Pause or Keep RAS Inhibitors Before Surgery? Take Your Pick.

LONDON — No blanket statement could be made regarding whether patients undergoing noncardiac surgery should continue or withdraw their renin-angiotensin system (RAS) inhibitor therapy based on the Stop-or-Not Trial.

Death and major complications at 28 days after surgery came out to the same 22% rate between continuation and discontinuation strategies (RR 1.02, 95% CI 0.87-1.19). This lack of difference was consistent across patient subgroups, reported Matthieu Legrand, MD, PhD, of University of California San Francisco, at the European Society of Cardiology (ESC) meeting.

“Both strategies appear to be acceptable,” Legrand concluded from the French trial of over 2,200 people who had been on RAS inhibitors for at least 3 months when they were scheduled for noncardiac surgery from to 2018 to 2023. The full Stop-or-Not data were published simultaneously in JAMA.

“Based on these results, clinicians have greater flexibility in managing [RAS inhibitor] therapy based on individual patient factors and the specifics of the surgery or the patient’s preference,” Legrand said.

According to one estimate, one in four adults having noncardiac surgery are on a RAS inhibitor before surgery.

ESC session discussant Philip Devereaux, MD, PhD, of the Population Health Research Institute in Hamilton, Ontario, Canada, agreed that the results “simplify care” for the majority of patients who “will safely tolerate either receiving or withholding these drugs during the perioperative period.”

Even so, the decision should come down to each individual patient, he suggested.

“Although there was no demonstrated difference between both approaches, perioperative hemodynamics matter after surgery. For patients who have hypotension or hypertension in the preoperative clinic or postoperative setting, I encourage physicians to individualize care regarding the withholding or continuing of perioperative [RAS inhibitors],” Devereaux told the audience.

During a press conference, Legrand predicted that most people will likely continue these medications in the real world — unless they have a high risk of hypotension or bleeding or are scheduled for complex surgery.

He acknowledged that in the Stop-or-Not trial, there was an observed signal of the feared intra-operative hypotension (mean arterial pressure below 60 mm Hg) associated with continuing RAS inhibitors (54% vs 41%, RR 1.31, 95% CI 1.19-1.44).

However, such intra-operative hypotension lasted just 9 versus 6 minutes, and was not enough to translate into more serious complications (e.g., cardiovascular events and acute kidney injury) after surgery, he told the audience.

“The reasons were likely the rapid correction of intraoperative hypertension and the overall short duration of low blood pressure,” Legrand and colleagues wrote. “The rapid correction of intraoperative hypotension in the current trial likely led to a limited between-group difference in the duration of intraoperative hypotension.”

Meanwhile, the worry about discontinuation of RAS inhibitors is that it may possibly lead to its own complications, namely postoperative hypertension, heart failure, and arrhythmia.

Recognizing the dilemma between the continuation and discontinuation strategies, American and European guidelines weakly suggest it is reasonable either way for certain individuals, given the paucity of evidence.

Angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs) make up the RAS inhibitors often prescribed for hypertension and heart failure in clinical practice. In the present report, they were used by 46% and 54% of patients, respectively, at baseline.

Stop-or-Not participants were randomized to continue RAS inhibitor therapy until the day of surgery (n=1,107) or discontinue it 48 hours prior to surgery (n=1,115).

The cohort had a mean age of 67, with 65% men. At baseline, statins were used in over 40% of people and aspirin roughly 35%. The surgeries that were part of the study were one-third abdominal operations, with fewer thoracic (17%) and vascular (12%) surgeries.

The main findings persisted after accounting for missing data and additional adjustment, according to study authors.

They cautioned that the trial assignments were not blinded to patients or anesthesiologists. Furthermore, generalizability may be limited as few patients had chronic heart failure in the trial, and the study was conducted in just one country.

More research is also needed for the perioperative management of RAS inhibitors in heart failure patients with reduced ejection fraction and chronic low blood pressure, Devereaux added.