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Monitoring platelet inhibition after clopidogrel with the VerifyNow-P2Y12® rapid analyzer: The VERIfy Thrombosis risk ASsessment (VERITAS) study

https://doi.org/10.1016/j.thromres.2006.01.019Get rights and content

Abstract

Introduction

Clopidogrel inhibits platelet P2Y12 ADP receptors, while ADP, as an inductor of aggregation, stimulates both P2Y12 and P2Y1 platelet receptors. Despite a clinical loading dose routine with clopidogrel, some patients still experience coronary stent thrombosis suggesting persistent platelet activation. The VerifyNow-P2Y12 is a rapid assay that test platelet activity over 3 min and uses of the combination of ADP and prostaglandin E1 (PGE1) to directly measure the effects of clopidogrel on the P2Y12 receptor. ADP is used to maximally activate the platelets by binding to the P2Y1 and P2Y12 platelet receptors, while PGE1 is used to suppress the ADP-induced P2Y1-mediated increase in intracellular calcium levels.

Objective

The VERIfy Thrombosis risk ASsessment (VERITAS) was a prospective study designed to measure platelet response to clopidogrel therapy in subjects with multiple risk factors or history of vascular disease using this novel point-of-care assay.

Methods

166 participants were enrolled in 4 participating sites. Data from 147 participants were analyzed after exclusion of 19 patients due to protocol violations. Platelets were assessed twice at baseline (before clopidogrel) and at 24 h post-loading 450 mg (110 participants) or 7 days after chronic clopidogrel treatment (75 mg/day) (37 patients). All participants received aspirin 81–325 mg for at least 2 days before the study enrollment. Results from the VerifyNow-P2Y12 assay are reported in P2Y12 reaction units (PRU).

Results

Clopidogrel therapy resulted in a mean 64.0 ± 25.3% PRU reduction. No participant reached PRU inhibition below 10% of baseline. Distribution of PRU values for the VerifyNow-P2Y12 assay shows a separation from baseline to post-clopidogrel assay values with some overlap due to high inter-individual variations in response.

Conclusions

VerifyNow-P2Y12 is a reliable, fast and sensitive device suitable for monitoring of platelet inhibition during clopidogrel therapy.

Section snippets

Study population

A study cohort of at least 120 subjects was to be studied on National Committee for Clinical Laboratory Standards (NCCLS) recommendations for reference range calculations [18]. To accomplish this goal, a total of 166 subjects were enrolled in four participating sites. This study was approved by the Institutional Review Board and informed written consent was obtained from each subject before enrollment in the study. Participants eligible for the study had a documented history of vascular disease

Results

One hundred and sixty-six participants were enrolled into the study and 147 of them were considered evaluable. Subjects were considered non-evaluable if any of the following conditions occurred: (1) known interfering substances present at baseline or (2) hematology values outside the institutional or protocol limits. One hundred and ten of the evaluable subjects participated in a single dose study arm (clopidogrel 450 mg) and the remainder (n = 37) was assessed in a repeat dose regimen

Discussion

The VERITAS study demonstrates that the novel VerifyNow-P2Y12 assay is a sensitive device for measuring platelet inhibition with clopidogrel. Both loading and maintenance clopidogrel administration decreased VerifyNow-P2Y12 readings at an average of 64% against baseline, reflecting a corresponding highly significant difference.

Clopidogrel is an effective and specific inhibitor of the P2Y12 ADP receptor. After metabolic activation, the active clopidogrel metabolite irreversibly binds the

Acknowledgements

The authors thank the collaborating nurses and laboratory personnel for their excellent technical assistance in this study. The study was supported in part by a grant from Accumetrics, San Diego, CA, USA, the Aker University Hospital Research Foundation, and the Eastern Regional Health Authority of Norway. These data will be presented in part at the American College of Cardiology Meeting (Atlanta, Georgia, USA, March 11–14, 2006).

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