Monitoring platelet inhibition after clopidogrel with the VerifyNow-P2Y12(R) rapid analyzer: the VERIfy Thrombosis risk ASsessment (VERITAS) study.
BACKGROUND
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.
Malinin
Alex
A
HeartDrug Research Laboratories, Johns Hopkins University, Baltimore, MD, USA.
Pokov
Alex
A
Spergling
Malcolm
M
Defranco
Anthony
A
Schwartz
Kenneth
K
Schwartz
Dianne
D
Mahmud
Ehtisham
E
Atar
Dan
D
Serebruany
Victor
V
D000244:Adenosine Diphosphate / Q000494:pharmacology; D000328:Adult; D000368:Aged; D000527:Alprostadil / Q000494:pharmacology; D001792:Blood Platelets / Q000378:metabolism; D000077144:Clopidogrel; D003327:Coronary Disease / Q000150:complications / Q000378:metabolism / Q000628:therapy; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D008991:Monitoring, Physiologic / Q000295:instrumentation / Q000379:methods; D010974:Platelet Aggregation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage*; D010979:Platelet Function Tests / Q000295:instrumentation / Q000379:methods; D011446:Prospective Studies; D058910:Purinergic P2 Receptor Agonists; D058919:Purinergic P2 Receptor Antagonists; D058472:Receptors, Purinergic P2Y1; D015607:Stents; D013927:Thrombosis / Q000209:etiology / Q000378:metabolism / Q000517:prevention & control*; D013988:Ticlopidine / Q000008:administration & dosage / Q000031:analogs & derivatives*
C546382:P2RY1 protein, human; D010975:Platelet Aggregation Inhibitors; D058910:Purinergic P2 Receptor Agonists; D058919:Purinergic P2 Receptor Antagonists; D058472:Receptors, Purinergic P2Y1; D000244:Adenosine Diphosphate; D000077144:Clopidogrel; D000527:Alprostadil; D013988:Ticlopidine