18-OR: Discontinuation of Renin Angiotensin System Inhibitor and Cardiovascular-Renal Events in Advanced Diabetic Kidney Disease

Abstract

Introduction: Whether angiotensin converting enzyme inhibitors (ACEi) and angiotensin receptor blockers (ARBs) should be discontinued in advanced diabetic kidney disease (DKD) remains controversial. We examined the association of discontinuation of ACEi/ARBs when estimated glomerular filtration rate (eGFR) reached <30 ml/min/1.73m2 with risk of death, major adverse cardiovascular events (MACE) , and end-stage-kidney-disease (ESKD) defined as dialysis and/or eGFR <15/ml/min/1.73m2 in Chinese patients with type 2 diabetes (T2D) . Methods: We performed a prospective analysis of a register including 11,323 patients stratified by continuation of ACEi/ARBs within 6 months of reaching eGFR <30 ml/min/1.73m2 in 2002-2018 followed up until 2019. We used Cox model with time-dependent exposure and covariates to estimate the hazard ratio (HR) of outcomes in the overlap propensity score weighted cohort. Results: Of 11,323 ACEi/ARBs users with new-onset eGFR<30 ml/min/1.73m2, 2,055 (18.5%) discontinued ACEi/ARBs within 6 months whereas 9,268 (81.5%) had continuation of ACEi/ARBs. During a mean follow-up of 4.3 years, 13.5% and 28.4% had incident MACE and ESKD respectively, and 36.2% died. Compared to ACEi/ARBs continuation, discontinuation of ACEi/ARBs was associated with higher risk of MACE (HR=1.26, 95% CI: 1.15-1.39) and ESKD (HR=1.26, 95% CI: 1.14-1.40) , and neutral risk of death (HR=0.96, 95% CI: 0.89-1.04) . Results were consistent when modeling ACEi/ARBs as a time-dependent exposure using a marginal structural model. Conclusions: Discontinuation of ACEi/ARBs was associated with increased risk of cardiovascular-renal events in support of their continued use in patients with advanced DKD. Disclosure M.Shi: None. J.C.Chan: Board Member; Asia Diabetes Foundation, Consultant; Bayer AG, Boehringer Ingelheim International GmbH, Celltrion, Merck Sharp & Dohme Corp., Roche Diabetes Care, Viatris Inc., Research Support; Applied Therapeutics, AstraZeneca, Eli Lilly and Company, Hua Medicine, Servier Laboratories, Stock/Shareholder; GemVCare Ltd. E.Chow: Research Support; Hua Medicine, Medtronic, Powder Pharmaceuticals Inc., Speaker's Bureau; Novartis AG, Sanofi. A.Yang: None. E.S.H.Lau: None. H.Wu: None. X.Zhang: None. B.Fan: None. A.P.Kong: Advisory Panel; Abbott, Kyowa Kirin Co., Ltd., Other Relationship; AstraZeneca, Novo Nordisk, Research Support; Boehringer Ingelheim, Speaker's Bureau; AstraZeneca, Bayer, Eli Lilly and Company, Sanofi, Stock/Shareholder; Aptorum Group Limited. A.Luk: None. R.C.Ma: Other Relationship; Bayer AG, Boehringer Ingelheim International GmbH, Research Support; AstraZeneca, Bayer AG, Novo Nordisk A/S, Pfizer Inc., Tricida, Inc.