Light Transmittance Aggregometry Induced by Different Concentrations of Adenosine Diphosphate to Monitor Clopidogrel Therapy: A Methodological Study

Light transmission aggregation (LTA) is considered the reference method to identify residual platelet reactivity (RPR) in high-risk patients with coronary artery disease on clopidogrel treatment. An international standardization of this technique is still ongoing and different concentrations of adenosine diphosphate (ADP) as the agonist for LTA have been used to evaluate the inhibitory effect of clopidogrel treatment. To evaluate RPR, LTA was performed using different ADP concentrations (2, 5, 10, and 20 mu mol/L) in 466 high-risk patients with coronary artery disease on dual antiplatelet therapy who underwent percutaneous coronary intervention and in 46 healthy subjects. A VerifyNow P2Y12 assay was assessed as a point-of care system. Imprecision studies showed higher coefficients of variation for LTA by 2 and 5 mu mol/L ADP (healthy subjects: 4.7% and 3.9%; patients: 6.8% and 5.2%, respectively) in comparison with those obtained determining LTA using 10 and 20 mu mol/L ADP (healthy subjects: 2.2% and 2.3%; patients: 2.7% and 3.1%, respectively). In patients, a significant difference (P < 0.0001) between mean values of LTA obtained with all ADP concentrations was found, even if LTA data were significantly correlated (at least: rho = 0.88, P < 0.0001). However, data from 10 and 20 mu mol/L ADP LTA were very similar and highly concordant (k = 95.9%). All agreements were significant (for all P < 0.0001), in particular the agreement between 10 and 20 mu mol/L ADP LTA was very good (k = 0.86, P < 0.0001). A moderate agreement between VerifyNow and both 10 and 20 mu mol/L ADP LTA was observed. LTA by 10 and 20 mu mol/L ADP gave equivalent percentages of aggregation and highly concordant results in terms of RPR in patients with coronary artery disease on clopidogrel. Significant concordant results were observed between both 10 and 20 mu M ADP LTA and VerifyNow. This suggests that a concentration of 10 mu mol/L ADP may be considered adequate for the identification of RPR of patients on clopidogrel and should be preferred for standardization LTA.