title: Should dual antiplatelet therapy be used in patients following coronary artery bypass surgery? A meta-analysis of randomized controlled trials.
abstract: BACKGROUND
  We assessed the effectiveness of dual antiplatelet therapy (DAPT) post elective or urgent (i.e., post acute coronary syndrome [ACS]) coronary artery bypass graft surgery (CABG).
  
  
  METHODS
  We systematically searched MEDLINE, EMBASE, and the Cochrane Registry from inception to August 2015. Randomized controlled trials (RCTs) in adults undergoing CABG comparing either dual vs. single antiplatelet therapy or higher- vs. lower-intensity DAPT were identified.
  
  
  RESULTS
  Nine RCTs (n = 4,887) with up to 1y follow-up were included. Five RCTs enrolled patients post-elective CABG (n = 986). Two multi-centre RCTs enrolled ACS patients who subsequently underwent CABG (n = 2,155). These 7 RCTs compared clopidogrel plus aspirin to aspirin alone. Two other multi-centre RCTs reported on ACS patients who subsequently underwent CABG comparing higher intensity DAPT with either ticagrelor (n = 1,261) or prasugrel (n = 485) plus aspirin to clopidogrel plus aspirin. Post-operative anti-platelet therapy was started when chest tube bleeding was no longer significant, typically within 24-48 h. There were no differences in all-cause mortality in clopidogrel plus aspirin vs. aspirin RCTs; conversely, all-cause mortality was significantly lower in ticagrelor and prasugrel vs. clopidogrel RCTs (risk ratio[RR] 0.49, 95% confidence interval[CI] 0.33-0.71, p = 0.0002; 2 RCTs, n = 1695; I(2)  = 0%; interaction p < 0.01 compared to clopidogrel plus aspirin vs aspirin RCTs). There were no differences in myocardial infarctions, strokes, or composite outcomes. Overall, major bleeding was not significantly increased (RR 1.31, 95% CI 0.81-2.10, p = 0.27; 7 RCTs, n = 4500). There was heterogeneity (I(2)   = 42%) due almost entirely to higher bleeding reported for the prasugrel RCT which included mainly CABG-related major bleeding (RR 3.15, 95% CI 1.45-6.87, p = 0.004; 1 RCT, n = 437).
  
