title: Impact of preoperative use of P2Y12 receptor inhibitors on clinical outcomes in cardiac and non-cardiac surgery: A systematic review and meta-analysis.
abstract: OBJECTIVE
  To review systematically the evidence and perform a meta-analysis of benefits and risks associated with use of P2Y12receptor inhibitors in coronary artery bypass graft-, non-cardiac- and device surgery. Data selection and analysis: We performed a meta-analysis of published studies. Patients with preoperative use of clopidogrel, ticagrelor or prasugrel (late discontinuation: <5 days before surgery or no discontinuation) were compared with patients without preoperative use of the respective drug (early discontinuation: ⩾5 days before surgery or no users of P2Y12receptor inhibitors). Outcomes evaluated were re-operation for major bleeding, death, myocardial infarction, combined major adverse cardiac events (MACEs) and major haematoma. Using a random effect model, relative risks (RRs) and 95% confidence intervals (CI) were calculated for each outcome.
  
  
  RESULTS
  Fifty-four studies met the selection criteria and included 50,048 patients. Preoperative use of clopidogrel on top of aspirin in patients undergoing coronary artery bypass graft was associated with a 2.5-fold increased risk of re-operation for bleeding (95% CI: 1.92-3.25; p<0.001) and a 1.47-fold increased risk of death (95% CI: 1.25-1.72; p<0.001), but did not diminish the risk for myocardial infarction (RR: 0.96; 95% CI: 0.75-1.25; p=0.18) or MACE (RR: 1.16; 95% CI: 0.90--1.50; p=0.30). In patients undergoing non-cardiac surgery, preoperative use of clopidogrel increased the RR of re-operation for major bleeding by 2.05-fold (95% CI: 1.13-3.73; p=0.002) but did not reduce the RR for MACE or death. Clopidogrel use during cardiac device implantation raised the RR for procedure-related haematoma by 3.0-fold (95% CI: 1.30--6.94; p=0.001). Whereas preoperative ticagrelor use did not increase the risk for mortality (RR: 1.03; 95% CI: 0.49-2.14), preoperative prasugrel use tended to increase the risk for death (RR: 5.06; 95% CI: 0.54-47.65).
  
  
  CONCLUSIONS
  Preoperative exposure to clopidogrel on top of aspirin did not reduce the risk of MACE but was associated with increased risk of bleeding and mortality.
authors.affiliation: 1 Department of Cardiology, Medical University of Vienna, Austria.
authors.forename: Jolanta M
authors.initials: JM
authors.lastname: Siller-Matula
authors.affiliation: 1 Department of Cardiology, Medical University of Vienna, Austria.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Petre
authors.affiliation: 1 Department of Cardiology, Medical University of Vienna, Austria.
authors.forename: Georg
authors.initials: G
authors.lastname: Delle-Karth
authors.affiliation: 2 3rd Medical Department of Cardiology and Emergency Medicine, Wilhelminen Hospital, Vienna, Austria.
authors.forename: Kurt
authors.initials: K
authors.lastname: Huber
authors.affiliation: 3 Division of Haematology and Haemostaseology, Department of Medicine I, Medical University of Vienna, Austria.
authors.forename: Cihan
authors.initials: C
authors.lastname: Ay
authors.affiliation: 4 Faculty of Pharmacy, University of Montreal; Research Center, Montreal Heart Institute, Canada.
authors.forename: Marie
authors.initials: M
authors.lastname: Lordkipanidzé
authors.affiliation: 5 Institute of Cardiology, 'G d'Annunzio' University - Chieti-Pescara, Chieti, Italy.
authors.forename: Raffaele
authors.initials: R
authors.lastname: De Caterina
authors.affiliation: 6 Department of Cardiothoracic Surgery, University Hospital of Liege, Belgium.
authors.forename: Philippe
authors.initials: P
authors.lastname: Kolh
authors.affiliation: 7 Department of Anaesthesiology and Intensive Care Medicine, Medical University of Graz, Austria.
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Mahla
authors.affiliation: 8 Division of Cardiovascular Diseases, Department of Internal Medicine, Mayo Clinic, College of Medicine Rochester, USA.
authors.forename: Bernard J
authors.initials: BJ
authors.lastname: Gersh
mesh_terms: D006348:Cardiac Surgical Procedures; D003324:Coronary Artery Disease / Q000150:complications / Q000188:drug therapy / Q000601:surgery; D006801:Humans; D011300:Preoperative Care / Q000379:methods*; D011379:Prognosis; D058921:Purinergic P2Y Receptor Antagonists / Q000627:therapeutic use*; D013514:Surgical Procedures, Operative
chemical_list: D058921:Purinergic P2Y Receptor Antagonists
keywords: CABG; Clopidogrel; prasugrel; surgery; ticagrelor