Safety of sodium-glucose cotransporter-2 inhibitor in low body mass index patients who have heart failure with reduced ejection fraction

초록

Background: The standard treatment strategy of heart failure with reduced ejection fraction (HFrEF) has become based on combination therapy of four drugs including sodium-glucose cotransporter-2 inhibitor (SGLT2i). Because of weight-lowering effect of SGLT2i, its safety in underweight patients is questionable. We aimed to evaluate the safety of SGLT2i in underweight patients using a data from the SMILE-HF registry. Methods: The SMILE-HF registry, a multicenter observational study, enrolled 1,976 patients hospitalized for acute heart failure from 2019 to 2024. There were 750 patients with HFrEF, and underweight was defined as a body mass index (BMI) 20 or less. The mortality and readmission rates at 1 year, changes in renal function, and body weight were compared between the non-underweight and underweight groups. Results: Among 750 HFrEF patients, 255 patients (34 %) used SGLT2i. At the time of recruitment of study subjects, SGLT2i was not covered by insurance for heart failure, so the proportion of patients using SGLT2i was low. Among 255, there were 32 patients (12.5 %) in the underweight group. The mean weight of the underweight group was 48.7 ± 7.4 kilogram, and the mean BMI was 18.4 ± 1.4. The mean serum creatinine of the two groups was similar at 1.1 ± 0.5 mg/dL, and there was no statistical difference in estimated glomerular filtration rate. About 75% of SGLT2i patients were administered dapaglifloxin, and about 25% were administered empaglifloxin. Composite of mortality and readmission rate at 1 year were 18.8% in the underweight group and 12.1% in the non-underweight group, which was higher in the underweight group but not statistically significant. The rate of decline in eGFR by 40% or more was also higher in the underweight group, but there was no statistical difference. Weight at 1 year was not significantly different from that at discharge. Conclusion: Caution would be required in underweight HFrEF patients who are taking SGLT2i because it may cause worsening of clinical outcomes and renal function. This is a limited data set and further analysis is necessary.