Sodium-glucose cotransporter 2 inhibitors for transthyretin amyloid cardiomyopathy: a systematic review and meta-analysis

Abstract Introduction Sodium-glucose cotransporter 2 inhibitors (SGLT2i) are indicated for both heart failure with preserved ejection fraction (HFpEF) and heart failure with reduced ejection fraction (HFrEF). However, the efficacy of SGLT2i in patients with transthyretin amyloid cardiomyopathy (ATTR-CM) remains unknown. Purpose This systematic review and meta-analysis aimed to evaluate clinical and laboratory outcomes in ATTR-CM patients treated with SGLT2i. Methods We searched PubMed, Embase, and Cochrane for studies comparing ATTR-CM patients receiving SGLT2i to those receiving standard therapy. The results are presented as risk ratio (RR) or mean difference (MD), with a 95% confidence interval (CI). Heterogeneity was assessed using I² statistics and statistical analysis was performed with RevMan (version 8.16.0). Results A total of 1,145 patients from 6 observational studies were included, of whom 479 (41.8%) received SGLT2i. The participants had a mean age of 79.8 ± 2.1 years, a mean left ventricular ejection fraction of 50.6 ± 3.7%, and a mean systolic blood pressure of 125.5 ± 4.23 mmHg. The follow-up ranged from 3 to 31.2 months. All-cause mortality (RR 0.37, 95% CI 0.27 to 0.49, p 0.00001, figure 1A) and cardiovascular mortality (RR 0.30, 95% CI 0.16 to 0.55, p 0.0001, figure 1B) were significantly lower in the SGLT2i group. Additionally, SGLT2i therapy was associated with an attenuated rate of increase in plasma NT-proBNP (N-terminal pro B-type natriuretic peptide) (MD -530.76 pg/mL, 95% CI -578.91 to -482.62, p 0.00001, figure 2A), while improving the estimated glomerular filtration rate (MD 3.33 mL/min/1.73m², 95% CI 0.95 to 5.71, p = 0.006, figure 2B). Conclusion The use of SGLT2i significantly reduces mortality, attenuates the increase of NT-proBNP, and improves renal function in patients with ATTR-CM. However, randomised clinical trials are needed to further investigate the efficacy of SGLT2i therapy in this population.