Clinical Outcomes of Intravenous Iron Therapy in Systolic Heart Failure Patients Receiving SGLT2 Inhibitors

SGLT2 inhibitors (SGLT2i) can mimic iron deficiency (ID) by altering iron biomarkers. Although intravenous (IV) iron therapy is an established treatment for ID in HF, it remains unclear whether concomitant use of IV iron and SGLT2i increases the risk of thromboembolic events (TE). We aim to evaluate the risks associated with combined IV iron therapy and SGLT2i in patients with systolic HF and ID. Using the TriNetX database, we identified patients with systolic HF on SGLT2i at baseline with a diagnosis of ID (serum ferritin <100 μg/L). Patients were stratified by IV iron therapy use. Propensity score matching was used to balance confounding factors between groups. Cox proportional hazard ratio was calculated for TE, all-cause mortality, major adverse cardiovascular events (MACE), and HF exacerbation over a 1-year follow-up. Of 16,660 patients, 3,434 (20.6%) received IV iron therapy. The mean age in the treatment group and the control group was 65.1 years (52.4% male) and 66.0 years (54.7% male), respectively. IV iron treatment was associated with significantly increased risks of TE (HR: 1.56; 95% CI: 1.19-2.06; p = 0.001), MACE (HR: 1.51; 95% CI: 1.28-1.78; p = 0.007), all-cause mortality (HR: 1.55; 95% CI: 1.36-1.77; p < 0.001), and HF exacerbation (HR: 1.41; 95% CI: 1.12-1.77; p = 0.003). Patients with systolic HF and ID receiving combined IV iron therapy and SGLT2 inhibitors had significantly increased risks of TE, MACE, all-cause mortality, and HF exacerbations. Further mechanistic studies are required to elucidate the interactions between IV iron and SGLT2i.