SGLT-2 Inhibitors and Outcomes After Transcatheter Aortic Valve Implantation
Key result
Peri-operative SGLT2 inhibitor use is linked to ~35% lower MACE risk after TAVI.
- HR 0.65
- 95% CI 0.44-0.95
- P=0.03
- n=35,075
Figures
Why the study?
Does peri-operative SGLT-2 inhibitor use reduce major adverse cardiovascular events, heart failure hospitalizations, and mortality in patients with aortic stenosis undergoing transcatheter aortic valve implantation?
Key Points
- To assess the association between sodium-glucose co-transporter 2 inhibitor (SGLT-2i) use and clinical outcomes in patients undergoing transcatheter aortic valve implantation (TAVI).
- Systematic search across PubMed, Cochrane Library, Google Scholar, ScienceDirect, and ClinicalTrials.gov for RCTs and observational studies.
- Included 6 studies (1 RCT, 5 cohort studies) comprising 35,075 patients undergoing TAVI (6,207 receiving SGLT-2i and 28,868 controls).
- Pooled adjusted HRs and risk ratios for time-to-event and dichotomous clinical outcomes, assessing risk of bias with RoB 2.0 and ROBINS-I alongside GRADE certainty ratings.
- SGLT-2i use was associated with a significant reduction in major adverse cardiovascular events (pooled HR: 0.65; 95% CI: 0.44-0.95; P = 0.03; I² = 26%) and heart failure hospitalization (pooled HR: 0.58; 95% CI: 0.40-0.86; P = 0.007; I² = 59%).
- All-cause mortality was significantly lower in the SGLT-2i group (pooled HR: 0.71; 95% CI: 0.55-0.91; P = 0.007; I² = 75%), as was cardiovascular death (pooled RR: 0.55; 95% CI: 0.34-0.89; P = 0.01; I² = 36%).
- Certainty of evidence was graded low to very low across outcomes due to high heterogeneity, observational designs, and potential confounding.
Study Design
Type
Meta-Analysis (n=35,075)
Multicenter
Yes
Structured PICO
Does peri-operative SGLT-2 inhibitor use reduce major adverse cardiovascular events, heart failure hospitalizations, and mortality in patients with aortic stenosis undergoing transcatheter aortic valve implantation?
P
Population
35,075 older adults (mean age 73.0 to 82.4 years across 6 studies) with severe aortic stenosis undergoing TAVI, followed for a median of 2.6 months to 5 years.
I
Intervention
Sodium glucose co-transporter 2 inhibitors (SGLT-2i) as a class (including empagliflozin, dapagliflozin, canagliflozin, and ertugliflozin) used in the preoperative, peri-operative, or postoperative management of TAVI.
C
Comparator
Standard care or no SGLT-2 inhibitor.
O
Outcome
Major adverse cardiovascular events (MACE), defined as a composite of heart failure hospitalizations and any death, assessed at 1 year to 2 years post-TAVI.composite
Main Result
Hazard Ratio: 0.65 (95% CI 0.44–0.95)
p-value: p=0.03
Limitations
- Predominance of retrospective observational studies (5 of 6 studies) susceptible to residual confounding and selection bias
- Reliance on ICD-10 diagnostic coding for clinical endpoints lacking core-laboratory adjudication
- Medication exposure determined by prescription records without confirming adherence or duration
- Unavailable procedural factors (e.g., valve type, residual aortic regurgitation, pacemaker rates) in registry datasets
- Substantial clinical and methodological heterogeneity across timing of initiation, patient populations, and follow-up duration
- Predominance of elderly males from high-income countries limiting generalizability
- Inability to perform subgroup analysis for low-flow low-gradient aortic stenosis or formal pooled safety analysis
- Predominance of retrospective observational designs (5 out of 6 studies), which are susceptible to residual confounding, selection bias, and treatment-indication bias.
- Reliance on ICD-10 diagnostic coding for defining clinical endpoints rather than core-laboratory adjudicated data.
