Ticagrelor Versus Prasugrel in Acute Coronary Syndrome Patients With High On-Clopidogrel Platelet Reactivity Following Percutaneous Coronary Intervention: A Pharmacodynamic Study

Study Questions:

What is the comparative antiplatelet action of ticagrelor with prasugrel in acute coronary syndrome (ACS) patients with high on-clopidogrel treatment platelet reactivity (HTPR) after percutaneous coronary intervention (PCI)?


In a prospective, single-center, single-blind study, 44 (of 139 screened, 31.7%) ACS patients with HTPR 24 hours post-PCI were randomized to either ticagrelor 90 mg twice daily or prasugrel 10 mg once daily for 15 days with a crossover directly to the alternate treatment for another 15 days. HTPR was defined as platelet reactivity units (PRUs) ≥235, as assessed by the VerifyNow P2Y12 function assay.


The primary endpoint of platelet reactivity at the end of the two treatment periods was lower for ticagrelor (32.9 PRU; 95% confidence interval [CI], 18.7-47.2) compared with prasugrel (101.3 PRU; 95% CI, 86.8-115.7) with a least squares mean difference of –68.3 PRU (95% CI, –88.6 to –48.1; p < 0.001). The secondary endpoint of HTPR rate was 0% for ticagrelor and 2.4% for prasugrel (1/42, p = 0.5). No patient exhibited a major bleeding event at either treatment group.


The authors concluded that in patients with ACS, exhibiting HTPR 24 hours post-PCI, ticagrelor produces a significantly higher platelet inhibition compared with prasugrel.


This direct pharmacodynamic comparison of ticagrelor with prasugrel in ACS patients exhibiting HTPR post-PCI, suggests that ticagrelor provides stronger than prasugrel platelet inhibition. However, both agents effectively treated the phenomenon of HTPR in the study population. Additional prospective studies with hard clinical endpoints are needed to elucidate whether the pharmacodynamic difference observed between the agents translates into differences in clinical efficacy or safety.

Clinical Topics: Acute Coronary Syndromes, Invasive Cardiovascular Angiography and Intervention, Noninvasive Imaging, Interventions and ACS, Interventions and Imaging, Angiography, Nuclear Imaging

Keywords: Acute Coronary Syndrome, Cross-Over Studies, Platelet Aggregation Inhibitors, Coronary Angiography, Thiophenes, Piperazines, Blood Platelets, Hemorrhage, Purinergic P2Y Receptor Antagonists, Percutaneous Coronary Intervention

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