Fig. 4
Forest plot for major bleeding. Individual and pooled risk ratios (RR) with 95 % confidence intervals (CI) for randomized controlled trials (RCTs) comparing dual anti-platelet therapy with clopidogrel and ASA to single anti-platelet therapy with ASA alone either after elective coronary artery bypass graft surgery (CABG) [16, 21–23] or in patients with acute coronary syndrome (ACS) who subsequently underwent CABG [19], and RCTs comparing higher to lower intensity dual anti-platelet therapy with either ticagrelor [17] or prasugrel [11] and ASA vs clopidogrel and ASA in patients with ACS who subsequently underwent CABG. The pooled RRs with 95 % CI were calculated using random-effects models both overall and for each subgroup. Weight refers to the contribution of each study to the overall pooled estimate of treatment effect. Each square and horizontal line denotes the point estimate and 95 % CI for each trial’s RR. The diamonds signify the pooled RR for all trials and each subgroup; the diamond’s centre denotes the point estimate and width denotes the 95 % CI. The clopidogrel plus ASA vs ASA trials used either CURE trial [19, 21, 22], Bleeding Academic Research Consortium (BARC) Type 3–5 [23] (all BARC Type 3 for this trial [i.e., no CABG-related {Type 4} or fatal {Type 5} bleeding]), or similar [16] criteria for major bleeding and reported events that were either non-CABG related [16, 21–23] or more than 7 days post CABG [19]. The higher-intensity vs lower-intensity dual anti-platelet PLATO [17] and TRITON-TIMI 38 trials reported bleeding using TIMI criteria and included CABG related bleeding which made up the vast majority of the bleeding events (non-CABG related bleeding data was not available for the ACS CABG patients in these RCTs). If TIMI criteria are used for the CURE trial [19], the pooled results are essentially unchanged (RR 1.25, 95 % CI 0.71–2.19, p = 0.43; I2 = 48 %). Excluding TRITON TIMI 38 [11] from the pooled results eliminates the heterogeneity (I2 = 0 %)