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Thromb Haemost 2015; 114(05): 1020-1027
DOI: 10.1160/TH15-03-0257
Cellular Haemostasis and Platelets
Schattauer GmbH

Temporal variability in the antiplatelet effects of clopidogrel and aspirin after elective drug-eluting stent implantation

An ADAPT-DES substudy
Thomas G. Nührenberg
1   Universitäts-Herzzentrum Freiburg • Bad Krozingen, Klinik für Kardiologie und Angiologie II, Bad Krozingen, Germany
,
Christian Stratz
1   Universitäts-Herzzentrum Freiburg • Bad Krozingen, Klinik für Kardiologie und Angiologie II, Bad Krozingen, Germany
,
Stefan Leggewie
1   Universitäts-Herzzentrum Freiburg • Bad Krozingen, Klinik für Kardiologie und Angiologie II, Bad Krozingen, Germany
,
Willibald Hochholzer
1   Universitäts-Herzzentrum Freiburg • Bad Krozingen, Klinik für Kardiologie und Angiologie II, Bad Krozingen, Germany
,
Christian M. Valina
1   Universitäts-Herzzentrum Freiburg • Bad Krozingen, Klinik für Kardiologie und Angiologie II, Bad Krozingen, Germany
,
Michael Gick
1   Universitäts-Herzzentrum Freiburg • Bad Krozingen, Klinik für Kardiologie und Angiologie II, Bad Krozingen, Germany
,
Ajay J. Kirtane
2   Columbia University Medical Center and the Cardiovascular Research Foundation, New York, New York, USA
,
Gregg W. Stone
2   Columbia University Medical Center and the Cardiovascular Research Foundation, New York, New York, USA
,
Franz-Josef Neumann
1   Universitäts-Herzzentrum Freiburg • Bad Krozingen, Klinik für Kardiologie und Angiologie II, Bad Krozingen, Germany
,
Dietmar Trenk
1   Universitäts-Herzzentrum Freiburg • Bad Krozingen, Klinik für Kardiologie und Angiologie II, Bad Krozingen, Germany
3   Institut für Pharmazeutische Wissenschaften, Albert-Ludwigs-Universität, Freiburg, Germany
› Author Affiliations Financial support: The ADAPT-DES platelet function study was sponsored by the Cardiovascular Research Foundation, New York, NY, USA, under a US Food and Drug Administration investigational device exemption. The study was funded by research grants from Boston Scientific, Abbott Vascular, Medtronic, Cordis, Biosensors, The Medicines Company, Daiichi-Sankyo, Eli Lilly, Volcano, and Accumetrics.

Clinical Trial Registration. http://www.clinicaltrials.gov NCT00638794.
Further Information

Publication History

Received: 26 March 2015

Accepted after major revision: 17 June 2015

Publication Date:
06 December 2017 (online)

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Summary

Given conflicting data on temporal variability in pharmacodynamic platelet responses to clopidogrel, we investigated platelet reactivity on clopidogrel and aspirin for up to six months after elective percutaneous coronary intervention (PCI) with drug-eluting stents. Platelet reactivity was determined in 102 patients before loading with clopidogrel and aspirin, and on maintenance therapy after PCI on day 1, at one month and six months by VerifyNow™ P2Y12 and Aspirin assays and by residual platelet aggregation (RPA) on light transmission aggregometry using adenosine diphosphate and arachidonic acid. By VerifyNow testing, median (interquartile range) P2Y12 reaction units (PRU) on clopidogrel were 166 (90–234), 195 (124–257), and 198 (141–252) on day 1, one month and six months after PCI, respectively (p=0.005 day 1 to 1 month, and p=0.86 1 month to 6 months). Using a cut-off of > 208 PRU, 35% of patients had high platelet reactivity (HPR) to clopidogrel on day 1, 43% at one month, and 46% at six months after PCI. Between day 1 and six months after PCI, 38.2% of patients changed clopidogrel responder status at least once. Other cut-offs and RPA yielded similar results. Platelet inhibition by aspirin was consistent over time with only five patients being characterised as having HPR. Considerable variation in individual on-clopidogrel platelet reactivity was present during both the subacute and the late phases of maintenance therapy after elective PCI. Hence, the utility of contemporary platelet function testing to guide antiplatelet therapy may be limited.

Keywords

Clopidogrel - platelet reactivity - VerifyNow™ - ADAPT-DES - drug-eluting stent

 

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