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)

Matthieu Legrand (1, 2, 3, 4, 5) , Emmanuel Futier (6, 7) , Marc Leone (8, 9) , Benjamin Deniau (10, 2, 3) , Alexandre Mebazaa (10, 2, 3, 4, 5) , Benoît Plaud (10, 3, 2) , Pierre Coriat (11) , Patrick Rossignol (12, 13, 5, 4) , Eric Vicaut (10) , Etienne Gayat (10, 3, 2, 4, 5)

1 Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris]
2 UPD7 - Université Paris Diderot - Paris 7
3 MASCOT (UMR_S_942 / U942) - Marqueurs cardiovasculaires en situation de stress
4 Cardiovascular & Renal Clinical Trialists - CRCT - French-Clinical Research Infrastructure Network - F-CRIN [Paris]
5 INI-CRCT - Cardiovascular and Renal Clinical Trialists [Vandoeuvre-les-Nancy]
6 CHU Estaing [Clermont-Ferrand]
7 UCA - Université Clermont Auvergne
8 Service Anesthésie et Réanimation [Hôpital Nord - APHM]
9 MEPHI - Microbes évolution phylogénie et infections
10 Hôpital Lariboisière-Fernand-Widal [APHP]
11 Service d'Anesthésie réanimation [CHU Pitié-Salpêtrière]
12 DCAC - Défaillance Cardiovasculaire Aiguë et Chronique
13 CIC-P - Centre d'investigation clinique plurithématique Pierre Drouin [Nancy]

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.

Keywords: ACE inhibitors; ARB; Strategy; Outcome; Complications; Acute kidney injury; Surgery; Mortality

Domains: Life Sciences [q-bio]; Microbiology and Parasitology; Bacteriology; Life Sciences [q-bio]; Human health and pathology; Cardiology and cardiovascular system; Life Sciences [q-bio]; Human health and pathology; Emerging diseases; Life Sciences [q-bio]; Human health and pathology; Infectious diseases; Life Sciences [q-bio]; Microbiology and Parasitology; Parasitology; Life Sciences [q-bio]; Microbiology and Parasitology; Virology

Matthieu Legrand, Emmanuel Futier, Marc Leone, Benjamin Deniau, Alexandre Mebazaa, et al.. 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). Trials, 2019, 20 (1), pp.160. ⟨10.1186/s13063-019-3247-1⟩. ⟨hal-02262838⟩