Association of Sodium–Glucose Cotransporter 2 Inhibitor Use With Outcomes in Patients Undergoing Transcatheter Aortic Valve Implantation: A Systematic Review and GRADE‐Assessed Meta‐Analysis
Key result
SGLT2 inhibitors cut all-cause mortality ~32% vs standard care after TAVI.
- RR 0.68
- 95% CI 0.48-0.97
- P=0.03
- n=6,111
Figures
Why the study?
The role of SGLT2 inhibitors in patients undergoing transcatheter aortic valve implantation remains unclear despite known cardiovascular and renal benefits in other populations.
Does SGLT2 inhibitor use reduce all-cause mortality and heart failure hospitalization in patients undergoing transcatheter aortic valve implantation?
Key Points
- To evaluate the association between sodium-glucose cotransporter 2 (SGLT2) inhibitor use and clinical outcomes in patients undergoing transcatheter aortic valve implantation.
- Systematic search of major databases through March 2026 (Embase updated through June 2026) identifying five studies (one randomized controlled trial, four observational cohorts) encompassing 6111 patients (SGLT2 inhibitors: n = 2933; control: n = 3178).
- Calculated pooled risk ratios (RRs), hazard ratios (HRs), and mean differences using random-effects models and evaluated evidence certainty using the GRADE approach.
- Primary random-effects models demonstrated that SGLT2 inhibitors were associated with lower all-cause mortality (RR 0.68, 95% CI 0.48-0.97, p = 0.03) and heart failure hospitalization (RR 0.62, 95% CI 0.42-0.90, p = 0.01).
- SGLT2 inhibitor therapy was associated with reduced major adverse cardiovascular events (RR 0.68, 95% CI 0.48-0.96, p = 0.03), though confidence intervals crossed the null in sensitivity analyses and no differences occurred at 6 or 12 months.
- Mortality reduction persisted in patients with low left ventricular ejection fraction (RR 0.56, 95% CI 0.35-0.89, p = 0.01), while no significant differences were observed for acute kidney injury or urinary tract infections.
Study Design
Type
Meta-Analysis (n=6,111)
Multicenter
Yes
Structured PICO
Does SGLT2 inhibitor use reduce all-cause mortality and heart failure hospitalization in patients undergoing transcatheter aortic valve implantation?
P
Population
6,111 adults with aortic stenosis undergoing transcatheter aortic valve implantation (TAVI), evaluated across 5 pooled studies (1 RCT and 4 observational) with up to 37.3 months of follow-up.
I
Intervention
Sodium-glucose cotransporter 2 (SGLT2) inhibitors administered before and/or after TAVI (e.g., dapagliflozin, empagliflozin)
C
Comparator
Standard care without SGLT2 inhibitor administration or non-SGLT2 inhibitor therapy
O
Outcome
All-cause mortality and heart failure (HF) hospitalizationhard clinical
Main Result
Relative Risk: 0.68 (95% CI 0.48–0.97)
Absolute Event Rate: 6.1% vs 10.2%
p-value: p=0.03
SGLT2 inhibitors may reduce all-cause mortality and heart failure hospitalization in patients undergoing TAVI (particularly those with low LVEF), though evidence is currently dominated by observational data and displays high heterogeneity.
Limitations
- Predominance of observational study designs introducing potential selection bias and residual confounding
- Heterogeneity across studies in patient characteristics, follow-up durations, and timing of SGLT2 inhibitor initiation
- Variability in the definitions of MACE across the included studies
- Potential for overlapping populations from large research network databases
- Low to very low certainty of evidence by GRADE assessment for several outcomes
- Observational designs inherent to 4 of the 5 included studies leading to residual confounding
- Substantial heterogeneity (I² up to 86%) among studies
- Low certainty of evidence for several outcomes
- Results were sensitive to the choice of meta-analytic model
- Varied definitions of MACE across the included studies
Key expert perspectives
Captured external expert commentary on this paper, strongest first. Original sources are linked where available.
DLDeepak L. BhattDirector, Mount Sinai Fuster Heart Hospital, New York
“I know for me it will be practice changing when I go back to New York next week. I think I am pretty good about making sure that those without contraindications are discharged on an SGLT2 inhibitor. But I must say, in my TAVI or TAVR patients, that's not [been] part of the checklist.”
“Previous trials have provided evidence for SGLT2 inhibitors in patients with a variety of other conditions but have excluded patients with valvular heart disease. Based on our study, if you have a patient undergoing TAVI who is at risk of heart failure, it is important to treat them with dapagliflozin or another SGLT2 inhibitor. These are safe drugs and have a lot of benefit.”
WBWayne BatchelorInterventional cardiologist, Inova Health System
“Basically, if you've had a history of heart failure and you're already on decent guideline-directed medical therapy and you happen to have aortic stenosis, you'll benefit as much as a patient who we would actually treat normally anyway with [dapagliflozin]. To me this is almost just confirming that our normal treatment pattern is valid in patients with aortic stenosis.”
Implication
May support SGLT2 inhibitor initiation post-TAVI in low-LVEF patients; extends prior benefit signals but remains hypothesis-generating without dedicated RCTs.
Abstract
BACKGROUND: Patients undergoing transcatheter aortic valve implantation (TAVI) remain at risk of adverse cardiovascular and renal outcomes despite procedural advancements. Sodium-glucose cotransporter 2 (SGLT2) inhibitors have demonstrated cardiovascular and renal benefits across various patient populations; however, their role in patients undergoing TAVI remains unclear. This study is aimed at evaluating the association between SGLT2 inhibitor use and clinical outcomes in this population. METHODS: We conducted a systematic review and meta-analysis comparing SGLT2 inhibitors versus non-SGLT2 inhibitors or standard care in patients undergoing TAVI. Major databases were searched through March 2026, with Embase updated through June 2026. Pooled analyses were performed using random-effects models to calculate risk ratios (RRs) and mean differences (MDs) with 95% confidence intervals (CIs). RESULTS: Five studies involving 6111 patients (SGLT2 inhibitors: n = 2933; control: n = 3178) were included. In primary random-effects models, SGLT2 inhibitors were associated with lower all-cause mortality (RR 0.68, 95% CI 0.48-0.97, p = 0.03), heart failure (HF) hospitalization (RR 0.62, 95% CI 0.42-0.90, p = 0.01), and major adverse cardiovascular events (RR 0.68, 95% CI 0.48-0.96, p = 0.03). However, in REML/Hartung-Knapp sensitivity analyses, CIs crossed the null for all-cause mortality, HF hospitalization, MACE, and pooled hazard ratios. Mortality benefits were absent at 6 and 12 months and in the randomized trial but persisted in low left ventricular ejection fraction (RR 0.56, 95% CI 0.35-0.89, p = 0.01). No significant differences occurred in acute kidney injury, urinary tract infections, or echocardiographic parameters. CONCLUSION: SGLT2 inhibitor use was associated with lower all-cause mortality and HF hospitalization after TAVI, but the evidence is limited by observational designs, heterogeneity, and low certainty for several outcomes. Further randomized trials are required.
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Cite This Study
Mohamed et al. (2026) conducted a meta-analysis in Aortic stenosis undergoing transcatheter aortic valve implantation (TAVI) (n=6,111). SGLT2 inhibitors vs. Non-SGLT2 inhibitors or standard care was evaluated on All-cause mortality (RR 0.68, 95% CI 0.48-0.97, p=0.03). SGLT2 inhibitors reduced the risk of all-cause mortality by 32% (RR 0.68) compared to standard care or non-use in patients undergoing transcatheter aortic valve implantation.