Intensifying P2Y12 Inhibitor Treatment Does Not Abolish Risk Associated With High-on Treatment Platelet Reactivity After Percutaneous Coronary Intervention

Background:
High on treatment platelet reactivity (HPR) during treatment with clopidogrel has been consistently found to be strong risk factor for recurrent ischemic events after PCI. Insufficient P2Y12 receptor inhibition contributes to HPR measured by the VerifyNow (VN) assay, in part due to variation in clopidogrel bioactivation. Prasugrel and ticagrelor are more potent P2Y12 inhibitors than clopidogrel and commonly substituted for clopidogrel when HPR is documented.

Methods:
We identified patients who had undergone platelet reactivity testing after PCI with VN after pretreatment with clopidogrel (n=242) in a single center observational analysis. HPR was defined as PRU>208. Primary clinical endpoint was 1-year post PCI combined cardiovascular death, myocardial infarction (MI), and stent thrombosis.

Results:
One hundred fifty (35%) subjects had HPR and were switched to prasugrel (n=51) and ticagrelor (n=44). Risk of recurrent 1-year MACE was highest among HPR patients switched to ticagrelor, as compared to prasugrel and remained higher than subjects who had low on treatment platelet reactivity (LPR) who remained on clopidogrel (12.5% vs 6.7% vs. 2.8%, p=0.004)(Fig).

Conclusions:
The increased risk of recurrent events associated with HPR measured by VN is not completely attenuated by switching to more potent P2Y12 inhibitors. Non-P2Y12 mediated pathways likely contribute to increased incidence of thrombotic events after PCI in subjects with HPR.