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ExcelsiorLOAD: Prasugrel superior to clopidogrel for platelet inhibition in stable patients undergoing PCI
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Prasugrel 60 mg was associated with faster and more effective platelet inhibition compared with clopidogrel in stable patients undergoing PCI, according to new findings.
Researchers performed the ExcelsiorLOAD randomized trial to determine to what extent administering prasugrel (Effient, Daiichi Sankyo/Eli Lilly) before PCI is more effective than administering clopidogrel before PCI in terms of platelet inhibition.
They randomly assigned 300 stable patients undergoing PCI who had never before taken a P2Y12 inhibitor (mean age, 68 years; 80% men) to be loaded with clopidogrel 600 mg, prasugrel 30 mg or prasugrel 60 mg immediately before PCI. The groups had similar clinical and angiographic characteristics.
The primary endpoint was percentage of patients with high on-treatment platelet reactivity, defined as at least 468 aggregation units (AU) x min, at 60 minutes after loading.
Lower reactivity with prasugrel
At 60 minutes after preloading, 33% of patients assigned prasugrel 60 mg had high on-treatment platelet reactivity vs. 37% assigned prasugrel 30 mg and 55% of those assigned clopidogrel (P < .001 for prasugrel 60 mg vs. clopidogrel; P = .008 for prasugrel 30 mg vs. clopidogrel; P = .024 for prasugrel 60 mg vs. prasugrel 30 mg), according to the results.
At any time point from 30 minutes onward, prasugrel 60 mg was associated with significantly lower platelet reactivity compared with clopidogrel, Hochholzer and colleagues wrote. Using platelet reactivity as a continuous variable did not change the results.
Platelet activity with prasugrel 60 mg at 60 minutes was similar to platelet activity with clopidogrel at 120 minutes (P = .18).
The incidence of bleeding events at 30 days did not differ among the three groups, they wrote.
“This strategy [of preloading with prasugrel 60 mg] achieves within 1 hour a similar effect as the full effect of loading with clopidogrel,” Willibald Hochholzer, MD, from University Heart Center Freiburg – Bad Krozingen, department of cardiology and angiology II, Bad Krozingen, Germany, and colleagues wrote. “Although definite proof for the safety and efficacy of this regimen in stable disease is lacking, it might be considered as an option for ad-hoc PCI, particularly in high-risk settings.”
Clinical impact research needed
In a related editorial, Dominick J. Angiolillo, MD, PhD, and Francesco Franchi, MD, both from University of Florida College of Medicine – Jacksonville, wrote: “The major strength of this study is that this is the first to prospectively assess the effects of prasugrel [loading dose], administered after coronary angiography, in patients with stable CAD undergoing ad-hoc PCI, showing a remarkable reduction in [high on-treatment platelet reactivity] rates and platelet reactivity.”
Angiolillo, a member of the Cardiology Today’s Intervention Editorial Board, and Franchi concluded that the study “provides important [pharmacodynamics] data showing that a [loading dose] of prasugrel achieves prompt, potent and predictable antiplatelet effects in the peri-PCI period among stable CAD patients. However, the clinical impact of this strategy needs to be defined in studies adequately powered for safety and efficacy.”– by Erik Swain
Disclosure: Hochholzer reports receiving lecture fees from Boehringer Ingelheim, Bristol-Myers Squibb and Daiichi Sankyo. Two other researchers report financial ties with AstraZeneca, Bayer, Daiichi Sankyo, Eli Lilly and Otsuka. Angiolillo reports financial ties with Abbott Vascular, AstraZeneca, CeloNova, CSL Behring, Daiichi Sankyo, Eli Lilly, Gilead Sciences, GlaxoSmithKline, Janssen Pharmaceuticals, Johnson & Johnson, Merck, Novartis, Osprey Medical, PLx Pharma, St. Jude Medical and The Medicines Company. Franchi reports no relevant financial disclosures.
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