Prasugrel Compared With High Loading- and Maintenance-Dose Clopidogrel in Patients With Planned Percutaneous Coronary Intervention

Abstract

Background-The increasing use of higher-than-approved doses of clopidogrel in clinical practice is based in part on the desire for greater levels of inhibition of platelet aggregation (IPA). Prasugrel is a new thienopyridine that is more potent than standard-dose clopidogrel in healthy subjects and patients with stable coronary artery disease. The relative antiplatelet effects of prasugrel versus high-dose clopidogrel in percutaneous coronary intervention patients are unknown. Methods and Results-Prasugrel in Comparison to Clopidogrel for Inhibition of Platelet Activation and Aggregation-Thrombolysis in Myocardial Infarction 44 (PRINCIPLE-TIMI 44) was a randomized, double-blind, 2-phase crossover study of prasugrel compared with high-dose clopidogrel in patients undergoing cardiac catheterization for planned percutaneous coronary intervention. The primary end point of the loading-dose phase (prasugrel 60 mg versus clopidogrel 600 mg) was IPA with 20 mol/L ADP at 6 hours. Patients with percutaneous coronary intervention entered the maintenance-dose phase, a 28-day crossover comparison of prasugrel 10 mg/d versus clopidogrel 150 mg/d with a primary end point of IPA after 14 days of either drug. In this study, 201 subjects were randomized. IPA at 6 hours was significantly higher in subjects receiving prasugrel (meanϮSD, 74.8Ϯ13.0%) compared with clopidogrel (31.8Ϯ21.1%; PϽ0.0001). During the maintenance-dose phase, IPA with 20 mol/L ADP was higher in subjects receiving prasugrel (61.3Ϯ17.8%) compared with clopidogrel (46.1Ϯ21.3%; PϽ0.0001). Results were consistent across all key secondary end points; significant differences emerged by 30 minutes and persisted across all time points. Conclusions-Among patients undergoing cardiac catheterization with planned percutaneous coronary intervention, loading with 60 mg prasugrel resulted in greater platelet inhibition than a 600-mg clopidogrel loading dose. Maintenance therapy with prasugrel 10 mg/d resulted in a greater antiplatelet effect than 150 mg/d clopidogrel.

Infarct Size Following Treatment With Second‐ Versus Third‐Generation P2Y 12 Antagonists in Patients With Multivessel Coronary Disease at ST‐Segment Elevation Myocardial Infarction in the CvLPRIT Study

“…Indeed, clopidogrel typically achieves a maximum of only 50% platelet inhibition in combination with aspirin in acute coronary syndromes compared with ≈90% with prasugrel and aspirin26 and ≈94% with ticagrelor and aspirin 27. This remains the case even when the larger 600‐mg clopidogrel loading dose is administered 22, 25.…”

World Heart Federation expert consensus statement on antiplatelet therapy in East Asian patients with ACS or undergoing PCI

“…Compared with clopidogrel, administration of prasugrel results in faster and greater platelet inhibition, owing to rapid and efficient generation of the active metabolite, with less patient-to-patient variation. 8,17,18 Ticagrelor is a nonthienopyridine, direct-acting, oral antagonist that binds reversibly to the P2Y 12 receptor ( Figure 1). The major metabolite of ticagrelor (AR-C124910XX), formed by metabolism via CYP3A4, is as potent as the parent compound ticagrelor.…”

How to manage prasugrel and ticagrelor in daily practice

“…In patients scheduled for percutaneous coronary intervention, inhibition of platelet aggregation is significantly greater in patients receiving prasugrel than those receiving clopidogrel, both at 6 h after a loading dose (mean ± SD, 75 ± 13% vs 32 ± 21%) and during maintenance doses (61 ± 18% vs 46 ± 21%) [17]. Although prasugrel metabolism is less influenced by known cytochrome genetic polymorphisms, a large variability in biological responsiveness is still present [8], and HPR can be present in up to 25% of ACS patients who in turn showed an increased incidence of ischaemic events at one month on from percutaneous coronary intervention (PCI) [18].…”