Abstract 11127: Effectiveness of Sodium-Glucose Cotransporter-2 Inhibitors in Patients With Heart Failure With Preserved Ejection Fraction and Type 2 Diabetes

Abstract

Introduction: Limited information exists on the effectiveness of sodium-glucose cotransporter-2 inhibitors (SGLT2i) among patients with heart failure with preserved ejection fraction (HFpEF) in routine clinical care. Further, it remains uncertain if all agents in the SGLT2i class confer similar benefits in HFpEF. Methods: We compared initiators of SGLT2i versus sitagliptin, a DPP-4 inhibitor, using US Medicare data (04/2013-12/2018). Patients were required to have a diagnosis of type 2 diabetes (T2D) and HFpEF, identified using a validated prediction model. The primary outcome was a composite of all-cause mortality or worsening HF, i.e., outpatient use of intravenous diuretics or hospitalization for heart failure (HHF). Hazard ratios (HR) were estimated using Cox regression adjusting for 121 confounders. To address potential unmeasured confounding, we calibrated our results using estimates for HHF from a meta-analysis of HF RCTs of SGLT2i. Results: We included 33,475 patients with HFpEF and T2D (6,924 initiated SGLT2i and 26,551 initiated sitagliptin). Initiation of SGLT2i was associated with a lower risk of the primary composite outcome (adjusted HR 0.60; 95% CI 0.54-0.68), all-cause mortality (0.62; 0.53-0.74) and worsening HF (0.58; 0.52-0.66). We observed similar associations with the primary outcome for 3 SGLT2i agents (p-value for interaction 0.28) and across subgroups based on demographics, comorbidities, and HF treatments (Figure). Bias calibrated HR were 0.79 (0.69-92) for the primary composite outcome and 0.81 (0.63-1.03) for all-cause mortality suggesting our results cannot be fully explained by residual confounding. Conclusions: In routine US clinical practice, SGLT2i demonstrated robust clinical effectiveness in older adults with HFpEF and T2D without apparent heterogeneity across the class. Given the observational nature of the study, potential confounding and HFrEF/HFpEF misclassification cannot be entirely ruled out.