Prasugrel Overcomes High On-Clopidogrel Platelet Reactivity Post-Stenting More Effectively Than High-Dose (150-mg) Clopidogrel: The Importance of CYP2C19*2 Genotyping

Dimitrios Alexopoulos; Gerasimos Dimitropoulos; Periklis Davlouros; Ioanna Xanthopoulou; George Kassimis; Eleana F. Stavrou; George Hahalis; Aglaia Athanassiadou

doi:10.1016/j.jcin.2010.12.011

JACC: Cardiovascular Interventions

Volume 4, Issue 4, April 2011 DOI: 10.1016/j.jcin.2010.12.011

Prasugrel Overcomes High On-Clopidogrel Platelet Reactivity Post-Stenting More Effectively Than High-Dose (150-mg) Clopidogrel
The Importance of CYP2C192* Genotyping

Dimitrios Alexopoulos, Gerasimos Dimitropoulos, Periklis Davlouros, Ioanna Xanthopoulou, George Kassimis, Eleana F. Stavrou, George Hahalis and Aglaia Athanassiadou

Author + information

vol. 4 no. 4 403-410

DOI:

https://doi.org/10.1016/j.jcin.2010.12.011

Published By:

JACC: Cardiovascular Interventions

Print ISSN:

1936-8798

Online ISSN:

1876-7605

History:

Received October 13, 2010
Accepted December 26, 2010
Published online April 1, 2011.

American College of Cardiology Foundation

Author Information

Dimitrios Alexopoulos, MD^⁎,^⁎ (dalex{at}med.upatras.gr),
Gerasimos Dimitropoulos, MD^⁎,
Periklis Davlouros, MD^⁎,
Ioanna Xanthopoulou, MD^⁎,
George Kassimis, MD^⁎,
Eleana F. Stavrou, PhD^†,
George Hahalis, MD^⁎ and
Aglaia Athanassiadou, PhD^†

^⁎
^†

↵⁎Reprint requests and correspondence:
Dr. Dimitrios Alexopoulos, Department of Cardiology, Patras University Hospital, Rion 26500 Patras, Greece

Abstract

Objectives The primary aim of the study was to determine the antiplatelet effects of prasugrel versus high-dose clopidogrel in patients with high on-treatment platelet reactivity (HTPR) after percutaneous coronary intervention (PCI) and, secondarily, their relation to cytochrome (CYP) 2C19*2 carriage.

Background High on-treatment platelet reactivity after clopidogrel administration after PCI is linked to the loss-of-function CYP2C19*2 allele and accompanied by an increased risk of adverse events.

Methods We performed a prospective, randomized, single-blind, crossover study of platelet inhibition by prasugrel 10 mg/day versus high-dose 150 mg/day clopidogrel in 71 (of 210 screened; 33.8%) post-PCI patients with HTPR. Platelet function was assessed by the VerifyNow assay (Accumetrics, San Diego, California), and real-time polymerase chain reaction genotyping was performed for CYP2C19*2 carriage.

Results The primary endpoint of platelet reactivity (measured in platelet reactivity units) at the end of the 2 treatment periods was lower after prasugrel compared with clopidogrel (least-squares estimates 129.4, 95% confidence interval [CI]: 111.1 to 147.7 versus 201.7, 95% CI: 183.2 to 220.2; p < 0.001). The least-squares mean difference between the 2 treatments was −122.9 (95% CI: −166.7 to −79.2, p < 0.001), and −47.5 (95% CI: −79.5 to −15.4, p = 0.004), in carriers and noncarriers of at least 1 mutant allele, respectively. The HTPR rates were lower for prasugrel than for clopidogrel, in all patients (7.5% vs. 35.8%, p < 0.001), in carriers (5.3% vs. 47.4%, p = 0.007), and in noncarriers (8.8% vs. 29.4%, p = 0.005), respectively.

Conclusions In patients with HTPR after PCI, prasugrel is more effective compared with high clopidogrel in reducing platelet reactivity, particularly in CYP2C19*2 carriers. Genotyping guidance might be helpful only in case an increased clopidogrel maintenance dose is considered. (Prasugrel Versus High Dose Clopidogrel in Clopidogrel Resistant Patients Post Percutaneous Coronary Intervention (PCI); NCT01109784)

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