Impact of sodium- glucose co-transporter 2 inhibitors in mortality and Decongestion in cardiac amyloidosis: A systematic review and meta-analysis

Abstract

Background

While Sodium glucose Co-transporter 2 inhibitors (SGLT2i) show proven benefits in heart failure with preserved ejection fraction (HFpEF), their role in transthyretin cardiac amyloidosis (ATTR-CA) remains uncertain. This meta-analysis evaluates SGLT2i efficacy and safety specifically in ATTR-CA patients, a population excluded from pivotal trials.

Materials and Methods

Following PRISMA guidelines, we systematically searched PubMed/Embase/Cochrane through December 2024 for studies assessing SGLT2i in cardiac amyloidosis. Primary outcomes included all-cause mortality, cardiovascular mortality, NT-proBNP levels, and hospitalizations. Risk Ratios (RR) and Hazard Ratios (HR) with 95 % confidence intervals (CIs) were used to compare treatment effects for categorical endpoints. Continuous outcomes were compared with mean differences (MD).

Results

Five observational studies (5101 patients; 2528 SGLT2i vs 2573 controls) met inclusion criteria. SGLT2i use was associated with significantly lower all-cause mortality (RR 0.37, 95 % CI 0.28-0.49, p < 0.00001, I²=12 %) and cardiovascular mortality (RR 0.30, 0.16-0.55, p < 0.00001, I²=25 %). NT-proBNP levels were significantly reduced (MD -299.66 pg/mL, -493.24 to -106.08, p = 0.002, I²=0 %) and hospitalization rates were significantly lower (HR 0,59, 95 %CI 0,38-0,90; p = 0,01, I²=0 %). Most studies had moderate bias risk, primarily from retrospective designs and selection bias.

Conclusions

In ATTR-CA patients, SGLT2i were associated with 63-70 % relative risk reduction in mortality and improved cardiac biomarkers and hospitalization rates. While promising, these observational findings require confirmation in randomized trials to address potential confounding factors.