Use of platelet function testing to guide the timing of coronary artery bypass surgery

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Excerpt

Coronary artery bypass grafting (CABG) is the most appropriate revascularization strategy for selected patients after acute myocardial infarction (MI). Optimal timing for surgery remains an area of debate. One factor influencing the decision regarding optimal timing is the frequent use of P2Y12 inhibitors in these patients. Food and Drug Administration-approved labeling recommends discontinuation of P2Y12 inhibitors 5–7 days before CABG with a specific recommendation for discontinuation of prasugrel 7 days before surgery 1. This guideline is based on clinical experience, results of pharmacodynamic testing, and the association between bleeding and mortality in patients undergoing CABG. Orvin and colleagues propose serial testing of platelet function as a method to individualize decisions for selected patients. The authors hypothesize that this individualized approach should facilitate less delay before surgery without an associated increase in the prevalence of bleeding.
One challenge associated with the use of platelet function testing to guide clinical decisions as proposed by Orvin and colleagues is that, although the assessment of platelet function has been associated with a greater risk for subsequent thrombotic events (such as MI), it has not been demonstrated to effectively predict the risk for bleeding 2. Further, despite the consistent association between increased platelet reactivity and a greater risk for subsequent MI, individualized antiplatelet therapy based on the results of platelet function testing has not been shown to reduce the risk for subsequent cardiovascular events 3,4. On the basis of these results, platelet function testing cannot be recommended to individualize antiplatelet therapy 5. In contrast to those recommendations, Orvin and colleagues are using platelet function testing in a different manner, to identify the recovery of platelet function. Nevertheless, previous challenges regarding the use of platelet function testing to individualize therapy underscores comments by the authors that call for larger prospective clinical trials to demonstrate the utility of the proposed approach.
Factors other than the risk for bleeding may also impact outcomes when CABG is used as the revascularization strategy after MI. Retrospective analyses suggest that delaying CABG after MI may improve outcomes 6. Retrospective analyses are confounded by differences in patient characteristics. Patients who are most critically ill are likely to undergo surgery early after MI. Thus, the greater risk may reflect primarily the acuity of their illness rather than a true benefit associated with a delay in surgery. Concern over the risk for thrombotic events (MI) is often a factor favoring early surgery. Retrospective studies reported a low risk (mortality of 0.4%) associated with delay before CABG 7,8. Once again, the retrospective nature of these studies limits extrapolation to guide practice. Nevertheless, these results support an approach in which CABG is delayed unless patient acuity dictates earlier surgery. A prospective trial designed to test an individualized approach guided by recovery of platelet function will provide insight regarding the balance between risks associated with delay and potential benefits associated with a reduction in the prevalence of bleeding.
Perhaps paradoxically in light of the risk for bleeding, antiplatelet therapy may be beneficial in patients undergoing CABG. Previous studies have demonstrated that CABG leads to the activation of platelets and the release of young platelets that are known to be more reactive and hence prothrombotic 9. Thus, antiplatelet agents may prevent thrombotic complications during and shortly after CABG. Evidence in support of this hypothesis was provided by the Study of Platelet Inhibition and Patient Outcomes (PLATO). Among patients who had undergone CABG, those randomized to ticagrelor compared with clopidogrel had a lower mortality (ticaglelor 4.7%, clopidogrel 9.7%, P<0.01) 10.

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