Impact of renin-angiotensin system inhibitors continuation versus discontinuation on outcome after major surgery: protocol of a multicenter randomized, controlled trial (STOP-or-NOT trial)

Abstract

Background Chronic treatment of hypertension or heart failure very often includes an angiotensin-converting enzyme inhibitors (ACE-Is) or angiotensin receptor blockers (ARBs) as renin-angiotensin system inhibitors (RASi) treatments. To stop or not to stop these medications before major surgery remains an unresolved issue. The lack of evidence leads to conflicting guidelines with respect to RASi management before major surgery. The purpose of this study is to evaluate the impact of a strategy of RASi continuation or discontinuation on perioperative complications in patients undergoing major non-cardiac surgery. Methods This is a multicenter, open-labeled randomized controlled trial in > 30 French centers. In the experimental group, RASi will be continued while the treatment will be stopped 48 h before the surgery in the control arm. The primary endpoint is a composite endpoint of major complications after surgery. An endpoint adjudication committee will review clinical data and adjudicate efficacy endpoints while blinded to the assigned study drug group. Main analysis will be by intention-to-treat comparing the composite outcome measure at 28 days in the two groups. A total of 2222 patients are planned to detect an absolute complications difference of 5%. Discussion The results of the trial should provide robust evidence to anesthesiologists and surgeons regarding management of RASi before major non-cardiac surgery. Trial registration ClinicalTrials.gov, NCT03374449 . Registered on 11 December 2017. Electronic supplementary material The online version of this article (10.1186/s13063-019-3247-1) contains supplementary material, which is available to authorized users.

The effect of continuing versus withholding angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers on mortality and major adverse cardiovascular events in hypertensive patients undergoing elective non-cardiac surgery: study protocol for a multi-centric open-label randomised controlled trial

“…Based on an incidence of 25% of the primary endpoint in the reference group [ 11 ], a total of 2016 patients will allow an 80% power to detect a 21% relative decrease of complications in the experimental group. To account for dropouts, a total of 2100 patients (700 at each centre) will be included.…”

Cardiovascular Consequences of Acute Kidney Injury

“…64 Yet it remains largely unknown whether withholding or continuing these treatments before major surgery influences the outcome, and the effects are currently being investigated. 80 Follow-up by a nephrologist after an episode of acute kidney injury has been associated with reduced all-cause mortality (hazard ratio, 0.76; 95% CI, 0.62 to 0.93). 81 Strikingly, however, only a minority of at-risk survivors of acute kidney injury are referred to a nephrologist for ongoing care.…”

Improving Postoperative Acute Kidney Injury Rates Following Primary Total Joint Arthroplasty

“…the literature as to whether ACEi/ARBs should be stopped preoperatively to minimize perioperative complication; however, we elected to be more restrictive with ACEi/ARB use both preoperatively and postoperatively given the nature of our protocol [37,38]. Randomized trials are ongoing to hopefully establish better guidelines on the perioperative use of ACEi/ARBs in the future [39,40]. Additionally, to further promote a more euvolemic patient preoperatively, patients were allowed to continue preoperative clear fluid intake up to within 4 hours of their planned operative time [41,42].…”