  
  CONCLUSIONS
  Most RCT data for DAPT post CABG is derived from subgroups of ACS patients in DAPT RCTs requiring CABG who resume DAPT post-operatively. Limited RCT data with heterogeneous trial designs suggest that higher intensity (prasugrel or ticagrelor) but not lower intensity (clopidogrel) DAPT is associated with an approximate 50% lower mortality in ACS patients who underwent CABG based on post-randomization subsets from single RCTs. Large prospective RCTs evaluating the use of DAPT post-CABG are warranted to provide more definitive guidance for clinicians.
authors.affiliation: Division of Cardiac Surgery, Keenan Research Centre for Biomedical Science and Li Ka Shing Knowledge Institute of St. Michael's Hospital, Toronto, ON, M5B 1W8, Canada. vermasu@smh.ca.|Department of Surgery, St. Michael's Hospital, Toronto, ON, M5B 1W8, Canada. vermasu@smh.ca.|Department of Surgery, University of Toronto, Toronto, ON, M5S 2J7, Canada. vermasu@smh.ca.|King Saud University, Riyadh, 12372, Saudi Arabia. vermasu@smh.ca.
authors.forename: Subodh
authors.initials: S
authors.lastname: Verma
authors.affiliation: Division of Cardiology, Li Ka Shing Knowledge Institute of St. Michael's Hospital, Toronto, ON, M5B 1W8, Canada.|Department of Medicine, St. Michael's Hospital, Toronto, ON, M5B 1W8, Canada.|Department of Medicine, University of Toronto, Toronto, ON, M5S 2J7, Canada.
authors.forename: Shaun G
authors.initials: SG
authors.lastname: Goodman
authors.affiliation: Department of Medicine, McMaster University, Hamilton, ON L8L 2X2, Canada.|Population Health Research Institute, Hamilton Health Sciences, Hamilton, ON, L8L 2X2, Canada.
authors.forename: Shamir R
authors.initials: SR
authors.lastname: Mehta
authors.affiliation: Division of Cardiac Surgery, Keenan Research Centre for Biomedical Science and Li Ka Shing Knowledge Institute of St. Michael's Hospital, Toronto, ON, M5B 1W8, Canada.|Department of Surgery, St. Michael's Hospital, Toronto, ON, M5B 1W8, Canada.|Department of Surgery, University of Toronto, Toronto, ON, M5S 2J7, Canada.
authors.forename: David A
authors.initials: DA
authors.lastname: Latter
authors.affiliation: University of Ottawa Heart Institute, Ottawa, ON, K1Y 4W7, Canada.
authors.forename: Marc
authors.initials: M
authors.lastname: Ruel
authors.affiliation: Department of Medicine, University of Toronto, Toronto, ON, M5S 2J7, Canada.|Department of Medicine, McMaster University, Hamilton, ON L8L 2X2, Canada.|Canadian Cardiovascular Research Network, Brampton, ON, L6Z 4N5, Canada.
authors.forename: Milan
authors.initials: M
authors.lastname: Gupta
authors.affiliation: Division of Cardiac Surgery, Keenan Research Centre for Biomedical Science and Li Ka Shing Knowledge Institute of St. Michael's Hospital, Toronto, ON, M5B 1W8, Canada.|Department of Surgery, St. Michael's Hospital, Toronto, ON, M5B 1W8, Canada.|Department of Surgery, University of Toronto, Toronto, ON, M5S 2J7, Canada.
authors.forename: Bobby
authors.initials: B
authors.lastname: Yanagawa
authors.affiliation: Division of Vascular Surgery, Keenan Research Centre for Biomedical Science and Li Ka Shing Knowledge Institute of St. Michael's Hospital, Toronto, ON, M5B 1W8, Canada.|Department of Surgery, St. Michael's Hospital, Toronto, ON, M5B 1W8, Canada.|Department of Surgery, University of Toronto, Toronto, ON, M5S 2J7, Canada.|King Saud University, Riyadh, 12372, Saudi Arabia.
authors.forename: Mohammed
authors.initials: M
authors.lastname: Al-Omran
authors.affiliation: The Ottawa Hospital, Ottawa, ON, K1H 8L6, Canada.
authors.forename: Nandini
authors.initials: N
authors.lastname: Gupta
authors.affiliation: Division of Cardiac Surgery, Keenan Research Centre for Biomedical Science and Li Ka Shing Knowledge Institute of St. Michael's Hospital, Toronto, ON, M5B 1W8, Canada.|Division of Endocrinology & Metabolism, Keenan Research Centre for Biomedical Science and Li Ka Shing Knowledge Institute of St. Michael's Hospital, Toronto, ON, M5B 1W8, Canada.|Department of Surgery, St. Michael's Hospital, Toronto, ON, M5B 1W8, Canada.|Department of Medicine, St. Michael's Hospital, Toronto, ON, M5B 1W8, Canada.
authors.forename: Hwee
authors.initials: H
authors.lastname: Teoh
authors.affiliation: Department of Medicine, St. Michael's Hospital, Toronto, ON, M5B 1W8, Canada. FriedrichJ@smh.ca.|Department of Critical Care, St. Michael's Hospital, Toronto, ON, M5B 1W8, Canada. FriedrichJ@smh.ca.|Department of Medicine, University of Toronto, Toronto, ON, M5S 2J7, Canada. FriedrichJ@smh.ca.|Interdepartmental Division of Critical Care, University of Toronto, Toronto, ON, M5S 2J7, Canada. FriedrichJ@smh.ca.
authors.forename: Jan O
authors.initials: JO
authors.lastname: Friedrich
mesh_terms: D054058:Acute Coronary Syndrome / Q000628:therapy*; D001026:Coronary Artery Bypass; D004359:Drug Therapy, Combination; D006801:Humans; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use*; D011182:Postoperative Care / Q000379:methods*; D016032:Randomized Controlled Trials as Topic
chemical_list: D010975:Platelet Aggregation Inhibitors