CKD (eGFR<90) (RR:0.85; 95%CI, [0.75-0.97], P=0.02, I^2=0%). SGLT2 inhibitors significantly reduce the incidence of atrial fibrillation, and this effect is primarily seen when given as monotherapy and in patients with T2DM. However, they have no significant effect on the incidence of stroke, except for in patients with Stage 2 CKD and beyond (eGFR<90).