Original Title: Randomized Comparison of Different Thienopyridine Loading Strategies in Patients Undergoing Elective Coronary Intervention. The Excelsior LOAD Trial. Reference: Willibald Hochholzer et al. J Am Coll Cardiol Intv. 2016, online before print.

This study assesses how to provide a more rapid antiaggregant effect. It compares the effect of a prasugrel load vs. a 600 mg clopidogrel load, seeing that an effective antiplatelet inhibition at PCI start reduces the risk of ischemic complications.

Clopidogrel administration immediately before PCI provides effective antiaggregation only 2 hours later. Prasugrel has, in theory, the potential to shorten this period.

This study randomly assigned 300 P2Y12 receptor blocker–naive patients undergoing an elective PCI to loading with clopidogrel 600 mg, prasugrel 30 mg, or prasugrel 60 mg immediately before the PCI. Platelet function was assessed serially by impedance aggregometry. The primary endpoint was the proportion of patients with high platelet reactivity defined as ≥468 aggregation units per minute, at 60 min after loading.

At 60 min, 33% of patients assigned to prasugrel 60 mg, 37% of patients assigned to prasugrel 30 mg, and 55% of those assigned to clopidogrel 600 mg had high platelet reactivity (p < 0.001). As from 30 min, prasugrel 60 mg patients achieved significantly lower platelet reactivity than clopidogrel patients. Platelet reactivity at 60 min after prasugrel was not significantly different from that at 120 min after clopidogrel. Prasugrel 30 mg had an intermediate effect. The 30-day incidence of bleeding events was similar in the 3 groups.

Conclusion
As from 30 min, prasugrel 60 mg achieved a stronger platelet inhibition than clopidogrel loading. Compared with clopidogrel, prasugrel 60 mg was associated with a twice as fast onset of platelet inhibition.

Editorial Comment
Patients in this study were stable and PCI was programmed and elective; this is why the slowest onset of platelet inhibition with clopidogrel could be solved by a 600 mg load 2 hours prior procedure. Prasugrel was superior in the short term; however, there is no evidence to support the safety and efficacy of prasugrel followed by clopidogrel maintenance therapy, in this study.