A large randomized clinical trial, the Stop-or-Not trial, has found that neither continuing nor discontinuing renin-angiotensin system (RAS) inhibitors before noncardiac surgery demonstrates a clear advantage in patient outcomes. The study, involving over 2,200 patients, showed similar rates of death and major complications at 28 days post-surgery, regardless of whether patients continued or stopped their RAS inhibitor therapy.
The findings, presented at the European Society of Cardiology (ESC) meeting and published in JAMA, suggest that clinicians have flexibility in managing RAS inhibitor therapy based on individual patient factors and surgical specifics. According to estimates, one in four adults undergoing noncardiac surgery are on a RAS inhibitor prior to their procedure.
Key Findings from the Stop-or-Not Trial
Matthieu Legrand, MD, PhD, of University of California San Francisco, reported that the rate of death and major complications at 28 days post-surgery was 22% in both the continuation and discontinuation groups (RR 1.02, 95% CI 0.87-1.19). This consistency was observed across various patient subgroups.
Philip Devereaux, MD, PhD, of the Population Health Research Institute in Hamilton, Ontario, Canada, commented that the results "simplify care" for most patients, who "will safely tolerate either receiving or withholding these drugs during the perioperative period."
Intra-operative Hypotension
The trial did reveal a higher incidence of intra-operative hypotension (mean arterial pressure below 60 mm Hg) in patients who continued RAS inhibitors (54% vs 41%, RR 1.31, 95% CI 1.19-1.44). However, this did not translate into a higher rate of serious complications such as cardiovascular events or acute kidney injury.
Legrand explained that the rapid correction of intraoperative hypotension likely limited the impact on more serious complications. The duration of hypotension was also short, lasting just 9 minutes in the continuation group versus 6 minutes in the discontinuation group.
Individualized Patient Care
Despite the overall lack of difference between the two strategies, experts emphasize the importance of individualized patient care. Devereaux advised physicians to consider perioperative hemodynamics and individual patient risk factors when deciding whether to continue or withhold RAS inhibitors.
Legrand predicted that most patients would likely continue these medications unless they have a high risk of hypotension or bleeding or are scheduled for complex surgery.
Current Guidelines and Future Research
Existing American and European guidelines offer weak recommendations for either continuation or discontinuation of RAS inhibitors, reflecting the limited evidence available. The Stop-or-Not trial provides valuable data to inform clinical decision-making.
The study authors noted several limitations, including the lack of blinding and the limited number of patients with chronic heart failure. Further research is needed to optimize the perioperative management of RAS inhibitors, particularly in heart failure patients with reduced ejection fraction and chronic low blood pressure.
Angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs) are the primary RAS inhibitors, used by 46% and 54% of patients respectively in the study. Participants were randomized to either 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.
