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Thromb Haemost 2012; 107(02): 338-345
DOI: 10.1160/TH11-09-0622
Platelets and Blood Cells
Schattauer GmbH

Inter-patient variability and impact of proton pump inhibitors on platelet reactivity after prasugrel

Dániel Aradi
1   University of Pécs, Heart Institute, Division of Interventional Cardiology, Hungary
,
Wiktor Kuliczkowski
2   3rd Department of Cardiology, Medical University of Silesia, Katowice, Poland
,
Dan Atar
3   Department of Cardiology, Oslo University Hospital Ulleväl and Institute for Clinical Medicine, University of Oslo, Oslo, Norway
,
Victor L. Serebruany
4   HeartDrug™ Research LLC, Johns Hopkins University, Towson, Maryland, USA
› Author Affiliations Financial support: The study was supported in part by Sanofi-Aventis, and HeartDrug Research LLC.
Further Information

Publication History

Received: 12 September 2011

Accepted after major revision: 28 October 2011

Publication Date:
29 November 2017 (online)

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Summary

Although there is considerable variability of platelet reactivity among patients treated with clopidogrel, little is known about inter-individual differences and possible role of proton pump inhibitors (PPIs) after prasugrel. We defined the extent of inter-patient variability, and evaluated the impact of PPI interaction in prasugrel-treated patients with acute coronary syndrome (ACS). Between January 2010 and May 2011, 104 prospective, high-risk patients with ACS were recruited into this multicentre, prospective, observational study. Twelve to 24 hours after receiving 60 mg loading dose of prasugrel, light transmission aggregometry (LTA) and whole blood impedance aggregometry (Multiplate) were used to assess platelet activity. Platelet function measurements were repeated during maintenance phase on reduced (5 mg) or on conventional (10 mg) doses of prasugrel. High platelet reactivity (HPR) was defined according to the consensus document of the Working Group on High On-Treatment Platelet Reactivity (LTA:>46%; Multiplate:>47U). Compared to maintenance doses, 60 mg loading dose of prasugrel provided significantly greater platelet reactivity inhibition (p<0.05). There were no significant differences between the conventional and reduced maintenance doses. Notably, a remarkable inter-patient variability was present in platelet reactivity after all doses of prasugrel, and the prevalence of HPR was significantly higher during the maintenance doses (p<0.05). Although median platelet reactivity values were consistently higher when prasugrel was used in combination with PPIs, these differences were not significant (p≥0.17). Despite potent platelet inhibition, inter-patient variability is present after all tested doses of prasugrel. The 60 mg loading dose is superior to conventional and reduced maintenance doses in terms of platelet reactivity inhibition and regarding the prevention of HPR.

Keywords

ADP receptors - antiplatelet agents - antiplatelet drugs - platelet pharmacology

 

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