Discontinuation of Renin-Angiotensin System Inhibitors and Clinical Outcomes in Chronic Kidney Disease: A Systemic Review and Meta-Analysis

Am J Nephrol. 2023;54(5-6):234-244. doi: 10.1159/000531000. Epub 2023 May 18.

Abstract

Background: Discontinuation of renin-angiotensin system (RAS) inhibitors is common in patients with chronic kidney disease (CKD), and the potential danger has been reported in several studies. However, a comprehensive analysis has not been conducted.

Objectives: This study sought to evaluate the effects of discontinuation of RAS inhibitors in CKD.

Method: Relevant studies up to November 30, 2022, were identified in the PubMed, Embase, Web of Science, and Cochrane Library databases. Efficacy outcomes included the composite of all-cause mortality, cardiovascular events, and end-stage kidney disease (ESKD). Results were combined using a random-effects or fixed-effects model, and sensitivity analysis used the leave-one-out method.

Results: Six observational studies and one randomized clinical trial including 244,979 patients met the inclusion criteria. Pooled data demonstrated that discontinuation of RAS inhibitors was associated with an increased risk of all-cause mortality (HR 1.42, 95% CI 1.23-1.63), cardiovascular event risk (HR 1.25, 95% CI 1.17-1.22), and ESKD (HR 1.23, 95% CI 1.02-1.49). In sensitivity analyses, the risk for ESKD was reduced. Subgroup analysis showed that the risk of mortality was more pronounced in patients with eGFR above 30 mL/min/m2 and in patients with hyperkalemia-related discontinuation. In contrast, patients with eGFR below 30 mL/min/m2 were at great risk of cardiovascular events.

Conclusions: The discontinuation of RAS inhibitors in patients with CKD was associated with a significantly increased risk of all-cause mortality and cardiovascular events. These data suggest that RAS inhibitors should be continued in CKD if the clinical situation allows.

Keywords: Cardiovascular event; Chronic kidney disease; End-stage kidney disease; Meta-analysis; Mortality; Renin-angiotensin system inhibitors.

Publication types

  • Meta-Analysis
  • Systematic Review
  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiotensin-Converting Enzyme Inhibitors / adverse effects
  • Antihypertensive Agents / therapeutic use
  • Cardiovascular Diseases* / chemically induced
  • Cardiovascular Diseases* / etiology
  • Enzyme Inhibitors / pharmacology
  • Humans
  • Kidney Failure, Chronic* / complications
  • Kidney Failure, Chronic* / drug therapy
  • Randomized Controlled Trials as Topic
  • Renal Insufficiency, Chronic* / chemically induced
  • Renal Insufficiency, Chronic* / complications
  • Renal Insufficiency, Chronic* / drug therapy
  • Renin-Angiotensin System

Substances

  • Angiotensin-Converting Enzyme Inhibitors
  • Antihypertensive Agents
  • Enzyme Inhibitors

Grants and funding

This study was supported by the CAMS Innovation Fund for Medical Sciences (2019-I2M-5-046) and The General Program (Key Program, Major Research Plan) of National Natural Science Foundation of China (82070731).