Abstract 4370923: Comparative 5-Year Mortality Risk in Stage IV-V Chronic Kidney Disease Patients with Prior Myocardial Infarction: Standard Therapy With versus Without SGLT2 Inhibitors

Introduction: Sodium-glucose cotransporter-2 inhibitors (SGLT2i) are a class of medications that reduce blood glucose levels by inhibiting glucose reabsorption in the proximal convoluted tubules of nephrons to promote glucose excretion. These agents have demonstrated cardioprotective and renoprotective effects, particularly in heart failure and chronic kidney disease (CKD), respectively. However, they are not currently considered standard therapy for patients following myocardial infarction (MI). In this study, we hypothesize that the addition of SGLT2i to standard post-MI therapy reduces mortality in patients with a history of MI and advanced CKD (stages IV or V), despite concerns that SGLT2i are less effective at the low eGFR levels seen in late-stage CKD. Methods: We conducted a retrospective cohort study using de-identified patient data from the TriNetX platform, a global electronic health record (EHR) database comprising 120 healthcare systems worldwide. Two cohorts were established: Cohort A, including patients with a history of MI and stage IV or V CKD who were not taking an SGLT2i, and Cohort B, including similar patients who were taking an SGLT2i in addition to standard post-MI therapy. Propensity score matching was applied to balance baseline comorbidities between cohorts, including hypertension, hyperlipidemia, dyslipidemia, obesity, diabetes, and tobacco use. Results: The five-year mortality rate among patients with prior MI and stage IV or V CKD not receiving an SGLT2i was 33.02% (N=13,637; 4,503 deaths), compared to 21.05% (N=13,632; 2,870 deaths) in those receiving an SGLT2i (P<0.0001; 95% CI [10.92%, 12.01%]; absolute risk difference: 11.97%). The risk ratio was 1.57 (95% CI [1.51, 1.63]), and the odds ratio was 1.85 (95% CI [1.75, 1.95]). Conclusion: This study found a significant reduction in five-year mortality among patients with prior MI and stage IV or V CKD who received SGLT2i in addition to standard post-MI therapy, which includes ACE inhibitors/ARBs, beta-blockers, antiplatelet agents, and high-intensity statins. Although SGLT2i are often avoided in advanced CKD due to perceived diminished efficacy at low eGFR levels, our retrospective analysis of EHR data suggests a novel role for these medications in post-MI management among patients with late-stage CKD. While these findings are promising, they are limited by the retrospective nature of the analysis, and should be confirmed with prospective trials.