Should renin-angiotensin system inhibitors be discontinued before surgery?

Many patients who undergo major surgery have a history of hypertension, diabetes or heart failure, and are often receiving long-term treatment with a renin-angiotensin system inhibitor (i.e., angiotensin-converting enzyme inhibitor [ACEI] or angiotensin receptor blocker [ARB]). The best strategy for managing these medications before major surgery is unknown, and there is little evidence from randomized clinical trials to enable establishment of recommendations. The continuation of these agents might lead to intraoperative hypotension, which has been associated with postoperative complications, including cardiovascular events and acute kidney injury. However, their discontinuation might lead to complications, including postoperative hypertension, heart failure and arrhythmia. To examine this issue, a new study (the Stop-or-Not trial) evaluated whether a continuation strategy versus a discontinuation strategy of renin-angiotensin system inhibitors before major noncardiac surgery results in decreased all-cause mortality and postoperative complications within 28 days post-surgery.The randomized clinical trial included patients who had been receiving an ACEI or ARB for at least three months and who were scheduled to undergo a major noncardiac surgery at one of 40 hospitals in France. Patients were randomized to continue use of the ACEI/ARB (n=1,107) until the day of surgery or to discontinue the ACEI/ARB 48 hours prior to surgery (n=1,115; patients were instructed to take the last dose 3 days before surgery).The primary outcome was a composite of all-cause mortality and major postoperative complications within 28 days after surgery. 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-day-period after surgery.Results showed the following:The study included 2,222 patients (mean age, 67 years; 65% male).At baseline, 46% of patients were being treated with an ACEI and 54% with an ARB. The rate of all-cause mortality and major postoperative complications was 22% (245 of 1,115 patients) in the renin-angiotensin system inhibitor discontinuation group and 22% (247 of 1,107 patients) in the renin-angiotensin system inhibitor continuation group (risk ratio, 1.02 [95% CI, 0.87–1.19]; p=0.85). Episodes of hypotension during surgery occurred in 41% of the patients in the renin-angiotensin system inhibitor discontinuation group and in 54% of the patients in the renin-angiotensin system inhibitor continuation group (risk ratio, 1.31 [95% CI, 1.19–1.44]). There were no other differences in the trial outcomes.The investigators conclude that among patients who underwent major noncardiac surgery, a continuation strategy of renin-angiotensin system inhibitors before surgery was not associated with a higher rate of all-cause mortality or major postoperative complications compared with a discontinuation strategy. The authors comment that the higher incidence of intraoperative hypotension in the renin-angiotensin system inhibitor continuation group did not translate into a higher risk of all-cause mortality or major postoperative complications. The reason was likely the rapid correction of intraoperative hypotension (using vasopressors) in the study, leading to an overall short duration of low blood pressure and a limited between-group difference in the duration of intraoperative hypotension. Whether this difference would remain small in more resource-constrained settings (e.g., with limited availability of intraoperative vasopressors) is uncertain.The authors believe that the results of this trial could have an effect on future guidelines. The absence of a difference in postoperative outcomes makes both strategies (continuation and discontinuation) acceptable and safe. However, they caution that a renin-angiotensin system inhibitor discontinuation strategy may be considered if there is a particular concern for profound hypotension, due to the potentially increased risk of intraoperative hypotension with renin-angiotensin system inhibitor continuation.Reference:Legrand M, Falcone J, Cholley B, et al; Stop-or-Not Trial Group. Continuation vs discontinuation of renin-angiotensin system inhibitors before major noncardiac surgery. The Stop-or-Not Randomized Clinical Trial. JAMA 2024. Published online August 30, 2024. (accessed September 5, 2024).

Should renin-angiotensin system inhibitors be discontinued before surgery?

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