BACKGROUND: Dual therapy with aspirin and clopidogrel has emerged as the gold standard therapy for patients treated with drug-eluting stents (DES). However, there is variability in patients' responses to this antiplatelet therapy, and some patients continue to show ischemic recurrences after therapy. The purpose of the study was to compare the simultaneously obtained results of various platelet-function tests for assessing the prevalence of antiplatelet resistance in coronary artery disease patients undergoing DES therapy. METHODS: A total of 66 patients were administered a loading dose of aspirin, clopidogrel, and cilostazol at least 12 hr before stenting. The results of VerifyNow (Accumetrics, USA), multiplate analyzer (Dynabyte Medical, Germany), and vasodilator-stimulated phosphoprotein/P2Y12 (Biocytex, France) assays were compared with those of light transmission aggregometry (LTA) analysis. RESULTS: The P2Y12 reaction units and P2Y12% inhibition values obtained using the VerifyNow assay showed strong correlation (r) with the results of the LTA analysis. All tests results showed low concordance in defining the antiplatelet resistance in patients, and the degrees of agreement were as follows: 0 for aspirin reaction units; 0.25, P2Y12% inhibition; 0, aspirin-sensitive patients' identification test; 0.21, ADPtest; and 0.14, platelet reactivity index, expressed as the kappa statistics. The prevalence of aspirin and clopidogrel resistances in patients resulted in remarkable variations, from 0% to 22.7% and from 9.1% to 48.5%, respectively. CONCLUSIONS: The clinical usefulness of the different assays for the correct classification of patients in terms of antiplatelet resistance remains unclear. Further studies are required to determine the best method for correlating the occurrences of adverse ischemic events.
Aged ; Aspirin/*administration & dosage ; Coronary Artery Disease/*drug therapy ; Drug Resistance ; Drug Therapy, Combination ; Drug-Eluting Stents ; Female ; Humans ; Male ; Middle Aged ; Platelet Aggregation/drug effects ; Platelet Aggregation Inhibitors/*administration & dosage ; Platelet Function Tests ; Purinergic P2Y Receptor Antagonists/administration & dosage ; Receptors, Purinergic P2Y12/metabolism ; Tetrazoles/administration & dosage ; Ticlopidine/administration & dosage/*analogs & derivatives

PURPOSE: Whether addition of cilostazol is superior to increasing dose of clopidogrel in patients with hyporesponsiveness to chronic clopidogrel therapy is unknown. MATERIALS AND METHODS: We studied 73 patients with hyporesponsiveness to clopidogrel on standard dual antiplatelet therapy for more than 2 weeks. Clopidogrel hyporesponsiveness was defined as percent inhibition of P2Y12 reaction units (PRU) <30% on VerifyNow P2Y12 assay. Patients were randomly assigned to increased dose of clopidogrel (aspirin 100 mg+clopidogrel 150 mg daily: group A, n=38) or to receiving additional cilostazol (aspirin 100 mg+clopidogrel 75 mg+cilostazol 100 mg bid daily: group B, n=35). RESULTS: Baseline percent inhibition of PRU and PRU was similar between 2 groups (13.0+/-10.2% versus 11.8+/-9.7%, p=0.61, and 286.3+/-54.7 versus 295.7+/-53.7, p=0.44, respectively). At follow-up, percent inhibition of PRU was higher and PRU was lower significantly in group B than in group A (38.5+/-17.9% versus 28.3+/-16.6%, p=0.02, and 207.3+/-68.2 versus 241.3+/-76.7, p=0.050, respectively). Among those still showing hyporesponsiveness to clopidogrel at follow-up (21 patients in group A, 10 patients in group B), 12 patients completed further crossover study. Compared to the baseline, magnitude of change in percent inhibition of PRU and PRU showed an improved tendency after the crossover (from 2.7+/-8.7% to 15.8+/-18.4%, p=0.08, and from -18.6+/-58.0 to -61.9+/-84.3, p=0.08). CONCLUSION: Adjunctive cilostazol improved clopidogrel responsiveness better than the higher maintenance dose of clopidogrel in hyporesponsive patients with chronic clopidogrel therapy.
Adult ; Aged ; Blood Platelets/drug effects ; Cross-Over Studies ; Drug Administration Schedule ; Female ; Humans ; Male ; Middle Aged ; Platelet Aggregation Inhibitors/*administration & dosage ; Prospective Studies ; Receptors, Purinergic P2Y12/metabolism ; Tetrazoles/*administration & dosage ; Thrombosis/drug therapy ; Ticlopidine/administration & dosage/*analogs & derivatives ; Time Factors ; Treatment Outcome

BACKGROUNDPlatelet function tests are widely used in clinical practice to guide personalized antiplatelet therapy. In China, the thromboelastography (TEG) test has been well accepted in clinics, whereas VerifyNow, mainly used for scientific research, has not been used in routine clinical practice. The aim of the current study was to compare these two point-of-care platelet function tests and to analyze the consistency between the two tests for evaluating on-clopidogrel platelet reactivity in Chinese acute myocardial infarction patients undergoing percutaneous coronary intervention (PCI).

