Abstract Body (Do not enter title and authors here): Introduction
Rheumatic heart disease (RHD) remains a significant contributor to global cardiovascular morbidity, particularly in low- and middle-income populations. Although sodium-glucose co-transporter-2 inhibitors (SGLT2i) have demonstrated broad cardiovascular and renal benefits, their utility in structural heart disease, particularly RHD, has not been previously examined. This study evaluates the real-world association between SGLT2i use and clinical outcomes in patients with RHD.
Methods
We conducted a retrospective, propensity-matched cohort study using the TriNetX global research network, encompassing 103 healthcare organizations. Adults (≥18 years) diagnosed with RHD were identified using ICD-10 codes. Patients with documented exposure to SGLT2i (empagliflozin, dapagliflozin, or sotagliflozin) formed the treatment group, while those unexposed to any SGLT2i comprised the control group. Propensity score matching (1:1) was performed on demographics and comorbidities. Outcomes were assessed from 30 to 365 days after the SGLT2i prescription date; individuals with outcomes before the analysis window were excluded. Relative risk (RR), 95% confidence intervals (CI), and hazard ratios (HR) were calculated for all outcomes.
Results
After matching, 54,423 patients were included in each cohort. SGLT2i use was associated with significantly lower all-cause mortality (RR 0.571, 95% CI: 0.543–0.600, p < 0.001; HR 0.538, 95% CI: 0.511–0.566, p < 0.001). However, SGLT2i users experienced a higher incidence of acute kidney injury (AKI) (RR 1.483, 95% CI: 1.396–1.575, p < 0.001; HR 1.382, 95% CI: 1.299–1.470, p < 0.001) atrial fibrillation (RR 1.460, 95% CI: 1.365–1.562, p < 0.001; HR 1.352, 95% CI: 1.262–1.449, p < 0.001) and increased risk for emergency department visits (RR 1.380, 95% CI: 1.289–1.477, p < 0.001; HR 1.275, 95% CI: 1.188–1.367, p < 0.001).
Conclusion
In this study, SGLT2i use in patients with RHD was associated with a significant reduction in all-cause mortality but increased risk of AKI, atrial fibrillation, and ED visits. These findings suggest that while SGLT2 inhibitors may offer mortality benefit in RHD, they may carry unique risks in this structurally distinct population, highlighting the need for future studies.