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 individ-ual studies. We aim to conduct a meta-analysis includ-ing 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 inhibi-tors. 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%) espe-cially 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 signif-icantly reduce the incidence of atrial fibrillation, and this effect is primarily seen when given as monother-apy 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). (Curr Probl Cardiol 2023;48:101582.)

Automated summary

A meta-analysis was conducted to evaluate the effects of SGLT2 inhibitors on the occurrence of atrial fibrillation (AF) and stroke. The analysis included 56 trials and found that SGLT2 inhibitors significantly reduced the incidence of AF, particularly in monotherapy and among patients with type 2 diabetes. However, these inhibitors had no significant effect on the incidence of stroke, except in patients with stage 2 chronic kidney disease (CKD) and beyond.