Comparative Genitourinary Safety of In-class Sodium-Glucose Cotransporter-2 Inhibitors among Patients with Heart Failure with Preserved Ejection Fraction: A Cohort Study

The American Heart Association recommended sodium-glucose cotransporter-2 inhibitors (SGLT2i) for the management of heart failure with preserved ejection fraction (HFpEF). However, little is known about their real-world in-class comparative safety in patients with HFpEF. We aimed to assess the comparative safety of SGLT2i in the risk of urinary tract infection (UTI) or genital infection separately or as a composite outcome among patients with HFpEF. This cohort study using MarketScan® Commercial and Medicare supplemental databases (2012–2020) included patients aged ≥ 18 years with a diagnosis of HFpEF who initiated SGLT2i therapy. Three pairwise comparison groups were established: cohort 1, dapagliflozin versus canagliflozin; cohort 2, empagliflozin versus canagliflozin; and cohort 3, dapagliflozin versus empagliflozin. After stabilized inverse probability treatment weighting, Cox proportional hazards regression was used to compare the risk of UTI or genital infection separately or as a composite outcome in each cohort. The risk of the composite outcome did not significantly differ between canagliflozin and dapagliflozin (adjusted hazard ratio [aHR] 0.64; 95