Discontinuation of Renin-Angiotensin System Inhibitors and Clinical Outcomes: A Systematic Review and Meta-Analysis of Randomized Controlled Trial

INTRODUCTION: Renin-angiotensin system inhibitors (RASi) are critical for cardiovascular diseases (CVD), but adverse effects sometimes lead to discontinuation, raising concerns about impacts on major outcomes. Although the observational studies have suggested continuation or restarting of RASi, the evidence from randomized controlled trials (RCTs) and systematic reviews based on RCTs are not sufficient. METHOD: We performed a systematic review and meta-analysis including only RCTs. We searched MEDLINE, EMBASE, CENTRAL, ClinicalTrials.gov, and EU Clinical Trials Register for the full text review analysis. Primary outcomes included all-cause death and CVD events. Risk of bias was assessed using version 2 of the Cochrane Risk of bias tool (RoB2), and the certainty of evidence was evaluated using the Grading of Recommendations Assessment, Development, and Evaluation approach. RESULTS: Among the seven included RCTs (n = 928), three studies (n = 745) reported all-cause mortality and two studies (n = 697) reported CVD events. The meta-analysis did not show difference in all-cause mortality between intervention and control groups (RR 0.95, 95% CI: 0.54 to 1.65, I2 = 0%) and CVD events (RR 1.22, 95% CI: 1.00 to 1.50, I2 = 0%) between intervention and control groups. The certainty of evidence was rated as very low for both outcomes due to RoB, imprecision, and clinical heterogeneity. CONCLUSION: In this systematic review and meta-analysis, there might not be deference in the risk of all-cause mortality or CVD events following RASi discontinuation compared with continuation. The number of enrolled studies was limited, and the certainty of evidence was very low, thus our results should be interpreted carefully.