Sodium-glucose cotransporter 2 inhibitors and outcomes in transthyretin amyloid cardiomyopathy: Systematic review and meta-analysis

Background

Transthyretin amyloid cardiomyopathy (ATTR-CM) commonly leads to heart failure but has traditionally been an exclusion criterion in randomized clinical trials (RCTs) of sodium-glucose cotransporter 2 inhibitors (SGLT2i); therefore, the effects of these drugs in this population remain undocumented. In light of recent studies, this meta-analysis aimed to investigate the effect of SGLT2i on the prognosis of patients with ATTR-CM.

Methods

A comprehensive search of Medline, Scopus, and the Cochrane Library was conducted up to November 17, 2024. Study selection, data extraction and quality assessment were carried out independently by two investigators. Associations of SGLT2i with outcomes were pooled using random-effects meta-analyses.

Results

A total of five studies (9766 participants, 4 propensity score-matched) were included. The use of SGLT2i was associated with significant reductions in all-cause mortality [hazard ratio (HR) .54, 95% confidence interval (CI) .44–.66], cardiovascular mortality (HR .39, 95% CI .23–.65), major adverse cardiovascular events (HR .71, 95% CI .61–.83), and heart failure hospitalizations (HFHs) (HR .63, 95% CI .52–.77) compared to non-use. The odds of cardiac arrhythmias were significantly lower among SGLT2i users compared to non-users [odds ratio (OR) .73, 95% CI .65–.83]. Specifically, SGLT2i use was associated with significant reductions in the odds of atrial fibrillation (AF) (OR .75, 95% CI .62–.91), ventricular tachycardia (OR .72, 95% CI .59–.88), and sudden cardiac arrest (OR .71, 95% CI .50–.99).

Conclusions

The use of SGLT2is may be associated with a more favourable prognosis in patients with ATTR-CM. Adequately powered, long-term RCTs are required to validate the available observational evidence.