Graphical abstract
I enjoyed reading the recently published retrospective cohort study by Yasmin et al1 in which they found that heart failure patients who have undergone transcatheter aortic valve replacement (TAVR) had a lower rate of hospitalization if they were prescribed a sodium-glucose co-transporter 2 inhibitor (SGLT2i). However, I am concerned that their index event settings may underestimate the risk of adverse outcomes in their SGLT2i cohort.
The authors repeatedly state that the index date for the SGLT2i cohort was defined as the date of SGLT2i prescription. However, the only index date possible for the control cohort is the date of their heart failure or TAVR procedure. This is important as patients are more likely to experience adverse health outcomes such as hospitalization in the acute period (ie first 7 days) following a heart failure diagnosis.2 When I analyzed the replicated SGLT2i cohort (n = 3,715), I found that 43.6% (n = 1,621) had received their index SGLT2i prescription at least 1 week following their heart failure diagnosis or TAVR procedure.∗ This means that almost half of the treatment cohort’s outcome period missed this acute period. This would heavily bias the outcomes of the study in the favor of the treatment cohort, regardless of the drug analyzed.
To demonstrate this, I constructed a negative control study replacing SGLT2i criteria with Botox.∗ This analysis was performed on the January 20, 2026, using the same methods reported in the original study. Following identical propensity score matching processes to the original study, the resulting Kaplan-Meier survival analysis demonstrates the same trend (Figure 1): an immediate increase in hospitalization for the control cohort corresponding to the acute postheart failure/TAVR period, followed by a lack of divergence between the cohorts. These data suggest that SGLT2i use in heart failure patients with TAVR may not be correlated with reduced hospitalization.
Figure 1.
Kaplan-Meier Time-To-Event Free Curves of Hospitalization
(A) SGLT2i users and nonusers and (B) botulinum toxin users and nonusers. SGLT2i = sodium-glucose co-transporter 2 inhibitor.
Footnotes
The author has reported that they have no relationships relevant to the contents of this paper to disclose.
The author attests they are in compliance with human studies committees and animal welfare regulations of the author’s institution and Food and Drug Administration guidelines, including patient consent where appropriate. For more information, visit the Author Center.
Full details on how these replications were performed are available at the following link: https://data.mendeley.com/preview/mbnydkct27?a=8a5f3226-6114-4331-acd6-b0b980958b14.
References
- 1.Yasmin F., Hamza M., Fahim M.A.A., Asghar M.S., Ullah W., Alraies M.C. Sodium glucose Co-Transporter 2 inhibitors in patients with heart failure and transcatheter aortic valve replacement. JACC Adv. 2026;5(2) doi: 10.1016/j.jacadv.2025.102462. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 2.Loosen S.H., Roderburg C., Curth O., et al. The spectrum of comorbidities at the initial diagnosis of heart failure a case control study. Sci Rep. 2022;12(1):2670. doi: 10.1038/s41598-022-06618-5. [DOI] [PMC free article] [PubMed] [Google Scholar]