Ticagrelor vs. Clopidogrel in Ad Hoc PCI
What are the pharmacodynamic (PD) effects of ticagrelor versus clopidogrel loading dose (LD) in the periprocedural period among troponin-negative acute coronary syndrome (ACS) patients undergoing ad hoc percutaneous coronary intervention (PCI)?
This was a prospective, open-label, randomized, multicenter, parallel-group, phase IV PD study. One hundred P2Y12 inhibitor-native patients presenting with biomarker-negative ACS and undergoing ad hoc PCI, on a background of aspirin therapy, were randomized to receive either ticagrelor 180 mg LD or clopidogrel 600 mg LD. Platelet reactivity (P2Y12 reaction units [PRUs]; VerifyNow assay) was measured at 5 time points: pre-LD, at 0.5, 2, and 8 hours post-LD, and at the end of PCI. The primary endpoint was PRU levels 2 hours post-LD; secondary endpoints included PRU levels at all other time points and inhibition of platelet aggregation; an exploratory analysis evaluated rates of high on-treatment platelet reactivity (HPR; PRU >208).
At 2 hours, PRU levels were significantly lower with ticagrelor versus clopidogrel (98.4 ± 95.4 vs. 257.5 ± 74.5, p < 0.001; primary endpoint). PRU levels diverged as early as 0.5 hour post-LD, with significant differences observed by the end of PCI (mean 0.6 hour post-LD) and maintained up to 8 hours post-LD. HPR rates were also significantly reduced with ticagrelor compared with clopidogrel at the end of PCI (p = 0.030), and at 2 hours (p < 0.001) and 8 hours (p < 0.001) after LD.
The authors concluded that among low-risk ACS patients undergoing ad hoc PCI, ticagrelor LD provides more prompt and potent platelet inhibition, and lower HPR rates, compared with clopidogrel LD.
This study reports that compared with clopidogrel LD, ticagrelor LD was associated with more prompt platelet inhibitory effects, more potent antiplatelet effects, and reduced rates of HPR. Overall, the results suggest that ticagrelor LD is more effective than clopidogrel LD for inhibition of platelet reactivity in the peri-intervention period in low-risk, troponin-negative ACS patients undergoing ad hoc PCI. Additional prospective studies with hard clinical endpoints are needed to establish whether the PD benefits of ticagrelor translate into improved outcomes in this cohort.
Keywords: Acute Coronary Syndrome, Aspirin, Biological Markers, Adenosine, Blood Platelets, Percutaneous Coronary Intervention, Platelet Aggregation, Platelet Function Tests, Ticlopidine, Troponin
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