Hrvoje Gasparovic (Department of Cardiac Surgery, University Hospital Center Zagreb, Zagreb, Croatia) and others write in The American Journal of Cardiology that the combination of aspirin and clopidogrel (or dual antiplatelet therapy) does not significantly reduce the risk of adverse events in aspirin-resistant patients who have undergone coronary artery bypass grafting (CABG) compared with aspirin monotherapy.
The authors write that some studies have indicated that dual antiplatelet therapy may improve venous graft patency, compared with aspirin monotherapy, in CABG patients but say that the benefit has not been “reliably reproduced in a wider clinical trial.” They add that dual platelet inhibition “may be of particular importance in patients exhibiting single antiplatelet drugs resistance.” Therefore, the aim of their study was to randomise aspirin-resistant CABG patients to either aspirin monotherapy or a combination of clopidogrel and aspirin. The primary outcome was the incidence of major adverse cardiac events and cerebrovascular events (MACCE) at six months while secondary endpoints included bleeding events and individual MACCE components.
Of the 224 aspirin-resistant patients (identified via aggregometry-based assessment of their on-aspirin platelet reactivity), 110 were randomised to receive aspirin monotherapy and 114 were randomised to receive dual antiplatelet therapy (aspirin plus clopidogrel). At the six-month follow-up, there were no significant differences in the rate of the primary endpoint between groups—10% for the control group vs. 6% for the dual antiplatelet group (two-tailed p=0.33 and one-tailed p=0.20). Also, there were no significant differences in the individual components (all-cause mortality, non-fatal myocardial infarction, cerebrovascular accident, and cardiovascular hospitalisation) of the MACCE endpoints between the groups. There were no significant differences between the dual antiplatelet group and the aspirin monotherapy group in the rate of bleeding.
However, subgroup analyses revealed that there was a significant difference in the MACCE rate between the dual antiplatelet therapy group and aspirin monotherapy groups in patients who were ≤65 years (0% vs. 10%, respectively; p=0.02) and obese patients (0% vs. 18%, respectively; p<0.01)
Gasparovic et al comment that although their study did not find dual antiplatelet therapy conferred a significant benefit in overall patient cohort, the finding that it did appear to be beneficial in obese or younger aspirin-resistant patients warranted further study.
Gasparovic told Cardiovascular News: “Combining antiplatelet agents with different mechanisms of platelet inhibition harbours potential to reduce both the incidence and impact of high on-therapy platelet reactivity. In our study we used clopidogrel to augment platelet inhibition among CABG patients found to be aspirin-resistant. The complex activation sequence of clopidogrel is responsible for its large inter-individual variability in platelet inhibition. Newer generation P2Y12 inhibitors require fewer activation steps (prasugrel) or none at all (ticagrelor), which makes them more resistant to the idiosyncrasies of intrinsic biotransformation. The more consistent platelet inhibition induced by newer P2Y12 inhibitors could, hypothetically, have a greater impact on reducing the incidence of adverse events among patients found to be aspirin-resistant. The benefits of enhanced antiplatelet therapy must, however, be balanced against the increased risk of bleeding. Randomised trials should define the role of specific drug combinations before wider dissemination can be recommended without reservations.”