SGLT2 inhibitors in patients undergoing transcatheter aortic valve implantation: a systematic review and meta-analysis
L Spadafora, M Bernardi, S SciarrettaAbstract
Background
Transcatheter aortic valve implantation (TAVI) and sodium–glucose cotransporter-2 inhibitors (SGLT2i) represent two major recent advances in cardiovascular medicine. While SGLT2 inhibitors have shown robust cardioprotective effects across a wide range of cardiovascular conditions, their role in the post-TAVI setting has not been systematically established.
Purpose
To evaluate whether treatment with SGLT2 inhibitors, compared with standard of care or no SGLT2i therapy, is associated with improved clinical outcomes in patients undergoing TAVI.
Methods
A systematic review and meta-analysis were conducted according to a prespecified protocol registered in PROSPERO. Major electronic databases were searched from inception through December 2025 for randomized and observational studies evaluating SGLT2 inhibitor use after TAVI. The primary outcome was all-cause mortality. Secondary outcomes included Heart Failure (HF) events and HF hospitalization.
Results
Four studies (one randomized controlled trial and three observational studies), including a total of 12,171 patients, met the inclusion criteria. The overall mean age of the study population was approximately 76.5 years, 61% of patients were men, and about 65% had diabetes. In the pooled random-effects analysis (Figure 1) including both randomized and observational evidence, SGLT2 inhibitor therapy was associated with a 23% relative reduction in all-cause mortality (HR 0.77, 95% CI 0.68–0.88; p < 0.001; I² = 14.9%). When the analysis was restricted to observational studies only, the association between SGLT2 inhibitor use and reduced all-cause mortality remained consistent (HR 0.76, 95% CI 0.65–0.88; p < 0.001; I² = 31.4%). In a sensitivity analysis excluding one of the two large real-world cohorts, the mortality benefit associated with SGLT2 inhibitor therapy was preserved, with a pooled hazard ratio of 0.72 (95% CI 0.62–0.84; p < 0.001; I² = 0%). HF outcomes, defined according to study-specific criteria including HF hospitalization or incident HF, showed greater variability. In a pooled analysis based on risk ratios, SGLT2 inhibitor use was associated with a lower risk of HF events; however, the association did not reach statistical significance (RR 0.76, 95% CI 0.49–1.16; p = 0.20; I² = 78.4%). In a supportive analysis restricted to studies reporting HF hospitalization only, SGLT2 inhibitor therapy was associated with a lower risk of HF hospitalization, with a consistent direction of effect across studies.
Conclusions
In patients undergoing TAVI, treatment with SGLT2 inhibitors is associated with a significant reduction in all-cause mortality. Although HF outcomes were heterogeneous, the overall direction of effect favoured SGLT2 inhibitor therapy. These findings support a potential role for SGLT2 inhibitors as adjunctive therapy after TAVI and highlight the need for further randomized trials in this setting.Figure 1For image description, please refer to the figure legend and surrounding text.