Antiplatelet therapy after coronary bypass grafting: which regimen and for whom?

This editorial refers to ‘Differential effects of dual antiplatelet therapy in patients presented with acute coronary syndrome vs. stable ischaemic heart disease after coronary artery bypass grafting', by K.H. Choi et al., doi:10.1093/ehjcvp/pvaa080. Dual antiplatelet therapy (DAPT) with aspirin and a P2Y12-receptor inhibitor is the recommended antithrombotic treatment for patients undergoing coronary bypass grafting (CABG) in the context of an acute coronary syndrome (ACS) (1, 2). Nonetheless, substantial variability in clinical practice has been shown, with less than 50% of cardiac surgeons reporting to routinely use DAPT following CABG in ACS (3). Less certain is the indication for DAPT in patients undergoing CABG in the context of stable ischaemic heart disease (SIHD), owing to the incomplete definition of the benefit-to-risk ratio of DAPT vs. SAPT as regards graft patency (and associated risk of adverse events) vs. increased risk of bleeding (4). Accordingly, inconsistency between recommendations is apparent, with the European Society of Cardiology guidelines giving no indication for DAPT and the American College of Cardiology/American Heart Association guidelines reporting that DAPT may actually be considered (1, 2). The work of Choi et al. (5) is therefore welcome as it sheds some further light on this controversial issue. The 5-year incidence of cardiovascular death or myocardial infarction (MI) in 5782 patients undergoing CABG, either in the context of an ACS (55.3%) or SIHD (44.7%), and receiving DAPT with aspirin and (generally) clopidogrel (56.6%) or SAPT with aspirin (43.4%), was retrospectively analysed (5). During follow-up, patency of 6274 grafts in 2918 patients (50.5%) was assessed by either computed tomography or invasive coronary angiography (5). Overall, DAPT, which was given for a mean of 19 months, was associated with a 31% significantly lower risk of cardiovascular death or MI as compared to SAPT, at the price of a 46% significant increase in the risk of major bleeding (5). A statistically significant interaction was observed between the use of DAPT and clinical presentation: in ACS patients, DAPT was associated with a 48% significantly lower risk of cardiovascular death or MI, with a non-significant increase in major bleeding, whereas in SIHD patients the rate of cardiovascular death or MI was comparable between DAPT and SAPT, with a non-significant increase in major bleeding with DAPT (5). In ACS patients, secondary outcomes, including cardiovascular death (-75%), all-cause death (-51%), and major adverse cardiovascular events (a composite of cardiovascular death, MI, and stroke) (-31%), were also significantly lower with DAPT as compared to SAPT (5). In SIHD patients, a significant interaction between antiplatelet regimen (DAPT vs. SAPT) and history of PCI was observed, with a significantly lower risk of cardiovascular death or MI with DAPT when PCI had been previously performed (5). As regards graft patency, no difference was observed between DAPT and SAPT, although in ACS patients the incidence of graft failure during follow-up was numerically lower with DAPT (5). When aiming at taking home some practical messages from the work of Choi et al. (5), its several limitations, including the single-centre design, lack of randomization, nearly no use of the newer and more potent P2Y12-receptor inhibitors ticagrelor and prasugrel, lack of systematic evaluation of graft patency, and absence of data regarding adherence to treatment and complexity of coronary artery disease, need to be acknowledged. Nonetheless, the data provided are of value as they support the long and well established concept that DAPT is highly beneficial in ACS where is the clinical presentation dominating over the therapeutic strategy, i.e., CABG vs. PCI vs. medical management, in driving the choice of the antiplatelet regimen. In the context of the intense platelet activation of ACS, the favourable effect of DAPT in preventing thrombus formation is obtained at either an inserted coronary artery bypass and/or an implanted stent and/or an atherosclerotic plaque in a native vessel. In contrast, in SIHD patients at lower risk of spontaneous thrombotic events no benefit appears to be expected with DAPT vs. SAPT following CABG, in terms of neither graft patency nor adverse ischaemic events, in the absence however of a significant increase in the risk of bleeding (5). The reported benefit of DAPT in patients with previous PCI (5) might again be related to the effective prevention of stent thrombosis, which can occur even years after implantation (6), especially with first-generation drug-eluting stents, which were certainly used in the early 2000s when patient inclusion started and these drug-eluting stents were the only available. In conclusion, the results of Choi et al. (5) further support the current recommendations to routinely administer DAPT with aspirin and clopidogrel following CABG in ACS patients. In contrast, SAPT with aspirin should generally be regarded as the default antiplatelet therapy for patients undergoing CABG in the context of SIHD. More evidence is needed to better define the optimal antiplatelet therapy in specific subgroups of CABG patients, such as, those undergoing on-pump and/or receiving saphenous vein grafts and/or undergoing endarterectomy, given their differences in the risk of graft failure. Also, further prospective, randomised studies investigating different combinations and/or monotherapy with the newer and more potent P2Y12-receptor inhibitors are warranted. One of them, the POPular CABG trial (7) evaluating the effect of ticagrelor on saphenous vein CABG, is underway. Conflict of interest: A.R. reports lecture fees from and/or consulting for Astra Zeneca, Bayer Healthcare and Daichi Sankyo. S.V. reports no conflicts of interest.