METHODSA total of 184 patients admitted to Fuwai Hospital between August 2014 and May 2015 were enrolled in the study. On-clopidogrel platelet reactivity was assessed 3 days after PCI by TEG and VerifyNow using adenosine diphosphate as an agonist. Based on the previous reports, an inhibition of platelet aggregation (IPA) <30% for TEG or a P2Y12 reaction unit (PRU) >230 for VerifyNow was defined as high on-clopidogrel platelet reactivity (HPR). An IPA >70% or a PRU <178 was defined as low on-clopidogrel platelet reactivity (LPR). Correlation and agreement between the two methods were analyzed using the Spearman correlation coefficient (r) and kappa value (κ), respectively.

RESULTSOur results showed that VerifyNow and TEG had a moderate but significant correlation in evaluating platelet reactivity (r = -0.511). A significant although poor agreement (κ = 0.225) in identifying HPR and a significantly moderate agreement in identifying LPR (κ = 0.412) were observed between TEG and VerifyNow. By using TEG as the reference for comparison, the cutoff values of VerifyNow for the Chinese patients in this study were identified as PRU >205 for HPR and PRU <169 for LPR.

CONCLUSIONSBy comparing VerifyNow to TEG which has been widely used in clinics, VerifyNow could be an attractive alternative to TEG for monitoring on-clopidogrel platelet reactivity in Chinese patients.

Adenosine Diphosphate ; therapeutic use ; Aged ; Aspirin ; therapeutic use ; Blood Platelets ; drug effects ; China ; Female ; Humans ; Male ; Middle Aged ; Myocardial Infarction ; drug therapy ; surgery ; Percutaneous Coronary Intervention ; methods ; Platelet Aggregation ; drug effects ; Platelet Aggregation Inhibitors ; therapeutic use ; Point-of-Care Systems ; Receptors, Purinergic P2Y12 ; metabolism ; Thrombelastography ; Ticlopidine ; analogs & derivatives ; therapeutic use

BACKGROUND/AIMS: Newer P2Y12 inhibitors, such as prasugrel and ticagrelor, have greater antiplatelet efficacy but may increase the risk of bleeding. In this study, we compared the pharmacodynamic efficacy of prasugrel and ticagrelor in East Asian patients with acute coronary syndrome (ACS). METHODS: We selected 83 ACS patients undergoing percutaneous coronary intervention who were discharged with 90 mg ticagrelor twice daily (n = 24), 10 mg prasugrel daily (n = 39) or 5 mg prasugrel daily (n = 20). After 2 to 4 weeks, on-treatment platelet reactivity (OPR) was assessed in terms of P2Y12 reaction units (PRUs) using the VerifyNow P2Y12 assay (Accumetrics). We compared East Asian (85 < PRU < or = 275) and Caucasian (85 < PRU < or = 208) criteria for assessing the therapeutic window of OPR. RESULTS: OPR was lowest in the ticagrelor group, followed by the 10 mg prasugrel and 5 mg prasugrel groups (49.1 ± 29.9 vs. 83.7 ± 57.1 vs. 168.5 ± 60.8, respectively; p < 0.001). The 5 mg prasugrel group had the highest proportion of patients with OPR values within the therapeutic window, followed by the 10 mg prasugrel and ticagrelor groups (90.0% vs. 46.2% vs. 12.5%, respectively; p < 0.001 for East Asian criteria; 60.0% vs. 43.6% vs. 12.5%, respectively; p < 0.001 for Caucasian criteria). CONCLUSIONS: Short-term administration of 5 mg prasugrel facilitated maintenance within the therapeutic window of OPR compared with the 10 mg prasugrel and ticagrelor groups. Thus, 5 mg prasugrel daily may be the optimal antiplatelet regimen for stabilized East Asian ACS patients.
Acute Coronary Syndrome/blood/diagnosis/ethnology/*therapy ; Adenosine/administration & dosage/adverse effects/*analogs & derivatives/pharmacology ; Aged ; *Asian Continental Ancestry Group ; Blood Platelets/*drug effects/metabolism ; Drug Administration Schedule ; Drug Monitoring/methods ; European Continental Ancestry Group ; Female ; Hemorrhage/chemically induced ; Humans ; Male ; Middle Aged ; *Percutaneous Coronary Intervention/adverse effects ; Pilot Projects ; Platelet Aggregation Inhibitors/administration & dosage/adverse effects ; Platelet Function Tests ; Prasugrel Hydrochloride/administration & dosage/adverse effects/*pharmacology ; Purinergic P2Y Receptor Antagonists/administration & dosage/adverse effects/*pharmacology ; Receptors, Purinergic P2Y12/blood/*drug effects ; Republic of Korea ; Retrospective Studies ; Risk Factors ; Time Factors ; Treatment Outcome