Abstract Body (Do not enter title and authors here): Introduction:
Sodium-glucose co-transporter 2 inhibitors (SGLT2i) have shown cardiovascular benefits in randomized trials, including reductions in mortality and heart failure hospitalizations. However, real-world evidence on their effectiveness across the population with valvular heart disease (VHD) remains limited.

Methods:
We analyzed two matched cohorts from a federated health research network. We identified all the population VHD (excluding those who have received valve replacement or repair, those with congenital heart disease, and those with systolic heart failure). Then we divided them into those with SGLT2i prescription (n = 107,607) and those without (n = 107,607). Propensity score matching was performed on 38 variables encompassing demographics, comorbidities, medications, and laboratory covariates. Outcomes were assessed between 30 and 365 days post-index SGLT2i prescription, and those with outcomes prior to the analysis were excluded. Risk estimates, Kaplan-Meier survival analysis, and hazard ratios (HR) with 95% confidence intervals (CI) were calculated.

Results:
SGLT2i use was associated with a significantly lower risk of all-cause mortality (2.8% vs. 5.7%; HR: 0.433, 95% CI: 0.414–0.452; p<0.001). Survival at one year was higher in the SGLT2i group (96.93% vs. 93.12%). No significant differences were observed for atrial fibrillation (4.3% vs. 3.6%; HR: 1.014, 95% CI: 0.965–1.065; p=0.586) or ED visits (7.5% vs. 6.3%; HR: 1.036, 95% CI: 0.992–1.083; p=0.111). Rates of hospital admissions (0.01% vs. 0.01%; HR: 2.638, 95% CI: 0.714–9.746; p=0.459), ICU admissions (0.09% vs. 0.10%; HR: 0.845, 95% CI: 0.640–1.117; p=0.415), and cardiogenic shock (0.20% vs. 0.21%; HR: 0.836, 95% CI: 0.693–1.009; p=0.08) were similar between groups.

Conclusion:
Among the population with VHD, SGLT2i use was associated with a 57% relative reduction in all-cause mortality. Other outcomes, including atrial fibrillation, ED visits, ICU admissions, and cardiogenic shock, showed no significant differences. These findings support the need for further research.