STOP-or-NOT: No Benefit to Discontinuing RASi Prior to Major Surgery

The landmark STOP or NOT trial, which assessed discontinuation of a renin-angiotensin system inhibitor (RASi) before noncardiac surgery, has come to the following conclusion: continuation or discontinuation of RASi should be based on individual patient needs.

Presented at the European Society of Cardiology (ESC) Congress 2024, results of the trial indicate both strategies lead to similar rates of major postoperative complications, with investigators noting rates of hypotension during noncardiac surgery were greater and longer in the continuation group, but this increase did not contribute to a greater risk of postoperative complications.

“Due to a lack of conclusive data from randomized trials, whether to stop RASIs before non-cardiac surgery is uncertain. RASI continuation might lead to intra-operative hypotension, which could result in post-operative cardiovascular events and acute kidney injury. On the other hand, RASI discontinuation might cause post-operative hypertension, heart failure or arrhythmias,” explained principal investigator Matthieu Legrand MD, PhD, professor and director of Clinical research in the department of Anesthesiology and Perioperative medicine of the University of California San Francisco. “The STOP-or-NOT trial was conducted to clear up uncertainties and we showed no differences in major post-operative outcomes between stopping or not stopping RASIs.”

Citing the lack of conclusive evidence related to the management of patients using RASi before undergoing noncardiac surgery, the STOP-or-NOT trial was designed as an open-label, randomized controlled trial conducted among patients scheduled for elective major non-cardiac surgery who were chronically treated with ACE inhibitors or ARBs for at least 3 months before surgery. Conducted at 40 sites across France, the trial recruited 2222 patients, with 1115 randomized to RASi discontinuation and 1107 randomized to continuation.

The overall cohort had a mean age of 67 years, 65% were male, 98% were treated for hypertension, 9% had chronic kidney disease, 8% had diabetes, and 4% had heart failure. Among the cohort, 54% were treated with ARBs at baseline and 46% were treated with ACE inhibitors.

Per trial protocol, patients were randomized in a 1:1 ratio to continue RASi until the day of surgery or to discontinue them 48 hours prior. Investigators noted both groups received recommendations to resume RASi treatment as soon as possible after surgery when the oral route was deemed feasible.

The primary outcome of interest for the study was a composite of all-cause mortality and major post-operative complications within 28 days after surgery. Investigators pointed out major postoperative complications included major cardiovascular events, sepsis or septic shock, respiratory complications, unplanned intensive care unit (ICU) admission or readmission, acute kidney injury (AKI), hyperkalemia, or need for surgical reintervention. Secondary outcomes of interest for the trial included hypotension during surgery, all-cause mortality, episodes of AKI, post-operative organ failure, and hospital and ICU length of stay during the 28 days after surgery.

Primary outcome analyses demonstrated comparable rates of all-cause and major postoperative complications, with such an event occurring among 22% of patients in both groups. (Risk ratio [RR], 1.02; 95% Confidence Interval [CI], 0.87 to 1.19; P =.85). Secondary outcome analyses revealed hypotension episodes during surgery occurred among 41% of the discontinuation group and 54% of the continuation group (RR, 1.31; 95% CI, 1.19 to 1.44).

Investigators noted the median duration of hypotension with a mean arterial pressure below 60 mmHg was 6 (interquartile range [IQR], 4 to 12) minutes among the discontinuation group and 9 (IQR, 5 to 16) minutes among the continuation group (mean difference of 3.7 minutes; 95% CI, 1.4 to 6.0). Investigators highlighted there were no other differences in trial outcomes.

“Results from the STOP-or-NOT trial may now be used within guideline recommendations, which are generally weak. Given the lack of difference, both strategies appear acceptable, indicating that a tailored approach to RASI continuation could be used. A discontinuation strategy may be considered if there is a particular concern for hypotension, while continuation may be preferred in patients who are worried about stopping their medication or for practical purposes,” Legrand added.