Renin-Angiotensin System Inhibitor Discontinuation Before Noncardiac Surgery

Should renin-angiotensin system inhibitors be discontinued before noncardiac surgery?

Discontinuation of renin-angiotensin system inhibitors before noncardiac surgery decreases the risk of intraoperative hypotension and may decrease risk of acute kidney injury, but does not affect risk of mortality or postoperative cardiovascular complications. (Strength of Recommendation: A, meta-analysis of randomized controlled trials [RCTs] and large cohort studies.) An American Heart Association/American College of Cardiology (AHA/ACC) guideline recommends individualized decision-making regarding discontinuation of renin-angiotensin system inhibitors before noncardiac surgery.

A 2025 systematic review and meta-analysis of five RCTs (N = 10,773) evaluated the results of discontinuing vs continuing renin-angiotensin system inhibitors, such as angiotensin-converting enzyme inhibitors and angiotensin receptor blockers, before noncardiac surgery. The trials included adults (mean patient ages 62–72 years; 44% female) who took reninangiotensin system inhibitors for at least 4 weeks preceding noncardiac surgery.¹

Most of the trials excluded patients with uncontrolled hypertension or moderate to severe heart failure. The meta-analysis excluded vascular surgery trials due to concerns that unique technical and physiologic factors associated with vascular surgery would confound results.¹

Patients were randomized to discontinue the reninangiotensin system inhibitors between 12 and 72 hours before surgery or continue the medications on the day of surgery. Adverse outcomes were recorded with varying follow-up duration, ranging from time in postoperative anesthesia care unit to 30 days postoperatively.¹

Discontinuation of renin-angiotensin system inhibitors was associated with a reduction in perioperative hypotension (four trials; n = 7,915; risk ratio = 0.81; 95% CI, 0.73–0.89) and resulted in no difference in perioperative hypertension (four trials; n = 2,696; risk ratio = 1.38; 95% CI, 0.66–2.89) compared with continuing drug treatment. There were no significant differences in rates of acute kidney injury, acute heart failure, myocardial infarction, stroke, or arrhythmias between groups.¹

Authors cited insufficient data to draw conclusions about mortality and expressed uncertainty about conclusions regarding myocardial infarction and stroke due to rare event rates that varied significantly among RCTs. Limitations included bias from nonblinded studies, concerns about deviation from intervention in most studies, and heterogeneity in study protocols.¹

A 2024 systematic review and meta-analysis of 16 studies (N = 59,105; eight RCTs and eight cohort studies) compared the consequences of withholding vs continuing reninangiotensin system inhibitors in adults undergoing noncardiac surgery.² This review included the same RCTs analyzed above, with the addition of vascular surgery RCTs and retrospective cohort studies to provide adequate power for rare outcomes, specifically mortality. The mean patient age ranged from 61 to 72 years, and most patients were male.²

A comparison was made between patients who discontinued renin-angiotensin system inhibitors any time from the morning of surgery to 72 hours prior (n = 27,952) and those who continued medications the day of surgery (n = 31,153). Withholding of the inhibitors was associated with a significantly lower incidence of intraoperative hypotension (11 studies; n = 25,427; odds ratio = 0.49; 95% CI, 0.29–0.83) and acute kidney injury (six studies; n = 22,899; odds ratio = 0.88; 95% CI, 0.82–0.95). Postoperative hypertension was more likely in those who had renin-angiotensin system inhibitors withheld before surgery (seven studies; n = 26,111; odds ratio = 1.65; 95% CI, 1.16–2.34).²