Abstract Body (Do not enter title and authors here):
Background:
Aortic stenosis (AS) is the leading cause of valvular heart disease in the United States, affecting 5% of individuals over the age of 65. To date, there has been no medication known to alter the disease course of AS. There has been growing interest in the pleiotropic effects of sodium-glucose cotransporter-2 inhibitors (SGLT2i) in cardiovascular disease, including their potential in altering the natural history and outcomes in AS.

Objective:
We evaluated the impact of SGLT2i on clinical outcomes in patients with AS, with and without aortic valve replacement. Key outcomes included heart failure (HF) hospitalization, the composite of deaths and HF hospitalization, and all-cause mortality.

Methods:
A systematic review and meta-analysis was conducted per PRISMA guidelines. Studies were obtained and screened from PubMed, Ovid MedLine, and Cochrane Library databases. We included patients with AS who were initiated on an SGLT2i and followed up for a minimum of six months. Pooled analysis of outcomes was conducted using the random-effects model. Heterogeneity was assessed using the I² statistic.

Results:
Four eligible studies- one RCT and three observational studies were included. (N = 13,271). All four studies reported outcomes suitable for pooled analysis, while one large observational study (Shah. et al) also focused on AS progression. There was a 47% relative risk reduction in the composite of all-cause mortality and HF hospitalizations with SGLT2i therapy (HR 0.53; 95% CI: 0.33–0.86; p = 0.0095), with moderate heterogeneity (I²= 57.8%). There were also significantly lower odds of HF hospitalization (OR 0.35; 95% CI: 0.12–0.99; p = 0.048; I²= 72.2%). Although a favorable trend toward reduced all-cause mortality was observed, it did not reach statistical significance (HR 0.87; 95% CI: 0.69–1.10; p = 0.24; I² = 29.9%).

Conclusions:
Among patients with AS undergoing valve replacement, SGLT2i therapy was associated with a significant reduction in the composite outcome of all-cause mortality and heart failure hospitalization. The effect of SGLT2i therapy on all-cause mortality in AS, however, was not statistically significant. These findings support the role of SGLT2 inhibitors in improving HF-related outcomes in AS, while highlighting the need for larger, adequately powered studies to assess their impact on mortality.