WCN26-8163 Impact of renin-angiotensin system inhibitors discontinuation in advanced chronic kidney disease: a target trial emulation
Résumé
Introduction Renin-angiotensin system (RAS) inhibitors are a cornerstone of the treatment strategy aiming at reducing kidney and cardiovascular risks in patients with chronic kidney disease (CKD). However, it is common practice to stop RAS inhibitors in advanced CKD stages, as an attempt to avoid drug-related adverse effects and/or to delay initiation of kidney replacement therapy (KRT). Methods From the CKD-Renal Epidemiology and Information Network prospective cohort study, we selected participants with an estimated glomerular filtration rate (eGFR) <30 mL/min/1.73m2 and treated with RAS inhibitors for at least 3 months. We performed a target trial emulation with parametric g-formula to compare two treatment strategies: to discontinue or to continue RAS inhibitors. Potential time-fixed and varying confounding factors included age, sex, diabetes, heart failure, respiratory disease, eGFR, systolic blood pressure, serum sodium and potassium, and drug prescriptions. Study outcomes were the composite of cardiovascular death, myocardial infarction, stroke or hospitalization for heart failure, i.e. major cardiovascular events (MACE), and KRT initiation. Results Among the 1,434 patients included (median age 68 years, median eGFR 25mL/min/1.73m2, 35% women), 386 (27%) discontinued RAS inhibitors over a median follow-up of 35 months. The 3-year adjusted relative risk of MACE associated to discontinuing RAS inhibitors, compared to continuing, was 2.02 (95% CI, 1.62 to 2.47), and that of KRT initiation, 1.34 (95% CI, 1.14 to 1.60). Conclusion RAS inhibitor discontinuation was strongly associated with MACE and KRT risks, the leading causes of morbidity and mortality in advanced CKD. Our results, along with other published data, suggest that the risk-benefit balance favors continued use of RAS inhibitors in this population.
