SGLT2 inhibitors improve clinical outcomes in patients with heart failure undergoing transcatheter aortic valve replacement: real world evidence from the trinetx database

Background Transcatheter aortic valve replacement (TAVR) is now the standard of care for patients with severe symptomatic aortic stenosis. Sodium-glucose cotransporter-2 (SGLT2) inhibitors have demonstrated significant benefits in patients with heart failure (HF), regardless of ejection fraction; however, their specific effects in patients undergoing TAVR with HF remain understudied, as individuals with valvular heart disease were excluded from major clinical trials assessing the efficacy and safety of SGLT2 inhibitors in HF. The Dapa-TAVI trial reported a reduction in the composite outcome of all-cause mortality or worsening HF in patients receiving SGLT2 inhibitors post-TAVR, although the observed effect size was smaller than expected (1).Given this critical evidence gap, we sought to evaluate the association between SGLT2 inhibitor use and major adverse outcomes in HF patients following TAVR using a large, multi-institutional real-world database. Methods We conducted a retrospective, propensity score-matched cohort study analyzing de-identified electronic medical records from the TriNetX federated health research network, a globally distributed platform comprising 68 healthcare organizations. Patients with nonrheumatic aortic stenosis and HF who underwent TAVR and subsequently received SGLT2 inhibitors (dapagliflozin or empagliflozin; n=660) were propensity score-matched to patients who did not receive SGLT2 inhibitors post-TAVR (n=660). Primary outcomes included acute myocardial infarction (MI), all-cause mortality, stroke, cardiac arrest, and acute kidney injury (AKI), assessed from one day post-TAVR to final follow up. Risk metrics including risk differences, risk ratios (RR), and odds ratios (OR) were calculated with corresponding 95% confidence intervals (CIs). Results Patients receiving SGLT2 inhibitors post-TAVR exhibited significantly reduced all-cause mortality compared to controls (18.9% vs. 28.6%; RR=0.661, 95% CI: 0.542-0.807, p<0.001) and reduced risk of stroke (9.5% vs. 13.0%; RR=0.733, 95% CI: 0.539-0.995, p=0.045). Acute MI (14.4% vs. 13.8%; RR=1.044, 95% CI: 0.800-1.363, p=0.752), cardiac arrest (4.2% vs. 3.8%; RR=1.120, 95% CI: 0.660-1.900, p=0.674), and AKI (32.6% vs. 27.9%; RR=1.168, 95% CI: 0.991-1.378, p=0.063) were comparable between cohorts. Kaplan-Meier analysis indicated significantly improved survival probability in the SGLT2 group. Conclusions In HF patients undergoing TAVR, post-procedural treatment with SGLT2 inhibitors is associated with significantly lower all-cause mortality and stroke risk in this large, real-world, multi-institutional cohort. These findings suggest potential benefit in incorporating SGLT2 inhibitors into the post-procedural management of these patients and support the need for larger, randomized controlled trials to confirm these observations and establish definitive treatment guidelines for this high-risk population.