Continuation vs Discontinuation of Renin-Angiotensin System Inhibitors Before Major Noncardiac Surgery: The Stop-or-Not Randomized Clinical Trial

Matthieu Legrand, Jérémy Falcone, Bernard Cholley, et al

JAMA. Published online August 30, 2024. doi:10.1001/jama.2024.17123

Question  Is a continuation strategy of renin-angiotensin system inhibitors before major noncardiac surgery associated with better postoperative outcomes than discontinuation?

Findings  In this multicenter randomized clinical trial that included 2222 patients, the rate of all-cause mortality and major postoperative complications was 22% in the discontinuation group and 22% in the continuation group (risk ratio, 1.02).

Meaning  In patients undergoing major noncardiac surgery and treated long-term with renin-angiotensin system inhibitors, a continuation strategy of the medication was associated with a similar rate of all-cause mortality and major postoperative complications compared with a discontinuation strategy.

Importance  Before surgery, the best strategy for managing patients who are taking renin-angiotensin system inhibitors (RASIs) (angiotensin-converting enzyme inhibitors or angiotensin receptor blockers) is unknown. The lack of evidence leads to conflicting guidelines.

Objective  To evaluate whether a continuation strategy vs a discontinuation strategy of RASIs before major noncardiac surgery results in decreased complications at 28 days after surgery.

Design, Setting, and Participants  Randomized clinical trial that included patients who were being treated with a RASI for at least 3 months and were scheduled to undergo a major noncardiac surgery between January 2018 and April 2023 at 40 hospitals in France.

Intervention  Patients were randomized to continue use of RASIs (n = 1107) until the day of surgery or to discontinue use of RASIs 48 hours prior to surgery (ie, they would take the last dose 3 days before surgery) (n = 1115).

Main Outcomes and Measures  The primary outcome was a composite of all-cause mortality and major postoperative complications within 28 days after surgery. The key secondary outcomes were episodes of hypotension during surgery, acute kidney injury, postoperative organ failure, and length of stay in the hospital and intensive care unit during the 28 days after surgery.

Results  Of the 2222 patients (mean age, 67 years [SD, 10 years]; 65% were male), 46% were being treated with angiotensin-converting enzyme inhibitors at baseline and 54% were being treated with angiotensin receptor blockers. The rate of all-cause mortality and major postoperative complications was 22% (245 of 1115 patients) in the RASI discontinuation group and 22% (247 of 1107 patients) in the RASI continuation group (risk ratio, 1.02 [95% CI, 0.87-1.19]; P = .85). Episodes of hypotension during surgery occurred in 41% of the patients in the RASI discontinuation group and in 54% of the patients in the RASI continuation group (risk ratio, 1.31 [95% CI, 1.19-1.44]). There were no other differences in the trial outcomes.

Conclusions and Relevance  Among patients who underwent major noncardiac surgery, a continuation strategy of RASIs before surgery was not associated with a higher rate of postoperative complications than a discontinuation strategy.

Trial Registration  ClinicalTrials.gov Identifier: NCT03374449

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