PeriOperative ISchemic Evaluation-2 Trial

Summary

Major surgeries not involving the heart are common, and major heart problems during or after such surgeries represent a large population health problem. Few treatments to prevent heart problems around the time of surgery have been tested. There is encouraging data suggesting that small doses of Acetyl-Salicylic Acid (ASA) and Clonidine, which are two medications, given individually for a short period before and after major surgeries may prevent major heart problems. The POISE-2 Trial is a large international study to test if ASA and Clonidine can prevent heart attacks and deaths from heart problems around the time of surgery.

Timeline

Start

2010-07

Primary completion

2014-03

Completion

2015-01

Outcome

Missed primary endpoint

paper had no significant effect on the rate of a composite of death or nonfatal myocardial infarction PMID 24679062 ↗

paper hazard ratio in the aspirin group, 0.99; 95% confidence interval [CI], 0.86 to 1.15; P=0.92). PMID 24679062 ↗

paper Clonidine, as compared with placebo, did not reduce the number of primary-outcome events (367 and 339, respectively PMID 24679061 ↗

paper did not reduce the rate of the composite outcome of death or nonfatal myocardial infarction PMID 24679061 ↗

Publications

• Results Devereaux PJ, Mrkobrada M, Sessler DI, Leslie K, Alonso-Coello P, Kurz A, Villar JC, Sigamani A, Biccard BM, Meyhoff CS, Parlow JL, Guyatt G, Robinson A, Garg AX, Rodseth RN, Botto F, Lurati Buse G, Xavier D, Chan MT, Tiboni M, Cook D, Kumar PA, Forget P, Malaga G, Fleischmann E, Amir M, Eikelboom J, Mizera R, Torres D, Wang CY, VanHelder T, Paniagua P, Berwanger O, Srinathan S, Graham M, Pasin L, Le Manach Y, Gao P, Pogue J, Whitlock R, Lamy A, Kearon C, Baigent C, Chow C, Pettit S, Chrolavicius S, Yusuf S; POISE-2 Investigators. Aspirin in patients undergoing noncardiac surgery. N Engl J Med. 2014 Apr 17;370(16):1494-503. doi: 10.1056/NEJMoa1401105. Epub 2014 Mar 31.
• Results Devereaux PJ, Sessler DI, Leslie K, Kurz A, Mrkobrada M, Alonso-Coello P, Villar JC, Sigamani A, Biccard BM, Meyhoff CS, Parlow JL, Guyatt G, Robinson A, Garg AX, Rodseth RN, Botto F, Lurati Buse G, Xavier D, Chan MT, Tiboni M, Cook D, Kumar PA, Forget P, Malaga G, Fleischmann E, Amir M, Eikelboom J, Mizera R, Torres D, Wang CY, Vanhelder T, Paniagua P, Berwanger O, Srinathan S, Graham M, Pasin L, Le Manach Y, Gao P, Pogue J, Whitlock R, Lamy A, Kearon C, Chow C, Pettit S, Chrolavicius S, Yusuf S; POISE-2 Investigators. Clonidine in patients undergoing noncardiac surgery. N Engl J Med. 2014 Apr 17;370(16):1504-13. doi: 10.1056/NEJMoa1401106. Epub 2014 Mar 31.
• Results Garg AX, Kurz A, Sessler DI, Cuerden M, Robinson A, Mrkobrada M, Parikh C, Mizera R, Jones PM, Tiboni M, Rodriguez RG, Popova E, Rojas Gomez MF, Meyhoff CS, Vanhelder T, Chan MT, Torres D, Parlow J, de Nadal Clanchet M, Amir M, Bidgoli SJ, Pasin L, Martinsen K, Malaga G, Myles P, Acedillo R, Roshanov P, Walsh M, Dresser G, Kumar P, Fleischmann E, Villar JC, Painter T, Biccard B, Bergese S, Srinathan S, Cata JP, Chan V, Mehra B, Leslie K, Whitlock R, Devereaux PJ; POISE-2 Investigators. Aspirin and clonidine in non-cardiac surgery: acute kidney injury substudy protocol of the Perioperative Ischaemic Evaluation (POISE) 2 randomised controlled trial. BMJ Open. 2014 Feb 25;4(2):e004886. doi: 10.1136/bmjopen-2014-004886.
