Should dual antiplatelet therapy be used in patients following coronary artery bypass surgery? A meta-analysis of randomized controlled trials

Subodh Verma, Shaun G. Goodman, Shamir R. Mehta, David A. Latter, Marc Ruel, Milan Gupta, Bobby Yanagawa, Mohammed Al-Omran, Nandini Gupta, Hwee Teoh, Jan O. Friedrich

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). 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. 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). 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.