A Systematic Review and Meta-Analysis of the Safety and Efficacy of SGLT2 Inhibitors in Chronic Heart Failure in ACHD Patients

Background

Sodium-glucose cotransporter 2 inhibitors (SGLT2is) have become a first-line therapy for heart failure (HF) in adults. However, data on their use in HF associated with adult congenital heart disease (ACHD) are limited. This systematic review and meta-analysis evaluated the safety, tolerability, and efficacy of SGLT2is in ACHD HF patients, supplementing guideline-directed medical therapy.

Methods

A comprehensive systematic search and meta-analysis were conducted on studies examining SGLT2i use in ACHD HF patients. The primary endpoint was the change in the New York Heart Association (NYHA) functional class (FC), with secondary endpoints including changes in ventricular function and N-terminal pro B-type natriuretic peptide (NT-proBNP) levels. Additionally, the safety and tolerability of SGLT2is were evaluated.

Results

The meta-analysis included eight studies with 287 patients aged 19–67 years (median age 37.5 years). Adding SGLT2is to combined therapies significantly improved NYHA FC (log odds ratio 1.3, 95% confidence interval [CI] 0.37–2.23, p = 0.01) and reduced NT-proBNP levels (mean difference [MD] −0.43, 95% CI −0.70 to −0.16, p < 0.001). A notable decrease in systolic blood pressure was observed (MD −0.32, 95% CI −0.51 to −0.14, p = 0.00). The adverse effect profile was comparable to that seen in routine HF, with fewer HF hospitalizations post-SGLT2i initiation. Urinary tract infections occurred in 14 patients (5%), with no instances of hypoglycemia or ketoacidosis reported. Medication withdrawal due to adverse effects was noted in 19 patients (7%).

Conclusions

SGLT2is are well tolerated in ACHD HF patients. Notably, SGLT2is improved NYHA FC and reduced NT-proBNP levels across a diverse ACHD HF patient cohort. However, further prospective, multicenter studies are needed to confirm the safety and efficacy of SGLT2is in this unique patient population.