Assessment of clopidogrel responsiveness: measurements of maximum platelet aggregation, final platelet aggregation and their correlation with vasodilator-stimulated phosphoprotein in resistant patients.
BACKGROUND
Controversy surrounds the optimal platelet aggregation measurement to assess clopidogrel non-responsiveness. The P2Y12 reactivity ratio (PRR) determined by vasodilator-stimulated phosphoprotein phosphorylation levels has been used to indicate the extent of P2Y(12) blockade.


OBJECTIVE
We sought to compare the prevalence of non-responsiveness measured by maximum (MA) and 6 min aggregation (FA) and correlate these measurements with PRR in patients with non-responsiveness.


METHODS
MA and FA were measured in stented patients (n=100) before and after clopidogrel treatment. The PRR was determined in 22 non-responsive patients. Responsiveness was defined as pre-treatment minus post-treatment aggregation; and non-responsiveness was defined as <10% change in platelet aggregation.


RESULTS
Responsiveness was greater as determined by FA, p=0.006 (5 microM ADP) and p=0.003 (20 microM ADP)). There was a strong correlation between MA and FA stimulated by 5 microM (r=0.84, p<0.0001) and 20 microM ADP (r=0.90, p<0.001). The prevalence of non-responsiveness rose with agonist concentration but did not differ significantly between methods: 5 microM ADP [22% (MA) vs. 17% (FA), p=0.186] and 20 microM ADP [33% (MA) vs. 29% (FA), p=0.270]. PRR correlated with both MA (r=0.66, p<0.001) and FA (r=0.74, p<0.001) in non-responsive patients indicating incomplete receptor blockade.


CONCLUSIONS
Clopidogrel responsiveness is higher when measured by FA as compared to MA. However, these measurements are equivalent in determining the prevalence of non-responsiveness: FA and MA are affected to the same degree in patients with non-responsiveness. These findings are relevant to ongoing studies assessing platelet inhibition by P2Y(12) inhibitors and support previous studies that employed MA to assess non-responsiveness.
Gurbel
Paul A
PA
Sinai Center for Thrombosis Research, Baltimore, Maryland 21215, USA. PGURBEL@LIFEBRIDGEHEALTH.ORG
Bliden
Kevin P
KP
Etherington
Amena
A
Tantry
Udaya S
US
D000244:Adenosine Diphosphate / Q000494:pharmacology; D000368:Aged; D015815:Cell Adhesion Molecules / Q000032:analysis*; D000077144:Clopidogrel; D004351:Drug Resistance; D005260:Female; D006801:Humans; D008297:Male; D008840:Microfilament Proteins / Q000032:analysis*; D008875:Middle Aged; D010750:Phosphoproteins / Q000032:analysis*; D010766:Phosphorylation; D010974:Platelet Aggregation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology; D058919:Purinergic P2 Receptor Antagonists; D058925:Receptors, Purinergic P2Y12; D013988:Ticlopidine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D013997:Time Factors; D000098662:Vasodilator-Stimulated Phosphoprotein
D015815:Cell Adhesion Molecules; D008840:Microfilament Proteins; C548576:P2RY12 protein, human; D010750:Phosphoproteins; D010975:Platelet Aggregation Inhibitors; D058919:Purinergic P2 Receptor Antagonists; D058925:Receptors, Purinergic P2Y12; D000098662:Vasodilator-Stimulated Phosphoprotein; D000244:Adenosine Diphosphate; D000077144:Clopidogrel; D013988:Ticlopidine