Erythrocytosis incidence and thromboembolic risk in heart failure with reduced ejection fraction treated with SGLT2 inhibitors: a nationwide register-based cohort study

BACKGROUND: Sodium-glucose cotransporter-2 inhibitors (SGLT2i) increase haemoglobin and haematocrit levels, potentially causing secondary erythrocytosis-defined as a haemoglobin level above 16.5 g/dL in men and 16.0 g/dL in women-which is associated with an elevated thromboembolic risk. This study investigated the incidence of erythrocytosis and its association with thromboembolic events in patients with heart failure with reduced ejection fraction (HFrEF) treated with SGLT2i.

METHODS: In this nationwide cohort study, we included 3138 patients with new-onset HFrEF who initiated SGLT2i treatment after diagnosis, and 3138 propensity score-matched untreated controls. Haemoglobin was measured at baseline and six-month follow-up. Erythrocytosis incidence at follow-up was assessed using Poisson regression. Cox models were used to evaluate the association between erythrocytosis and one-year risk of fatal and non-fatal thromboembolic events (myocardial infarction, stroke, pulmonary embolism, or deep venous thrombosis), stratified by SGLT2i treatment.

RESULTS: Erythrocytosis developed in 207 patients (3.3%). Incidence was higher among SGLT2i-treated patients (109.5 vs. 26.8 per 1000 person-years), with an adjusted incidence rate ratio of 4.10 (95% CI 2.95-5.83). No significant association was observed between erythrocytosis and one-year thromboembolic risk in the total population (HR: 0.85 95% CI 0.44-1.65), even when stratified by SGLT2i-treated (HR: 0.81 95% CI 0.38-1.74) and untreated patients (HR: 0.75, 95% CI 0.19-3.05) (interaction P = 0.77).

CONCLUSION: Although erythrocytosis incidence was higher in SGLT2i-treated HFrEF patients, it was not associated with an increased one-year thromboembolic risk.