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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.
Multicenter, prospective, randomized, pragmatic, parallel-group clinical trial. The inclusion visit takes place between 4 months and no later than 3 days before the surgery visit.
Five follow-up visits are planned
End of research visit is the 28 days+15 days (43 days maximum) follow-up visit.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| continuation of the RAS-inhibitors | Experimental | in the continuation of the RAS-inhibitors arm the treatment will be continued until the morning the day of surgery. |
|
| discontinuation of the RAS-inhibitors | Active Comparator | In this arm : discontinuation of the RAS-inhibitors 48 hours before surgery Patients won't receive the drug on the morning of the day of the surgery. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| continuation of the RAS-inhibitors | Procedure | drug intake |
| |
| Measure | Description | Time Frame |
|---|---|---|
| composite outcome composed of all-cause mortality and major postoperative complications within 28 days after surgery. | Complications will be validated by an adjudication committee, blinded to the treatment arm. Death; Acute Myocardial infarction; Arterial or venous thrombosis; Stroke; Acute pulmonary oedema; Post-operative cardiogenic shock; Acute severe hypertension crisis; Cardiac arrhythmia requiring therapeutic intervention; Postoperative episodes of sepsis; Postoperative respiratory complication; Need for unplanned intensive care unit admission or readmission; Acute kidney injury: KDIGO criteria Baseline serum creatinine is obtained from the pre-operative blood sample; Surgical complications: need for reoperation for any reason and radiologic interventions for abscess drainage; Severe Hyperkalemia: serum potassium level >5.5 mmol/L and requiring therapeutic intervention (insulin/glucose infusion and/or sodium bicarbonate infusion and/or intravenous B2 agonists and/or intravenous calcium gluconate and/or renal replacement therapy and/or ventricular tachycardia or ventricular fibrillation). | after surgery until day 28 |
| Measure | Description | Time Frame |
|---|---|---|
| Episodes of hypotension | Episodes requiring vasopressors administration | during anesthesia and surgery |
| Acute kidney injury | according to the KDIGO criteria |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Eienne Gayat, MD, PhD | Hospital Laribioisière, APHP | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Hospital Lariboisiere | Paris | 75010 | France |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 23558177 | Background | Legrand M, Payen D. Case scenario: Hemodynamic management of postoperative acute kidney injury. Anesthesiology. 2013 Jun;118(6):1446-54. doi: 10.1097/ALN.0b013e3182923e8a. No abstract available. | |
| 18375316 | Background | Augoustides JG. Angiotensin blockade and general anesthesia: so little known, so far to go. J Cardiothorac Vasc Anesth. 2008 Apr;22(2):177-9. doi: 10.1053/j.jvca.2008.01.002. No abstract available. |
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The aim of this study is to evaluate the impact of Renin-Angiotensin System inhibitors management (Continuation or discontinuation 48 hours before surgery) on outcome in patients undergoing scheduled major non-cardiac surgery (surgery with an expected duration of more than 2 hours from the surgical incision and a post-operative hospital stay of least 3 days)
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Endpoint validated by an adjudication commitee blinded to the arm.
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| discontinuation of the RAS-inhibitors |
| Procedure |
no drug intake |
|
| after surgery until day 28 |
| Maximum SOFA score | patients admitted to ICU | from postoperative day 1 to day 7 |
| Duration of hospital stay | Patients who will be outside the hospital but in other types of health care facilities at day 28 will be considered to have been discharged home | after surgery until day 28 |
| Hospital free-days | Duration after hospital discharge | censored at 28 days following surgery |
| 25988640 | Background | Mets B. To stop or not? Anesth Analg. 2015 Jun;120(6):1413-9. doi: 10.1213/ANE.0000000000000758. No abstract available. |
| 25329033 | Background | Mets B, Hennrikus E. Perioperative angiotensin axis blockade, to continue or discontinue, that is the question? Anesth Analg. 2014 Nov;119(5):1223-4. doi: 10.1213/ANE.0000000000000430. No abstract available. |
| 25091544 | Background | Fleisher LA, Fleischmann KE, Auerbach AD, Barnason SA, Beckman JA, Bozkurt B, Davila-Roman VG, Gerhard-Herman MD, Holly TA, Kane GC, Marine JE, Nelson MT, Spencer CC, Thompson A, Ting HH, Uretsky BF, Wijeysundera DN; American College of Cardiology; American Heart Association. 2014 ACC/AHA guideline on perioperative cardiovascular evaluation and management of patients undergoing noncardiac surgery: a report of the American College of Cardiology/American Heart Association Task Force on practice guidelines. J Am Coll Cardiol. 2014 Dec 9;64(22):e77-137. doi: 10.1016/j.jacc.2014.07.944. Epub 2014 Aug 1. No abstract available. |
| 41513520 | Derived | Pirracchio R, Cholley B, Falcone J, Charbonneau H, Delaporte A, Lemoine A, Joosten A, Gayat E, Legrand M; STOP-or-NOT trial group. Impact of continuing renin-angiotensin-aldosterone system inhibitors before surgery on intraoperative hypotensive events: a secondary analysis of the STOP-or-NOT Trial. Br J Anaesth. 2026 Mar;136(3):897-905. doi: 10.1016/j.bja.2025.11.049. Epub 2026 Jan 9. |
| 40560582 | Derived | Tang J, Pirracchio R, Cholley B, Joosten A, Birckener J, Falcone J, Charbonneau H, Delaporte A, Chen D, Gayat E, Legrand M. Preoperative Cardiovascular Risk and Postoperative Outcomes by Renin-Angiotensin System Inhibitor Use: A Secondary Analysis of a Randomized Clinical Trial. JAMA Cardiol. 2025 Sep 1;10(9):942-948. doi: 10.1001/jamacardio.2025.1920. |
| 39212270 | Derived | Legrand M, Falcone J, Cholley B, Charbonneau H, Delaporte A, Lemoine A, Garot M, Joosten A, Meistelman C, Cheron-Leroy D, Rives JP, Pastene B, Dewitte A, Sigaut S, Danguy des Deserts M, Truc C, Boisson M, Lasocki S, Cuvillon P, Schiff U, Jaber S, Le Guen M, Caillard A, Bar S, Pereira de Souza Neto E, Colas V, Dimache F, Girardot T, Jozefowicz E, Viquesnel S, Berthier F, Vicaut E, Gayat E; 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 Sep 24;332(12):970-978. doi: 10.1001/jama.2024.17123. |
| 30836981 | Derived | Legrand M, Futier E, Leone M, Deniau B, Mebazaa A, Plaud B, Coriat P, Rossignol P, Vicaut E, Gayat E; STOP-OR-NOT study investigators. 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 Mar 5;20(1):160. doi: 10.1186/s13063-019-3247-1. |