Perioperative management of renin-angiotensin system inhibitors in patients undergoing elective major noncardiac surgery: a mixed model investigation using systematic review, meta-analysis, multicentre service evaluation, and national survey

Abstract

Background: The risks and benefits of stopping or continuing renin-angiotensin system (RAS) inhibitors for major noncardiac surgery remain uncertain. We conducted an updated systematic review, national service evaluation, and clinician survey to inform the design of a large clinical trial of perioperative RAS inhibitor use.

Methods: We searched MEDLINE, CINAHL, ProQuest, Cochrane database, Scopus, and Web of Science from January 2000 to October 2024 for randomised controlled trials (RCT) of perioperative RAS inhibitor use. The primary outcome was a composite of mortality and major cardiovascular events (MACE). Secondary outcomes included acute perioperative hypertension and hypotension. Meta-analysis was performed using random effects models. The I² index was used to quantify heterogeneity. We also conducted a prospective clinical service evaluation and clinician survey to describe current clinical practice in UK.

Results: We identified five RCTs (n=2848 patients). Stopping RAS inhibitors was not associated with mortality or MACE (odds ratio [OR] 1.21 [0.60-2.42]; P=0.59; I²=19%). Stopping RAS inhibitors was associated with acute hypertension (OR 1.90 [1.20-3.02]; P=0.007; I²=8%) but fewer hypotension events (OR 0.62 [0.42-0.90]; P=0.01; I²=38%). In a service evaluation of 316 patients in seven hospitals, RAS inhibitors were stopped for 248/316 (79%) patients, with 230/248 (93%) restarting these drugs within 48 h after surgery. In the survey, >80% of clinicians asked patients to stop RAS inhibitors before surgery, for variable reasons concerning risks and benefits.

Conclusions: The optimal approach to perioperative RAS inhibitor use remains uncertain. Although UK clinicians often withhold these drugs, this strategy could cause harm.

Keywords: elective noncardiac surgery; perioperative hypertension; perioperative hypotension; perioperative mortality; renin–angiotensin system inhibitor.