A systematic review and meta-analysis of the clinical impact of stopping renin–angiotensin system inhibitor in patients with chronic kidney disease

Although renin–angiotensin system (RAS) inhibitors reduce the risk of cardiovascular diseases and end-stage kidney disease (ESKD) in chronic kidney disease (CKD) patients, they are often discontinued in clinical practice due to drug-related adverse events. However, limited evidence is available about the clinical impact of RAS inhibitor discontinuation in CKD patients. A comprehensive search of publications investigating the effect of discontinuing RAS inhibitors on clinical outcomes in CKD patients in PubMed, the Cochrane Library, and Web of Science was conducted (inception to November 7, 2022), and potentially relevant studies were searched by hand (through November 30, 2022). Two reviewers independently extracted data according to the PRISMA and MOOSE guidelines and assessed the quality of each study with risk-of-bias tools, RoB2 and ROBINS-I. The pooled hazard ratio (HR) for each outcome was integrated with a random-effect model. A total of 1 randomized clinical trial and 6 observational studies involving 248,963 patients were included in the systematic review. The meta-analysis of observational studies showed that discontinuation of RAS inhibitors was associated with a higher risk of all-cause mortality (HR, 1.41 [95% CI, 1.23–1.62]; I² = 97%), ESKD (1.32 [95% CI, 1.10–1.57]; I² = 94%) and MACE (1.20 [95% CI 1.15–1.25]; I² = 38%), but not with hyperkalemia (0.79 [95% CI 0.55–1.15]; I² = 90%). Overall risk of bias was moderate-to-serious, and quality of evidence (GRADE system) was low-to-very low. The present study suggests that CKD patients would benefit from continuing RAS inhibitors. [Figure not available: see fulltext.]