Association of SGLT2 Inhibitors with Mortality and Bioprosthesis Valve Failure After TAVR: A Propensity-Matched Cohort Study

Q: What is the clinical evidence from this study?

Study design: Cohort. Population: Non-rheumatic aortic stenosis (n=4594). Intervention: SGLT2 inhibitors vs. No SGLT2 inhibitors. Primary outcome: All-cause mortality (HR 0.83, 95% CI 0.71-0.97, p=0.02).

Olivier Morel; Amandine Granier; Lisa Lochon; Antonin Trimaille; Arnaud Bisson; Benjamin Marchandot; Anne Bernard; Laurent Fauchier

doi:10.3390/jcm14197001

October 3, 2025Journal of Clinical MedicineOpen Access

Association of SGLT2 Inhibitors with Mortality and Bioprosthesis Valve Failure After TAVR: A Propensity-Matched Cohort Study

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Key result

SGLT2 inhibitors linked to ~17% lower all-cause mortality after TAVR.

HR 0.83
95% CI 0.71-0.97
P=0.02
n=4,594

Figures

Why the study?

Does SGLT2 inhibitor use reduce all-cause mortality and bioprosthetic valve failure in adults with non-rheumatic aortic stenosis undergoing TAVR?

Key Points

To assess whether sodium–glucose cotransporter 2 inhibitor (SGLT2i) use is associated with improved clinical outcomes, including all-cause mortality and bioprosthetic valve failure, following transcatheter aortic valve replacement (TAVR).
Conducted a retrospective cohort study using the TriNetX global health research network in adults with non-rheumatic aortic stenosis undergoing TAVR.
Applied 1:1 propensity score matching to balance baseline characteristics between SGLT2i users and non-users (n = 2,297 per group).
SGLT2i use was associated with a significant reduction in all-cause mortality compared with matched non-users (HR: 0.83; 95% CI: 0.71–0.97; p = 0.02).
SGLT2i therapy was associated with a significantly lower risk of bioprosthetic valve failure during follow-up (HR: 0.62; 95% CI: 0.39–0.99; p = 0.04).

Study Design

Type

Cohort (n=4,594)

Multicenter

Yes

Structured PICO

Does SGLT2 inhibitor use reduce all-cause mortality and bioprosthetic valve failure in adults with non-rheumatic aortic stenosis undergoing TAVR?

P

Population

4,594 propensity-matched adults with non-rheumatic aortic stenosis who underwent transcatheter aortic valve replacement, followed for a median of 1.2 years.

E

Exposure

Sodium–glucose cotransporter 2 inhibitors (SGLT2i) therapy (typically prescribed at a fixed dose of 10 mg daily)

C

Comparator

Non-users of SGLT2 inhibitors, matched 1:1 via propensity score matching on demographics, comorbidities, medications, and laboratory tests

O

Outcome

All-cause mortality and bioprosthetic valve failure (identified using ICD-10 code T85.6, reflecting EAPCI classification stages 1-3) over a mean follow-up of 1.4 ± 1 years (median 1.2, IQR 1.8 years)hard clinical

Main Result

Hazard Ratio: 0.83 (95% CI 0.71–0.97)

Absolute Event Rate: 7.51% vs 8.57%

p-value: p=0.02

In a large propensity-matched real-world cohort of TAVR recipients, SGLT2 inhibitor use was independently associated with significant reductions in both all-cause mortality and bioprosthetic valve failure.

Limitations

Retrospective observational design precludes definitive conclusions about causality
Medication exposure based on prescription records, which may not fully reflect actual patient adherence
Lack of detailed hemodynamic and echocardiographic data to assess subclinical bioprosthetic dysfunction
Definition of bioprosthetic valve failure was based on diagnostic coding, which may lack granularity
Key procedural details such as valve type and commissural alignment were not recorded
Selection bias from predominantly high-income countries may limit generalizability
Retrospective observational design precludes definitive conclusions about causality and residual confounding cannot be excluded
Medication exposure was based on prescription records, which may not fully reflect actual patient adherence or treatment duration
Detailed hemodynamic and echocardiographic data (valve gradients, effective orifice area) were not consistently available, limiting assessment of subclinical bioprosthetic dysfunction
Definition of bioprosthetic valve failure was based on diagnostic coding, which may lack granularity and be subject to misclassification
Key procedural details such as valve type (self-expanding vs. balloon-expandable), valve asymmetry, and commissural alignment were not recorded in the database

Implication

Does not yet support routine SGLT2 inhibitor use post-TAVR; extends weak observational data and leaves open randomized confirmation.

Abstract

Background: Sodium–glucose cotransporter 2 inhibitors (SGLT2i) have shown cardioprotective effects beyond glucose control. In aortic stenosis, SGLT2 expression is upregulated in myocardium and valve tissue, contributing to inflammation, oxidative stress, thrombogenicity, and calcification. SGLT2 inhibition may counteract these mechanisms, potentially reducing bioprosthetic valve failure after transcatheter aortic valve replacement (TAVR), where the diseased native valve remains in place. Objectives: This study aimed to evaluate whether SGLT2i use is associated with improved clinical outcomes, including all-cause mortality and bioprosthetic valve failure, following TAVR. Methods: We conducted a retrospective cohort study using the TriNetX global health research network. Adults with non-rheumatic aortic stenosis who underwent TAVR were stratified by SGLT2i use. Propensity score matching (1:1) was applied to balance baseline characteristics (n = 2297 per group). Primary outcomes were all-cause mortality and bioprosthetic valve failure during follow-up. Results: Before matching, SGLT2i users had more cardiovascular comorbidities. After matching, SGLT2i use was associated with a significantly lower risk of all-cause mortality (HR: 0.83; 95% CI: 0.71–0.97; p = 0.02) and bioprosthetic valve failure (HR: 0.62; 95% CI: 0.39–0.99; p = 0.04). Conclusions: In a large real-world cohort of TAVR recipients, SGLT2i use was independently associated with reduced mortality and lower risk of bioprosthetic valve failure. These findings support a potential disease-modifying role for SGLT2 inhibitors in this high-risk population and warrant further prospective investigation.

Discussion

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Cite This Study

Morel et al. (2025) conducted a cohort in Non-rheumatic aortic stenosis (n=4,594). SGLT2 inhibitors vs. No SGLT2 inhibitors was evaluated on All-cause mortality (HR 0.83, 95% CI 0.71-0.97, p=0.02). In patients undergoing transcatheter aortic valve replacement, SGLT2 inhibitor use was associated with a significantly lower risk of all-cause mortality (HR 0.83) and bioprosthetic valve failure (HR 0.62).

synapsesocial.com/papers/69ffef2eef8139f8ff7779da https://doi.org/10.3390/jcm14197001

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Association of SGLT2 Inhibitors with Mortality and Bioprosthesis Valve Failure After TAVR: A Propensity-Matched Cohort Study

Figures

Key Points

Study Design

Structured PICO

Main Result

Limitations

Implication

Abstract

Discussion

Cite This Study

Association of SGLT2 Inhibitors with Mortality and Bioprosthesis Valve Failure After TAVR: A Propensity-Matched Cohort Study

Figures

Key Points

Study Design

Structured PICO

Main Result

Limitations

Implication

Abstract

Discussion

Cite This Study

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