• Roshanov PS, Walsh MW, Garg AX, Cuerden M, Lam NN, Hildebrand AM, Lee VW, Mrkobrada M, Leslie K, Chan MTV, Borges FK, Wang CY, Xavier D, Sessler DI, Szczeklik W, Meyhoff CS, Srinathan SK, Sigamani A, Villar JC, Chow CK, Polanczyk CA, Patel A, Harrison TG, Fielding-Singh V, Cata JP, Parlow J, de Nadal M, Devereaux PJ. Preoperative estimated glomerular filtration rate to predict cardiac events in major noncardiac surgery: a secondary analysis of two large international studies. Br J Anaesth. 2025 Feb;134(2):297-307. doi: 10.1016/j.bja.2024.10.039. Epub 2025 Jan 2.
• Turan A, Rivas E, Devereaux PJ, Pu X, Rodriguez-Patarroyo FA, Yalcin EK, Nault R, Maheshwari K, Ruetzler K, Sessler DI. Relative contributions of anaemia and hypotension to myocardial infarction and renal injury: Post hoc analysis of the POISE-2 trial. Eur J Anaesthesiol. 2023 May 1;40(5):365-371. doi: 10.1097/EJA.0000000000001816. Epub 2023 Mar 9.
• Natale P, Palmer SC, Saglimbene VM, Ruospo M, Razavian M, Craig JC, Jardine MJ, Webster AC, Strippoli GF. Antiplatelet agents for chronic kidney disease. Cochrane Database Syst Rev. 2022 Feb 28;2(2):CD008834. doi: 10.1002/14651858.CD008834.pub4.
• Biccard BM, Sigamani A, Chan MTV, Sessler DI, Kurz A, Tittley JG, Rapanos T, Harlock J, Szalay D, Tiboni ME, Popova E, Vasquez SM, Kabon B, Amir M, Mrkobrada M, Mehra BR, El Beheiry H, Mata E, Tena B, Sabate S, Zainal Abidin MK, Shah VR, Balasubramanian K, Devereaux PJ. Effect of aspirin in vascular surgery in patients from a randomized clinical trial (POISE-2). Br J Surg. 2018 Nov;105(12):1591-1597. doi: 10.1002/bjs.10925. Epub 2018 Jul 18.
• Graham MM, Sessler DI, Parlow JL, Biccard BM, Guyatt G, Leslie K, Chan MTV, Meyhoff CS, Xavier D, Sigamani A, Kumar PA, Mrkobrada M, Cook DJ, Tandon V, Alvarez-Garcia J, Villar JC, Painter TW, Landoni G, Fleischmann E, Lamy A, Whitlock R, Le Manach Y, Aphang-Lam M, Cata JP, Gao P, Terblanche NCS, Ramana PV, Jamieson KA, Bessissow A, Mendoza GR, Ramirez S, Diemunsch PA, Yusuf S, Devereaux PJ. Aspirin in Patients With Previous Percutaneous Coronary Intervention Undergoing Noncardiac Surgery. Ann Intern Med. 2018 Feb 20;168(4):237-244. doi: 10.7326/M17-2341. Epub 2017 Nov 14.
• Garg AX, Kurz A, Sessler DI, Cuerden M, Robinson A, Mrkobrada M, Parikh CR, Mizera R, Jones PM, Tiboni M, Font A, Cegarra V, Gomez MF, Meyhoff CS, VanHelder T, Chan MT, Torres D, Parlow J, Clanchet Mde N, Amir M, Bidgoli SJ, Pasin L, Martinsen K, Malaga G, Myles P, Acedillo R, Roshanov PS, Walsh M, Dresser G, Kumar P, Fleischmann E, Villar JC, Painter T, Biccard B, Bergese S, Srinathan S, Cata JP, Chan V, Mehra B, Wijeysundera DN, Leslie K, Forget P, Whitlock R, Yusuf S, Devereaux PJ; POISE-2 Investigators. Perioperative aspirin and clonidine and risk of acute kidney injury: a randomized clinical trial. JAMA. 2014 Dec 3;312(21):2254-64. doi: 10.1001/jama.2014.15284.
• Devereaux PJ; POISE-2 Investigators. Rationale and design of the PeriOperative ISchemic Evaluation-2 (POISE-2) trial: an international 2 x 2 factorial randomized controlled trial of acetyl-salicylic acid vs. placebo and clonidine vs. placebo in patients undergoing noncardiac surgery. Am Heart J. 2014 Jun;167(6):804-9.e4. doi: 10.1016/j.ahj.2014.01.007. Epub 2014 Feb 22.
• Chludzinski A, Irani C, Mascha EJ, Kurz A, Devereaux PJ, Sessler DI. Protocol understanding and anxiety in perioperative clinical trial patients approached for consent on the day of surgery. Mayo Clin Proc. 2013 May;88(5):446-54. doi: 10.1016/j.mayocp.2012.12.014.

Drugs

Evaluation	Drug	Modality	Dose	Route
Subject	Aspirin	Small molecule	100 mg	Oral
Subject	Clonidine	Other / unclassified	0.2 mg	Oral

Indications