title: Stopping antiplatelet medication before coronary artery bypass graft surgery: is there an optimal timing to minimize bleeding?
abstract: OBJECTIVE
  As the indication for antiplatelet medication expands, patients may be exposed to an increased risk of excessive blood loss when cardiac surgery is required. The optimal timing to stop acetylsalicylic acid (ASA) or ASA combined with clopidogrel (ASA+Clo) before surgery is the subject of controversy.
  
  
  METHODS
  A total of 1065 patients were selected from a prospective randomized study on the effect of a fibrin sealant application in coronary artery bypass graft surgery [Fibrin sealant Induced Blood Exposure Reduction study;
  
  
  BACKGROUND
  NTR1386 (http://www.trialregister.nl)], and divided into three groups according to the use of antiplatelet medication within 10 days prior to surgery: (i) ASA only (n = 662), (ii) ASA+Clo (n = 290) or (iii) no antiplatelet medication (n = 113). To investigate if an optimal stop day could be established, we fitted a series of multiple linear regression models, one for each preoperative day (running from Day -10 up to -1). The specific day corresponding to the best fitting model (highest adjusted R(2), with blood loss in the first 48 h postoperatively as the dependent variable) was considered as the best estimate for the optimal stop day. Bootstrap analysis (1000 times) was performed to calculate the corresponding confidence interval. Furthermore, major adverse cardiovascular and cerebral events (MACCE) were evaluated.
  
  
  RESULTS
  We could not estimate an optimal stop day for patients using ASA or ASA+Clo prior to their operation. Last use of ASA on Day -2 or earlier significantly decreased the percentage of patients receiving platelet transfusions compared with continuation until surgery (7 vs 13% for Day -1, P = 0.007). In patients using ASA+Clo, this percentage was reduced from 41 to 10 (P < 0.001). There was no association between stop day and the occurrence of MACCE.
  
  
  CONCLUSIONS
  There is no clinically relevant effect on blood loss indicating an optimal stop day for ASA alone or in combination with Clo. Last use on Day -2 resulted in the reduction of percentage of patients receiving platelet transfusions, especially in the ASA+Clo group.
authors.affiliation: Department of Cardiothoracic Surgery, Leiden University Medical Center (LUMC), Leiden, Netherlands.
authors.forename: Chantal L I
authors.initials: CL
authors.lastname: Gielen
authors.affiliation: Department of Cardiothoracic Surgery, Leiden University Medical Center (LUMC), Leiden, Netherlands.
authors.forename: Eline F
authors.initials: EF
authors.lastname: Bruggemans
authors.affiliation: Department of Medical Statistics, Leiden University Medical Center (LUMC), Leiden, Netherlands.
authors.forename: Theo
authors.initials: T
authors.lastname: Stijnen
authors.affiliation: Department of Thrombosis and Hemostasis, Leiden University Medical Center (LUMC), Leiden, Netherlands.
authors.forename: Jeroen
authors.initials: J
authors.lastname: Eikenboom
authors.affiliation: Department of Cardiothoracic Surgery, Leiden University Medical Center (LUMC), Leiden, Netherlands.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Tavilla
authors.affiliation: Sanquin Blood Bank, Leiden, Netherlands Department of Immunohematology and Blood Transfusion, Leiden University Medical Center (LUMC), Leiden, Netherlands.
authors.forename: Anneke
authors.initials: A
authors.lastname: Brand
authors.affiliation: Department of Cardiothoracic Surgery, Leiden University Medical Center (LUMC), Leiden, Netherlands r.j.m.klautz@lumc.nl.
authors.forename: Robert J M
authors.initials: RJ
authors.lastname: Klautz
mesh_terms: D000368:Aged; D001241:Aspirin / Q000008:administration & dosage* / Q000009:adverse effects; D016063:Blood Loss, Surgical / Q000517:prevention & control*; D000077144:Clopidogrel; D001026:Coronary Artery Bypass / Q000009:adverse effects / Q000379:methods*; D003324:Coronary Artery Disease / Q000175:diagnosis / Q000401:mortality / Q000601:surgery; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects; D017713:Platelet Transfusion / Q000706:statistics & numerical data; D019106:Postoperative Hemorrhage / Q000517:prevention & control; D011446:Prospective Studies; D018570:Risk Assessment; D012680:Sensitivity and Specificity; D013988:Ticlopidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D013997:Time Factors; D016896:Treatment Outcome; D028761:Withholding Treatment
chemical_list: D010975:Platelet Aggregation Inhibitors; D000077144:Clopidogrel; D013988:Ticlopidine; D001241:Aspirin
keywords: Blood loss; Coronary artery bypass; Platelet aggregation inhibitors; Surgical