Perspective:

The following are 10 points to remember about this Expert Position Paper:

1. Optimizing outcomes after percutaneous coronary intervention (PCI) requires balancing between the risks of thrombotic and bleeding events in individual patients. High on-treatment platelet reactivity (HPR) has been associated with a significant increase in nonfatal myocardial infarction, definite/probable stent thrombosis, or cardiovascular mortality by four independent meta-analyses.

2. Based on the currently available evidence, the recommended assays for monitoring platelet inhibition during P2Y₁₂ inhibitors are the VerifyNow P2Y₁₂ assay, the Multiplate device with the ADP kit, and the vasodilator-stimulated phosphoprotein (VASP) assay. Although the optimal thresholds to define a higher risk for thrombotic events may depend on the clinical situation and are still under investigation, available evidence suggests 208 PRU with the VerifyNow, 46 U with the Multiplate assay, and 50% with the VASP assay.

3. HPR to ADP is a strong and independent predictor of adverse thrombotic events, especially early stent thrombosis in patients on clopidogrel after PCI. The association is stronger in patients with acute coronary syndrome, while less established in patients with stable angina.

4. In patients managed without revascularization, HPR is not an independent predictor of recurrent ischemic events; therefore, platelet function testing to change antiplatelet strategy is not recommended in this subset.

5. Platelet function testing may be considered if results may change the P2Y₁₂ inhibitor strategy due to: (i) unexpected definite stent thrombosis despite being adherent to clopidogrel; (ii) markedly elevated risk for stent thrombosis (prior stent thrombosis or complex stenting procedure in high-risk patients), and (iii) last remaining vessel or unprotected left main stem PCI involving the bifurcation. The final decision making on the preferred P2Y₁₂ inhibitor should incorporate both the platelet function result and the bleeding risk of the patient.

6. Although evidence is culminating, the link between low on-treatment platelet reactivity (LPR) and bleeding events in PCI patients exposed to P2Y₁₂ inhibitors is not as clearly established as for HPR and stent thrombosis.

7. In selected patients who experience a major bleeding event during P2Y₁₂ inhibitor treatment and remain at increased risk for recurrent bleeding, platelet function testing might be considered to determine the potency of platelet inhibition and to facilitate the optimal P2Y₁₂ inhibitor strategy during/after the bleeding episode.

8. The main reason why platelet function testing has a low level of recommendation in guidelines (Class IIb) and a restrictive indication in current guidelines is the lack of adequately sized, positive, randomized, controlled studies to show an improvement in clinical outcomes by using these assays in patients undergoing PCI.

9. Future trials should: (i) be large multicenter studies that are realistically powered for ischemic endpoints; (ii) include patients at high risk for stent thrombosis (preferably acute myocardial infarction); (iii) use potent P2Y₁₂ inhibitors such as prasugrel or ticagrelor instead of high-dose clopidogrel to intensify platelet inhibition; and (iv) test the clinical value of other platelet function assays that were not used in previous studies.

10. The cost-effectiveness perspectives of future trials are also going to be highly important, because the balance of the drug-related costs, event-related costs, and the cost of platelet testing should be clearly analyzed in an era when clopidogrel is widely available in generic forms.