926-P: Early Sodium–Glucose Cotransporter 2 Inhibitors–Induced Change in Haematocrit as a Predictor of Mortality and Cardiovascular Risk—A Real-World Study

Introduction & Objective: Statistical and mechanistic evidence suggest that sodium-glucose co-transporter 2 inhibitors (SGLT2i)-induced change in haematocrit may affect cardiovascular risk. Since the magnitude of change is variable but manifested early, we explored whether the within 6-month changes in haematocrit in subjects initiated with SGLT2i could help identify those who would benefit most in terms of cardiovascular risk reduction. Methods: Using real-world data in GPRD GOLD and Aurum, a series of open cohort studies were performed in individuals with diabetes mellitus type 2 (T2DM). Primary outcome was composite end-point including all-cause mortality, myocardial infarction ischaemic heart disease and stroke. Based on linearity analyses and clinical interpretability, individuals were categorised into three subgroups of the observed absolute haematocrit change (“negative”, “positive” = 0-4, “highly positive”=>4). Primary analysis was conducted with competing cox proportional hazard model with restricted cubic spline. Results: A total of 37,2336 individuals, over 40 years-old, with T2DM under treatment with SGLT2i were included and followed for ~2.4 years with a total observation worth of ~86000 person-years. The subgroup with the negative haematocrit change was found to be at a significantly increased risk of manifesting the composite outcome [adjusted hazard ratio and 95% confidence intervals, aHR (95% CI): 1.23 (1.12, 1.36)], death from any cause [1.33 (1.19,1.49]) and heart failure [1.35 (1.14, 1.60)], compared to the reference group. 0-9.83%). Sensitivity analyses did not alter the findings. Conclusion: Among individuals with T2DM at low baseline risk of cardiovascular disease, an early increase in haematocrit after SGLT2i institution may be regarded as an indicator of future cardiovascular benefit.