One-year Results of a Factorial Randomized Trial of Aspirin versus Placebo and Clonidine versus Placebo in Patients Having Noncardiac Surgery

Sessler DI 1 , Conen D , Leslie K , Yusuf S , Popova E , Graham M Show all authors , Kurz A , Villar JC , Mrkobrada M , Sigamani A , Biccard BM , Meyhoff CS , Parlow JL , Guyatt G , Xavier D , Chan MTV , Kumar PA , Forget P , Malaga G , Fleischmann E , Amir M , Torres D , Wang CY , Paniagua P , Berwanger O , Srinathan S , Landoni G , Manach YL , Whitlock R , Lamy A , Balasubramanian K , Gilron I , Turan A , Pettit S , Devereaux PJ , Perioperative Ischemic Evaluation-2 Trial (POISE-2) Investigators

Affiliations 

  • 1 From the Department of Outcomes Research, Anesthesiology Institute, Cleveland Clinic, Cleveland, Ohio (D.I.S., A.K., A.T.) Population Health Research Institute (D.I.S., D.C., S.Y., Y.L.M., A.L., K.B., S.P., P.J.D.) Department of Medicine (D.C., S.Y., G.G., P.J.D.) Department of Health Research Methods, Evidence, and Impact (D.C., S.Y., G.G., Y.L.M., A.L., P.J.D.) Faculty of Health Sciences, Department of Anesthesia (Y.L.M.) Department of Surgery (R.W., A.L.), McMaster University, Hamilton, Ontario, Canada Department of Anaesthesia and Pain Management, Royal Melbourne Hospital and Centre for Integrated Critical Care, University of Melbourne, Melbourne, Australia (K.L.) Public Health and Clinical Epidemiology-Iberoamerican Cochrane Centre, Barcelona, Spain (E.P.) University of Alberta and Mazankowski Alberta Heart Institute, Edmonton, Alberta, Canada (M.G.) Department of Research, Foundation for Pediatric Cardiology, Institute of Cardiology and Faculty of Health Sciences (Departamento de Investigaciones, Fundación Cardioinfantil-Instituto de Cardiología and Facultad de Ciencias de la Salud), Universidad Autónoma de Bucaramanga, Colombia (J.C.V.) University of Western Ontario, London, Ontario, Canada (M.M.) Department of Clinical Research, Narayana Hrudayalaya Limited, Bangalore, India (A.S.) University of Cape Town and Groote Schuur Hospital, Cape Town, South Africa (B.M.B.) Department of Anaesthesia and Intensive Care, Bispebjerg and Frederiksberg Hospital, University of Copenhagen, Copenhagen, Denmark (C.S.M.) Department of Anesthesiology and Perioperative Medicine, Kingston Health Sciences Centre and Queen's University, Kingston, Canada (J.L.P., I.G.) St. John's Medical College and Research Institute, Bangalore, Karnataka, India (D.X.) Department of Anaesthesia and Intensive Care, The Chinese University of Hong Kong, Hong Kong (M.T.V.C.) University of North Carolina School of Medicine, Chapel Hills, North Carolina (P.A.K.) NHS Grampian and the University of Aberdeen, Aberdeen, United Kingdom (P.F.) Knowledge and Evidence Unite (Unidad de Conocimiento y Evidencia), Universidad Peruana Cayetano Heredia, Lima, Peru (G.M.) Department of Anaesthesia, Intensive Care, and Pain Medicine, Medical University of Vienna, Vienna, Austria (E.F.) Shifa International Hospitals, Islamabad, Pakistan (M.A.) University of the Andes and Santa Maria Clinic (Universidad de Los Andes and Clinica Santa María), Santiago, Chile (D.T.) Department of Anesthesiology, University of Malaya, Kuala Lumpur, Malaysia (C.Y.W.) Biomedical Research Institute (IIB - Sant Pau), Barcelona, Spain (P.P.) Hospital Israelita Albert Einstein, São Paulo, Brazil (O.B.) Department of Surgery, University of Manitoba, Winnipeg, Manitoba, Canada (S.S.) Department of Anesthesia and Intensive Care, IRCCS San Raffaele Scientific Institute and Vita-Salute University, Milan, Italy (G.L.)
Anesthesiology, 2020 04;132(4):692-701.
PMID: 32022771 DOI: 10.1097/ALN.0000000000003158

Abstract

BACKGROUND: The authors previously reported that perioperative aspirin and/or clonidine does not prevent a composite of death or myocardial infarction 30 days after noncardiac surgery. Moreover, aspirin increased the risk of major bleeding and clonidine caused hypotension and bradycardia. Whether these complications produce harm at 1 yr remains unknown.

METHODS: The authors randomized 10,010 patients with or at risk of atherosclerosis and scheduled for noncardiac surgery in a 1:1:1:1 ratio to clonidine/aspirin, clonidine/aspirin placebo, clonidine placebo/aspirin, or clonidine placebo/aspirin placebo. Patients started taking aspirin or placebo just before surgery; those not previously taking aspirin continued daily for 30 days, and those taking aspirin previously continued for 7 days. Patients were also randomly assigned to receive clonidine or placebo just before surgery, with the study drug continued for 72 h.

RESULTS: Neither aspirin nor clonidine had a significant effect on the primary 1-yr outcome, a composite of death or nonfatal myocardial infarction, with a 1-yr hazard ratio for aspirin of 1.00 (95% CI, 0.89 to 1.12; P = 0.948; 586 patients [11.8%] vs. 589 patients [11.8%]) and a hazard ratio for clonidine of 1.07 (95% CI, 0.96 to 1.20; P = 0.218; 608 patients [12.1%] vs. 567 patients [11.3%]), with effect on death or nonfatal infarction. Reduction in death and nonfatal myocardial infarction from aspirin in patients who previously had percutaneous coronary intervention at 30 days persisted at 1 yr. Specifically, the hazard ratio was 0.58 (95% CI, 0.35 to 0.95) in those with previous percutaneous coronary intervention and 1.03 (95% CI, 0.91to 1.16) in those without (interaction P = 0.033). There was no significant effect of either drug on death, cardiovascular complications, cancer, or chronic incisional pain at 1 yr (all P > 0.1).

CONCLUSIONS: Neither perioperative aspirin nor clonidine have significant long-term effects after noncardiac surgery. Perioperative aspirin in patients with previous percutaneous coronary intervention showed persistent benefit at 1 yr, a plausible sub-group effect.

* Title and MeSH Headings from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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