181-OR: Declining eGFR over Time Predicts the Risk of a Composite of Primary or Secondary Major Adverse Cardiovascular Events or Heart Failure Hospitalization, in People with Type 2 Diabetes—EXSCEL Post Hoc analysis

Introduction and Objective: Declining estimated glomerular filtration rate (eGFR) is a predictor for the development and progression of chronic kidney disease and incident cardiovascular disease (CVD). We used a novel statistical approach to investigate the role of eGFR decline in predicting CVD events in people with type 2 diabetes, in both primary and secondary CVD prevention settings.

Methods: Bayesian joint modelling of eGFR repeated measures and time to CVD event was applied to the Exenatide Study of Cardiovascular Event Lowering (EXSCEL) to examine the association between declining eGFR and the incidence of MACEhF (non-fatal myocardial infarction, non-fatal stroke, cardiovascular death, or hospitalization for heart failure), adjusting for age, sex, smoking, hypertension, antihypertensive medication, hyperlipidemia, lipid lowering medication, diabetes duration, atrial fibrillation, HDL-C, total cholesterol, HbA1c and treatment allocation (once-weekly exenatide or placebo).

Results: Data from 11374 trial participants with (n=8135) and without (n=3239) previous history of CVD were analyzed. The mean (SD) eGFR slope/year in participants without and with a history of CVD was -0.69 (1.73) and -0.97 (2.04) respectively. The corresponding 5-year MACEhF incidences were 7.6% (95% CI 6.3-8.9%) and 21% (95% CI 19-22%). A 1 SD decrease in the eGFR slope was associated with increased MACEhF risks of 64% (HR 1.64, 95% CI 1.15-2.28, p=0.007) and 22% (HR 1.22, 95%CI 1.03-1.45, p=0.026), respectively.

Conclusion: Declining eGFR over time is a significant predictor of incident MACEhF events in people with type 2 diabetes, both those with and without existing CVD, with a higher hazard ratio for MACEhF in the latter group.