NCT03374449: STOPORNOT

Impact of Renin-Angiotensin System Inhibitors Continuation on Outcome After Major Surgery

Completed NA Last updated 22 May 2024

What this trial tests

NA trial testing continuation of the RAS-inhibitors in Renin Angiotensin System in 2,222 participants. Completed in 24 December 2023.

Timeline

6 February 2018

Primary endpoint
24 December 2023

24 December 2023

Quick facts

Lead sponsor	Assistance Publique - Hôpitaux de Paris
Phase	NA
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	none
Primary purpose	other
Enrollment	2,222
Start date	6 February 2018
Primary completion	24 December 2023
Estimated completion	24 December 2023
Sites	1 location across France

Drugs / interventions tested

• continuation of the RAS-inhibitors
• discontinuation of the RAS-inhibitors

Conditions studied

• Renin Angiotensin System — all drugs for Renin Angiotensin System →
• Surgery — all drugs for Surgery →

Sponsor

Assistance Publique - Hôpitaux de Paris — full company profile →

Who can join

Adults 18 to 99, any sex, with Renin Angiotensin System or Surgery. Patients with the condition only — healthy volunteers not accepted.

Sponsor's own description

More than 200 million major surgical procedures are performed annually worldwide. Many of these patients have comorbidities including hypertension and/or heart failure. Chronic treatment of hypertension and/or heart failure very often includes a Renin-Angiotensin System (RAS) inhibitor (Angiotensin-Converting Enzyme Inhibitors (ACE-Is) or Angiotensin Receptor Blockers (ARBs). To stop or not to stop these medications before major surgery remain unknown. Data on management of RAS inhibitors before major surgery and anesthesia remain lacking and matter of debate. It is much likely that the strategy regarding management of RAS inhibitors in the peri-operative setting have important impact on peri-operative complications.

The lack of evidence leads to conflicting guidelines with respect to RAS inhibitors management before major surgery. While French guidelines are to stop RAS inhibitors patients with hypertension to avoid profound anesthestic-drugs-induced hypotension, international guidelines differ. The American heart association task force states that continuation of RAS inhibitors perioperatively is reasonable (class IIa recommendation,level of evidence: B). The purpose of this study is to determine the prognostic impact of withholding vs continuing ARBs before major non cardiac surgery.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. Continuation vs Discontinuation of Renin-Angiotensin System Inhibitors Before Major Noncardiac Surgery: The Stop-or-Not Randomized Clinical Trial.
   Legrand M, Falcone J, Cholley B, Charbonneau H, et al · · 2024 · cited 52× · PMID 39212270 · DOI 10.1001/jama.2024.17123
2. 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).
   Legrand M, Futier E, Leone M, Deniau B, et al · · 2019 · cited 24× · PMID 30836981 · DOI 10.1186/s13063-019-3247-1
3. New pharmacological agents and novel cardiovascular pharmacotherapy strategies in 2024.
   Tamargo J, Agewall S, Ambrosio G, Borghi C, et al · · 2025 · cited 6× · PMID 40058879 · DOI 10.1093/ehjcvp/pvaf012
4. Perioperative myocardial injury and infarction after noncardiac surgery: a review of pathophysiology, diagnosis, and management.
   Kashlan B, Kinno M, Syed M. · · 2024 · cited 6× · PMID 38343871 · DOI 10.3389/fcvm.2024.1323425
5. Preoperative Cardiovascular Risk and Postoperative Outcomes by Renin-Angiotensin System Inhibitor Use: A Secondary Analysis of a Randomized Clinical Trial.
   Tang J, Pirracchio R, Cholley B, Joosten A, et al · · 2025 · cited 3× · PMID 40560582 · DOI 10.1001/jamacardio.2025.1920
6. Impact of continuing renin-angiotensin-aldosterone system inhibitors before surgery on intraoperative hypotensive events: a secondary analysis of the STOP-or-NOT Trial.
   Pirracchio R, Cholley B, Falcone J, Charbonneau H, et al · · 2026 · PMID 41513520 · DOI 10.1016/j.bja.2025.11.049
7. Perioperative antihypertensive medications and effects on functional decline and mortality in non-cardiac surgery.
   Suzukawa R, Mandai S, Nakano Y, Inaba S, et al · · 2025 · PMID 40896736 · DOI 10.1093/ehjopen/oeaf096
8. Severe refractory hypotension during induction of general anesthesia in patient after 48 hours of azilsartan discontinuation: A case report.
   Lee JH, Kim YY, Heo HJ, Kim G, et al · · 2023 · PMID 38013296 · DOI 10.1097/md.0000000000036126