2-045 Reducing cardiovascular and renal outcomes via early sodium-glucose co-transporter-2 inhibitor therapy in patients with type 2 diabetes mellitus and acute coronary syndrome- A propensity score matched multi-model retrospective registry analysis

Introduction Sodium-glucose co-transporter inhibitors (SGLT2is) are indicated to reduce cardiovascular events in individuals with type 2 diabetes mellitus (T2DM) and stable atherosclerotic cardiovascular disease. However, due to lack of evidence, concerns of use in acute coronary syndromes (ACS) remain despite patients being at highest risk of further cardiovascular and renal events, where early SGLT2is may offer greater risk reduction in terms of these outcomes. Purpose To assess real world evidence of the impact of early SGLT2i therapy when prescribed at discharge, in comparison to those that receive it late i.e. post discharge and those that never receive it, in the reduction in major adverse cardiovascular events (MACE) and renal events in patients with T2DM presenting with ACS. Methods A retrospective, registry-based, observational study of T2DM patients surviving an ACS event, eligible for an SGLT2i admitted between July 2018 and December 2023. Comparisons were made between patients receiving SGLT2is at discharge with those who never received it or were prescribed post-discharge any time during the follow up period. The primary outcomes were the proportion of patients having a first (i) MACE event (i.e., a composite of first events of hospitalisation for heart failure (HHF), coronary, cerebrovascular events or all-cause death) (ii) acute kidney injury (AKI) after discharge and during the follow up period. Inter-group survival analysis was performed using propensity score-matched Cox-proportional hazards regression model with further adjustment to account for death as a competing factor using the sub-distribution and time variable hazard models. Visual representation was made using Kaplan Meier survival analysis. Results Of 970 patients, 313 received an SGLT2i at discharge, 342 post-discharge, while 315 patients never received it. The incidence of primary outcomes, as measured in events per 100 patient years, were 10.4, 8.1 and 22.6 for first MACE and 6.7, 6.4, and 9.3 for first AKI respectively. Receiving SGLT2is at discharge significantly reduced the risk of MACE (hazard ratio [HR] 0.38, 95% confidence interval [CI] 0.26-0.58, p<0.001) when compared to those who never received with similar findings for first AKI events between the two groups (HR 0.62 [0.39-0.94], p=0.039). Although non-significant, SGLT2i initiation at discharge (vs. post discharge) was associated with a lower risk of AKI (HR 0.94 [0.60-1.51], p=0.452]). Similarly, although no significant difference was noted for discharge vs post discharge SGLT2i initiation in terms of MACE (HR 1.24 [0.89- 1.83], p=0.253), of the individual components of MACE when adjusted for death as a competing outcome, a significant reduction in HHF (HR 0.43 [0.22-0.86],p=0.017) and myocardial infarction (MI) (HR 0.47 [0.27-0.81],p=0.007) was noted favouring early therapy. Conclusion The above real world evidence suggests that discharge SLGT2i therapy significantly reduces first events of MACE and AKI in T2DM-ACS patients in comparison to SGLT2i naïve patients. Early SGLT2i therapy is associated with a significant reduction in first events of HHF and MI and non-significant reduction in AKI in comparison to delayed initiation. Funding This work was partially supported by an award from EFSD/Boehringer Ingelheim European Research Programme on ‘Multi-System Challenges in Diabetes’.