We read the recently published study by Bomb et al. In their report, the investigators reviewed the available evidence to rule out the efficacy and safety of dual antiplatelet therapy (DAPT) after coronary artery bypass grafting (CABG) in the setting of the acute coronary syndrome. Based on the extensive review of the literature, the investigators concluded that the appropriate antiplatelet regimen after CABG remains elusive and there is no clear consensus regarding the use of DAPT after CABG.

In our opinion, when assessing the impact of the antiplatelet therapy (APT) administration management on both bleeding and adverse ischemic events, objective quantification of “on-treatment” platelet reactivity should inextricably be included into considerations.

Platelet inhibitory response to APT varies widely in subjects. Moreover, platelet reactivity does not vary only between subjects but also the individual patients may express widely different platelet reactivity across different time points that are often influenced by different clinical conditions.

Our working group extensively investigates the phenomenon of individual variability in platelet reactivity and in variability in response to APT. In our previous study, we evaluated aspirin resistance (AR) perioperatively in patients who underwent CABG. Preoperatively, we detected 31.3% of patients with AR. In postoperative phase, higher proportion of patients (46.5%) had AR. This significant increase in prevalence of AR in early postoperative period confirms partially the hypothesis that on-pump surgery can induce inflammation, causing platelet hyperactivity and enhancing the rate of patients with AR, which in turn may be responsible for adverse ischemic events occurrence.

Based on these findings, we conducted randomized controlled trial aiming to test the hypothesis that the addition of clopidogrel to patients with documented postoperative AR will reduce the incidence of major adverse cardiac and cerebrovascular events (MACCEs). To the best of our knowledge, that was the first and, to date, the only 1 published study that specifically addressed the issue of DAPT in patients with CABG with documented AR. Put briefly, patients with documented AR were randomly assigned to receive DAPT (clopidogrel 75 mg + aspirin 300 mg) or aspirin 300 mg monotherapy. The primary end point (MACCEs) occurred in 6% of patients assigned to DAPT and 10% of patients randomized to aspirin monotherapy. DAPT led to lower rates of adverse events in patients with a body mass index >30 kg/m ² (0% vs 18%, p <0.01) and those <65 years (0% vs 10%, p = 0.02). Higher incidence of bleeding events in the DAPT group (25% vs 19%) did not reach statistical significance.

We cannot reliably exclude the possibility that the study may have actually been underpowered but certainly provides an impetus for the conduct of a larger scale study of a similar design. Moreover, with the aim to evaluate the clinical relevance of AR, we performed exploratory analysis of our randomized controlled trial database and compared patients with AR and those with adequate response to aspirin. Subgroup analysis revealed that aspirin-resistant patients with body mass index >30 kg/m ² tend to have a higher occurrence of MACCEs relative to aspirin-sensitive patients (18% vs 5%, p = 0.05). Our findings suggest that further sufficiently powered studies are needed to define optimal APT management.

Evaluation of APT effect on both bleeding and adverse ischemic events should be based on platelet function assessment with subsequent distinction of patients with high residual platelet activity, thus proclivity to ischemic events, or enhanced platelet inhibition, thus proclivity to excessive bleeding.

For patients who underwent CABG, individually tailored APT administration management, based on platelet function testing, can help reduce both bleeding and ischemic events.

Such an approach requires further studies to provide precise and comprehensive view on the relation between APT administration management and both, bleeding and ischemic events, through achieved platelet inhibition quantified by platelet function tests.

One of the major drawbacks of our randomized controlled trial was that platelet inhibitory response to clopidogrel was not assessed in the DAPT group. The negligible rate of clopidogrel resistance certainly requires the assessment of platelet ADP receptor activity while on clopidogrel therapy. That a patient is treated by the DAPT does not necessarily mean that patient has achieved adequate platelet inhibition. According to our findings, there is wide interindividual variability in inherent ADP receptor activity. In contrast, the effect of clopidogrel or any other ADP receptor blocker depends on (1) baseline-inherent ADP receptor activity and (2) platelet inhibitory response to the ADP receptor blocker. Considering wide variability in inherent platelet ADP receptor activity and wide variability in platelet inhibitory response to ADP receptor blockers, we should not be surprised by negative studies evaluating the role of DAPT.

It seems that the “one-size-fits-all” concept of APT administration is outdated, and further development of personalized APT management based on platelet function testing is desirable.