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 vasoditator-stimulated phosphoprotein phosphorylation levels has been used to indicate the extent of P2Y12 blockade. Objectives: 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 PM ADP) and p=0.003 (20 mu M ADP)). There was a strong correlation between MA and FA stimulated by 5 mu M (r=0.84, p < 0.0001) and 20 mu M ADP (r=0.90, p < 0.001). The prevalence of non-responsiveness rose with agonist concentration but did not differ significantly between methods: 5 mu M ADP [22% (MA) vs. 17% (FA), p = 0. 186] and 20 mu M 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. Conclusion: Clopidogrel responsiveness is higher when measured by FA as compared to