SGLT-2 inhibitors and atrial fibrillation in the Food and Drug Administration adverse event reporting system

Abstract

Background Sodium glucose cotransporter-2 inhibitors (SGLT2i) reduce the risk of heart failure and new data show they can prevent atrial fibrillation (AF). We examined the association between SGLT2i and AF in the Food and Drug Administration adverse event reporting system (FAERS). Methods We mined the FAERS from 2014q1 to 2019q4 to compare AF reporting for SGLT-2 i versus reports for other glucose lowering medications (ATC10 class). Several exclusions were sequentially applied for: concomitant medications; diabetes, cardiovascular or renal disease indication; reports for competing adverse events (genitourinary tract infections, ketoacidosis, Fournier’s gangrene, amputation). We provide descriptive statistics and calculated proportional reporting ratios (PRR). Results There were 62,098 adverse event reports for SGLT2i and 642,031 reports for other ATC10 drugs. The reporting of AF was significantly lower with SGLT2i than with other ATC10 drugs (4.8 versus 8.7/1000; p < 0.001) with a PRR of 0.55 (0.49–0.62). Results did not change substantially after excluding reports listing insulin (PRR 0.49) or anti-arrhythmics (PRR 0.59) as suspect or concomitant drugs, excluding reports with indications for cardiovascular disease (PRR 0.49) or renal disease (PRR 0.55), and those filed for competing adverse events (PRR 0.63). Results were always statistically significant whether the diabetes indication was specified. Negative and positive controls confirmed internal validity of the database. Conclusions In a large pharmacovigilance database, AF was robustly and consistently reported more frequently for diabetes medications other than SGLT2i. This finding complements available evidence from trials supporting a protective role of SGLT2i against the occurrence of AF.

SGLT2 Inhibitors and Their Antiarrhythmic Properties

“…A recent analysis of the large FDA adverse event reporting system including >700,000 adverse events revealed a lower incidence of atrial fibrillation in diabetic patients treated with SGLT2 inhibitors if compared to other glucose-lowering drugs. This highly significant finding was also consistent after excluding reports on used antiarrhythmic drugs, renal disease and/or other cardiovascular disease, indicating a robust antiarrhythmic effect [94]. Another meta-analysis including all clinical trials that investigated SGLT2 inhibitors until December 2020 also reports a significant reduction of the incidence of atrial arrhythmias with an overall prevalence of approximately 1% of the study population [73].…”

Sodium-glucose cotransporter-2 inhibitors protect against atrial fibrillation in patients with heart failure

“…(21). In a recent study of pharmacovigilance databases, AF was reported more frequently in patients taking diabetic drugs compared to patients taking SGLT2 inhibitors (22). In view of these conflicting results, more real-world data are required to verify the protective effect of SGLT-2 inhibitors against AF and the clinical feasibility of SGLT-2 inhibitors warrants further investigation.…”

Atrial Fibrillation: Pathogenesis, Predisposing Factors, and Genetics

“…These are the most widely used drugs for AF and have to be considered for patients with a history of heart failure [ 108 , 109 ]. The novel SGLT-2 inhibitors reveal beneficial effects in systolic heart failure included improved cardiac energy metabolism, the prevention of inflammation, oxidative stress, adverse cardiac remodelling, less LA enlargement, fibrosis, atrial mitochondrial dysfunction, inflammation, and AF inducibility [ 110 ].…”