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Thromb Haemost 2013; 109(02): 347-355
DOI: 10.1160/TH12-06-0378
New Technologies, Diagnostic Tools and Drugs
Schattauer GmbH

Decrease in high on-treatment platelet reactivity (HPR) prevalence on switching from clopidogrel to prasugrel: Insights from the switching anti-platelet (SWAP) study

Jorge F. Saucedo
1   University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, USA
,
Dominick J. Angiolillo
2   University of Florida College of Medicine - Jacksonville, Jacksonville, Florida, USA
,
Roger DeRaad
3   Black Hills Clinical Research Center, Rapid City, South Dakota, USA
,
Andrew L. Frelinger III
4   Children’s Hospital Boston, Harvard Medical School, Boston, Massachusetts, USA
,
Paul A. Gurbel
5   Sinai Center for Thrombosis Research, Baltimore, Maryland, USA
,
Timothy M. Costigan
6   Eli Lilly and Company or a subsidiary, Indianapolis, Indiana, USA
,
Joseph A. Jakubowski
6   Eli Lilly and Company or a subsidiary, Indianapolis, Indiana, USA
,
Clement K. Ojeh
6   Eli Lilly and Company or a subsidiary, Indianapolis, Indiana, USA
,
Suman Duvvuru
6   Eli Lilly and Company or a subsidiary, Indianapolis, Indiana, USA
,
Mark B. Effron
6   Eli Lilly and Company or a subsidiary, Indianapolis, Indiana, USA
,
for the SWAP Investigators › Author Affiliations Financial support:This work was supported by Daiichi Sankyo Company Ltd. and Eli Lilly and Company.
Further Information

Publication History

Received: 06 June 2012

Accepted after major revision: 18 October 2012

Publication Date:
29 November 2017 (online)

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Summary

The prevalence of high platelet reactivity (HPR) in patients who have switched from clopidogrel to prasugrel during maintenance phase after an acute coronary syndrome (ACS) event is unknown. Therefore, the effect of switching from clopidogrel to prasugrel on the prevalence of HPR was evaluated. This analysis from the previously reported SWAP (SWitching Anti Platelet) study assessed HPR at baseline, 2 and 24 hours, and seven days after switching from clopidogrel to prasugrel maintenance dose (MD), with or without a prasugrel loading dose (LD) using four definitions: maximum platelet aggregation (MPA) >65% (primary endpoint), MPA >50%, P2Y12 reaction units (PRU) >235, and platelet reactivity index (PRI) ≥50%. A total of 95 patients were available for analysis; 56 patients provided DNA for genetic assessments of cytochrome P450 (CYP) 2C19. There were 26 (27.4%) patients with HPR at the end of the clopidogrel run-in (defined as MPA >65%). The HPR prevalence varied by each definition and ranged from 19% (PRU >235) to 68% (PRI ≥50%). A significantly higher HPR prevalence was observed during clopidogrel versus the combined prasugrel therapy groups at seven days as measured by MPA >65% (21.2% vs. 4.5%, p>0.05), PRU >235 (18.8% vs. 0%, p=0.001), and PRI ≥50% (66.7% vs. 7.9%, p<0.0001). There was a significantly higher percentage of subjects carrying at least one reduced function allele with HPR measured by MPA >65% (p=0.02) or PRU >235 (p=0.05) than non-carriers with HPR. Switching ACS patients during maintenance clopidogrel therapy to prasugrel with or without an LD is associated with a reduced HPR prevalence and may provide an alternative strategy to treat patients with HPR, independent of CYP2C19 genotype.

Keywords

Clopidogrel - prasugrel - acute coronary syndrome - platelet

* The investigators and centres participating in the SWAP study are listed in the Appendix.


 

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