- Medication exposure was primarily determined by prescription records, which do not necessarily reflect long-term patient adherence or treatment duration.
- Key procedural factors (such as valve type, commissural alignment, residual aortic regurgitation, pacemaker implantation rates) were largely unavailable in registry datasets.
- Substantial clinical and methodological heterogeneity across studies in timing of SGLT-2i initiation, patient populations, and follow-up durations.
Key expert perspectives
Captured external expert commentary on this paper, strongest first. Original sources are linked where available.
“Previous trials have provided evidence for SGLT-2 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 SGLT-2 inhibitor. These are safe drugs and have a lot of benefit.”
“We found that these drugs are safe even in our elderly population, who are usually excluded from clinical trials. It is important to have evidence in this group of patients; it is good for science and good for physicians to have an independent trial to demonstrate that the [beneficial] effect of SGLT-2 inhibitors is also consistent in subgroups of patients in whom we didn't have evidence until now.”
“Among elderly patients with aortic stenosis undergoing TAVI and at high risk for heart failure, dapagliflozin was safe and reduced the incidence of all-cause death or worsening heart failure compared with standard care.”
Implication
This meta-analysis demonstrates that peri-operative SGLT-2 inhibitor use in patients undergoing TAVI is associated with significantly lower risks of MACE, heart failure hospitalization, all-cause mortality, and cardiovascular death, though the certainty of evidence is low due to the predominance of observational data.
Abstract
Background: Despite successful transcatheter aortic valve implantation (TAVI) for severe aortic stenosis, residual heart failure risk and postprocedural complications persist. Objectives: The aim was to assess the association between sodium glucose co-transporter 2 inhibitor (SGLT-2i) use and clinical outcomes in patients undergoing TAVI. Methods: A systematic search was conducted across PubMed, Cochrane Library, Google Scholar, ScienceDirect, and ClinicalTrials.gov for eligible randomized controlled trials (RCTs) and observational studies. Adjusted HRs and risk ratios were pooled for time-to-event outcomes and dichotomous outcomes, respectively. Risk of bias was assessed using the Risk of Bias 2.0 and Risk of Bias in Non-randomized Studies of Interventions-I tools for RCTs and cohort studies, respectively. Results: Six studies (1 RCT, 5 cohorts) including 35,075 patients were included in the analysis. In pooled analyses, SGLT-2i use was associated with a significantly lower risk of major adverse cardiovascular events (pooled HR: 0.65; 95% CI: 0.44-0.95; P = 0.03; I 2 = 26%), heart failure hospitalization (pooled HR: 0.58; 95% CI: 0.40-0.86; I 2 = 59%; P = 0.007), all-cause mortality (pooled HR: 0.71; 95% CI: 0.55-0.91; P = 0.007; I 2 = 75%), and cardiovascular death (pooled risk ratio: 0.55; 95% CI: 0.34-0.89; P = 0.01; I 2 = 36%). The Grading of Recommendations Assessment, Development, and Evaluation assessment was downgraded due to heterogeneity, potential bias, and nonrandomized design of studies. Conclusions: This meta-analysis suggests that peri-operative SGLT-2i use was associated with lower cardiovascular events post-TAVI albeit with low certainty due to predominance of observational studies. These findings are hypothesis generating rather than causal inference. Future clinical trials are warranted.
Discussion
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Cite This Study
Mohammed et al. (2026) conducted a meta-analysis in Severe aortic stenosis undergoing transcatheter aortic valve implantation (TAVI) (n=35,075). Sodium glucose co-transporter 2 inhibitors (SGLT-2i: empagliflozin, dapagliflozin, canagliflozin, ertugliflozin) vs. Standard care or no SGLT-2 inhibitor was evaluated on Major adverse cardiovascular events (MACE, composite of heart failure hospitalizations and any death) (HR 0.65, 95% CI 0.44-0.95, p=0.03). Peri-operative SGLT-2 inhibitor use was associated with a lower risk of MACE after TAVI compared to control (pooled HR 0.65; 95% CI 0.44-0.95; P = 0.03).