SGLT2 Inhibitors and Cardiovascular Outcomes in Patients With Fabry Disease: Observations From a Federated Research Network

BACKGROUND AND AIM: Fabry disease (FD) is frequently complicated by renal impairment and cardiovascular events; however, evidence on sodium-glucose cotransporter-2 inhibitors (SGLT2i) in this population is scarce. Accordingly, we assessed the association between SGLT2i exposure and cardiovascular outcomes in adults with FD. Patients were stratified by SGLT2 inhibitor exposure. The primary outcome was a composite of all-cause death, acute myocardial infarction and acute or acute-on-chronic heart failure at 2 and 5 years; secondary outcomes included individual components and progression to advanced kidney disease. Patients with prior non-fatal outcomes were excluded from the respective analyses. Propensity score matching (1:1) and Cox proportional hazards models were used. Sensitivity analyses included alternative follow-up periods, restriction to Fabry disease diagnosed from 2013 onwards and a stricter Fabry disease definition requiring ≥ 2 diagnoses; subgroup analyses were performed by sex and age. RESULTS: Among 14 940 FD patients, 1028 (6.9%) had recorded exposure to SGLT2 inhibitors (mean age: 65.5 ± 12.0 years; 53.0% male), who were older and had a higher comorbidity burden and worse baseline renal profile than non-exposed patients. After PSM, 732 patients per group (exposed and non-exposed patients) were available for analysis. At 2 years, SGLT2i exposure was associated with a lower risk of the composite outcome (HR 0.61; 95% CI 0.38-0.97) and all-cause death (HR 0.56; 95% CI 0.33-0.95). At 5 years, results were consistent for the composite outcome (HR 0.56; 95% CI 0.39-0.79) and all-cause death (HR 0.62; 95% CI 0.42-0.93), with reduced myocardial infarction risk (HR 0.53; 95% CI 0.30-0.90). CONCLUSIONS: In a large real-world FD cohort, SGLT2i exposure was associated with lower cardiovascular risk and mortality, supporting further prospective investigation.