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 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 μM ADP) and p = 0.003 (20 μM ADP)). There was a strong correlation between MA and FA stimulated by 5 μM (r = 0.84, p < 0.0001) and 20 μM ADP (r = 0.90, p < 0.001). The prevalence of non-responsiveness rose with agonist concentration but did not differ significantly between methods: 5 μM ADP [22% (MA) vs. 17% (FA), p = 0.186] and 20 μM 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 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 P2Y₁₂ inhibitors and support previous studies that employed MA to assess non-responsiveness.