Adjunctive Role of SGLT2 Inhibitors in Transthyretin Cardiac Amyloidosis: A Systematic Review and Meta-Analysis

Structured abstractO_ST_ABSBackgroundC_ST_ABSTransthyretin amyloid cardiomyopathy (ATTR-CM) has historically been underdiagnosed but has recently become increasingly recognized due to advances in diagnostic techniques and heightened clinical awareness. Despite this progress, treatment options remain limited, as current approved therapies are costly and not widely accessible. Given the benefits of sodium-glucose cotransporter 2 (SGLT2) inhibitors in broader heart failure (HF) populations, we aimed to evaluate their efficacy in reducing mortality and hospitalizations in ATTR-CM. ObjectivesTo determine whether SGLT2 inhibitors reduce all-cause mortality, CV mortality, and HF hospitalizations in ATTR-CM, offering a potential adjunctive therapy for this undertreated population. MethodsWe performed a systematic review and meta-analysis of SGLT2 inhibitors against SGLT2 inhibitors-naive patients with ATTR-CM. PubMed, Embase, Scopus and Cochrane databases were searched for trials published up to January 31, 2025. Data were extracted from published reports, and quality assessment was performed per Cochrane recommendations. Risk ratios (RRs) with 95% confidence interval (CI) were pooled across trials. Outcomes included all-cause mortality, CV mortality and HF hospitalization. ResultsOut of 177 database results, four observational studies and 5039 patients were included; 2489 (49.39%) received a SGLT2 inhibitor. All-cause mortality (RR 0.44; 95% CI 0.33-0.59; p<0.00001; I{superscript 2}=54%) and CV mortality (RR 0.30; 95% CI 0.16-0.55; p=0.0001; I{superscript 2}=25%) were significantly lower in patients treated with SGLT2 inhibitors compared with control. HF hospitalization (RR 0.68; 95% CI 0.33-1.41; p=0.30; I{superscript 2}=89%) showed a downward trend, yet this was not statistically significant. ConclusionsIn patients with ATTR-CM, SGLT2 inhibitors significantly reduce both all-cause and cardiovascular mortality compared to standard care, suggesting they may serve as a valuable adjunctive therapy for this undertreated population. Although HF hospitalization showed a nonsignificant downward trend, these findings underscore the need for large randomized trials to confirm and expand on these promising results.