Discontinuation of Renin–Angiotensin System Inhibitors and Risk of End‐Stage Renal Disease and Cardiovascular Outcomes Among Patients With Type 2 Diabetes and Chronic Kidney Disease: A Nationwide Taiwanese Cohort Study

ABSTRACT Purpose This nationwide cohort study examined the effects of discontinuation versus continuation of renin–angiotensin system inhibitors (RASis) on major renal and cardiovascular outcomes after the estimated glomerular filtration rate (eGFR) decreased to below 45 mL/min/1.73 m 2 in patients with type 2 diabetes and treated with RASis. Methods Using linked Taiwanese databases with claims and clinical data, we identified patients with type 2 diabetes who used RASis during 2016–2020, and either discontinued or continued RASis within 180 days when their eGFR fell below 45 mL/min/1.73 m 2 . The outcomes of interest included end‐stage renal disease (ESRD), myocardial infarction, stroke, heart failure, and all‐cause mortality. We estimated the hazard ratios (HRs) and 95% confidence intervals (CIs) for RASi discontinuation versus RASi continuation using on‐treatment and intention‐to‐treat analyses and inverse probability weighting to adjust for baseline and time‐varying covariates. Results We identified 251 853 eligible patients, of whom 37 108 (15%) discontinued RASis and 214 745 (85%) continued RASis. The on‐treatment HR associated with RASi discontinuation was 2.52 (95% CI, 2.33–2.73) for ESRD, 1.18 (1.08–1.30) for myocardial infarction, 1.28 (1.19–1.37) for stroke, 1.18 (1.13–1.24) for heart failure, and 1.77 (1.70–1.84) for all‐cause mortality. Results from the intention‐to‐treat analysis were similar, albeit more conservative. Findings remained consistent across eGFR strata (≥ 30 to < 45 and < 30 mL/min/1.73 m 2 ), urine albumin‐creatinine ratio categories (≥ 300 and < 300 mg/g), and patient subgroups with various baseline characteristics. Conclusion Our results support continuing RASi treatment even when the eGFR declines to below 45 mL/min/1.73 m 2 based on potential renal, cardiovascular, and survival benefits.