Abstract 4362756: Sodium-Glucose Cotransporter-2 Inhibitors in Moderate Aortic Stenosis

Abstract

Introduction: Moderate AS is associated with an increased risk of both CV and all-cause mortality. There are currently no approved medications to slow its progression to severe AS. We assessed the effects of sodium-glucose SGLT2is in patients with moderate AS. Methods: We conducted a retrospective cohort analysis of de-identified, aggregate patient data from the nationwide TriNetX research network. Patients ≥18 years with TTE-proven native trileaflet moderate AS (AVA 1.0-1.5 cm2) (1/2018-1/2022) were identified and classified into 2 groups: 1) patients never prescribed SLGLT2i and 2) patients with SLGLT2i initiation within 3 months of index TTE. They were followed for up to 3 years. Patients with an eGFR <30 were excluded. Primary outcome was progression to severe AS (AVA < 1.0 cm2). Secondary outcomes included all-cause mortality and acute decompensated heart failure (ADHF). We conducted a tight 1:1 propensity score matching for baseline demographics, comorbidities, medications - including HF GDMT, LVEF, AVA, NT-proBNP, and HbA1c levels. Results: 486 patients prescribed an SGLT2i and 3,044 patients never prescribed an SGLT2i were included. Patients in the SGLT2i group were older (71.3 vs. 63.1), more likely to have DM (83% vs. 31%) and CKD (39.3% vs. 23%), and had higher baseline AVA (1.31 cm2 vs. 1.21 cm2; p<0.001). Both groups had similar LVEFs (58.1% vs. 59.3%; p=0.55). During follow-up, patients prescribed SGLT2i were less likely to progress to severe AS (13% vs 22.7% - unadjusted HR 0.548 [95% CI: 0.41–0.73]; p<0.0001). After multivariable adjustment, SGLT2i use was independently associated with reduced risk of progression (aHR 0.553 [95% CI: 0.42–0.73]; p<0.0001). Risk factors for progression were index-TTE AVA, male sex, older age, white race, CAD, HF, and CKD. Following PSM, 620 patients were included (310 per group; mean age 54.3; 55% female; mean AVA 1.27 cm2; mean LVEF 58%). The SGLT2i group was less likely to progress to severe AS (matched HR 0.589 [95% CI: 0.39–0.90]; p=0.013). SGLT2i use was associated with a lower risk of all-cause mortality (mHR 0.393 [95% CI: 0.27–0.58]; p<0.0001) and ADHF (mHR 0.578 [95% CI: 0.34–0.99]; p = 0.04) (Fig 1). Conclusions: SGLT2is is associated with slower progression from moderate AS to severe AS. Prospective studies are needed to confirm and strengthen these findings.