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

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 (I2 = 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.