Legrand M, Falcone J, Cholley B, et al. Continuation vs Discontinuation of Renin-Angiotensin System Inhibitors Before Major Noncardiac Surgery: The Stop-or-Not Randomized Clinical Trial. JAMA. 2024 Sep 24;332(12):970-978. doi: 10.1001/jama.2024.17123.
Abstract

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.

Ratings by Clinicians (at least 3 per Specialty)
Specialty Score
Internal Medicine
Anesthesiology
Surgery - Orthopaedics
Surgery - Neurosurgery
Endocrine
Surgery - General
Cardiology
Surgery - Thoracic
Comments from MORE raters

Anesthesiology rater

This was a well-done trial to answer an important clinical question. The results will not be surprising to most practicing anesthesiologists. The pragmatic clinical approach today is to recommend stopping ACEI/ARBs preop to reduce the risk for intraop hypotension. But if the patient is still taking the medications, we do not cancel the case. We just manage around the issue (e.g. earlier use of vasopressin to support BP intraop). It's nice to see a trial like this one that confirms current clinical practice.

Anesthesiology rater

A well conducted study confirming continuation of angiotensin converting enzyme inhibitors and angiotensin receptor blockers for hypertension until day of surgery results in a small statistically significant increase in hypotension intraoperatively. Appropriate management of hypotension prevents an increase in complications from the hypotension.

Cardiology rater

Overall, a good study that helps answer a common clinical question. Ultimately, no major difference whether the RASI was stopped or not, although more hypotension in the continuation group. The results may not change practice, but are helpful to inform practice.

Endocrine rater

Well done trial providing reassurance that RAS therapy doesn't need to be discontinued for major surgery, but could be considered if there is a concern for intraoperative hypotension.

Endocrine rater

Although no difference in the primary outcome, the 31% increase in hypoglycemic episodes during surgery is something that anesthesiologists need to be aware of.

Internal Medicine rater

A fabulous practical and applicable trial that helps us inform patients on preoperative medication management. Very helpful.

Surgery - Orthopaedics rater

This may be relevant to anaesthetists dealing with orthopaedic patients, although less than 10% of the patients in this trial underwent orthopaedic procedures and most had major abdominal/chest surgery where haemodynamic problems are likely to be more frequent and relevant. An important article for anaesthesia, but not for the orthopaedic surgeon.