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

INTRODUCTIONTicagrelor is a novel antiplatelet drug developed to reduce atherothrombosis. The PLATO trial compared ticagrelor and aspirin to clopidogrel and aspirin in patients with acute coronary syndromes (ACS). Ticagrelor was found to be superior in the primary composite endpoint of cardiovascular death, myocardial infarction or stroke, without increasing major bleeding events. The current study estimates the lifetime cost-effectiveness of ticagrelor relative to generic clopidogrel from a Singapore public healthcare perspective.

METHODSThis study used a two-part cost-effectiveness model. The first part was a 12-month decision tree (using PLATO trial data) to estimate the rates of major cardiovascular events, healthcare costs and health-related quality of life. The second part was a Markov model estimating lifetime quality-adjusted survival and costs conditional on events during the initial 12 months. Daily drug costs applied were SGD 1.05 (generic clopidogrel) and SGD 6.00 (ticagrelor). Cost per quality-adjusted life years (QALY) was estimated from a Singapore public healthcare perspective using life tables and short-term costs from Singapore, and long-term costs from South Korea. Deterministic and probabilistic sensitivity analyses were performed.

RESULTSTicagrelor was associated with a lifetime QALY gain of 0.13, primarily driven by lower mortality. The resulting incremental cost per QALY gained was SGD 10,136.00. Probabilistic sensitivity analysis indicated that ticagrelor had a > 99% probability of being cost-effective, given the lower recommended WHO willingness-to-pay threshold of one GDP/capita per QALY.

CONCLUSIONBased on PLATO trial data, one-year treatment with ticagrelor versus generic clopidogrel in patients with ACS, relative to WHO reference standards, is cost-effective from a Singapore public healthcare perspective.

Acute Coronary Syndrome ; drug therapy ; economics ; Adenosine ; analogs & derivatives ; economics ; therapeutic use ; Aspirin ; administration & dosage ; Clinical Trials as Topic ; Cost-Benefit Analysis ; Decision Trees ; Drug Costs ; Humans ; Markov Chains ; Platelet Aggregation Inhibitors ; administration & dosage ; economics ; Purinergic P2Y Receptor Antagonists ; administration & dosage ; economics ; Quality-Adjusted Life Years ; Republic of Korea ; Singapore ; Ticlopidine ; administration & dosage ; analogs & derivatives

BACKGROUND/AIMS: Impaired responsiveness to clopidogrel is common in patients with type 2 diabetes mellitus (DM). The aim of this study was to evaluate the clinical application of a point-of-care assay to detect impaired responsiveness to clopidogrel after coronary stent implantation in patients with type 2 DM. METHODS: We measured P2Y12 reaction units (PRU) with the VerifyNow point-of-care assay in 544 consecutive patients undergoing dual or triple (i.e., dual plus cilostazol) anti-platelet therapy after coronary stent implantation. High platelet reactivity (HPR) was defined as a PRU value > or = 240. RESULTS: The mean PRU values were 233.5 +/- 83.2 and 190.3 +/- 85.5 in patients undergoing dual or triple anti-platelet therapy, respectively (p < 0.001). Patients with DM manifested higher post treatment PRU values (238.3 +/- 82.4 vs. 210.8 +/- 86.8, p = 0.001) and a higher frequency of HPR (44.8% vs. 31.0%, p = 0.003) as compared to patients without DM. We also found that higher PRU values and a higher frequency of HPR were present in patients with DM who were undergoing both triple and dual anti-platelet therapy. However, the higher post-treatment PRU values observed in patients with DM decreased with triple anti-platelet therapy (219.4 +/- 82.5 vs. 247.9 +/- 81.1, p = 0.044). CONCLUSIONS: A point-of-care assay can detect elevated platelet reactivity and impaired responsiveness to clopidogrel in patients with type 2 DM. The addition of cilostazol to dual anti-platelet therapy may decrease post-treatment PRU values in patients with type 2 DM.
Aged ; Angioplasty, Balloon, Coronary/adverse effects/*instrumentation ; Aspirin/administration & dosage ; Chi-Square Distribution ; Coronary Disease/blood/*therapy ; Diabetes Mellitus, Type 2/*blood ; Drug Therapy, Combination ; Female ; Humans ; Logistic Models ; Male ; Middle Aged ; Platelet Activation/*drug effects ; Platelet Aggregation Inhibitors/*administration & dosage/adverse effects ; *Platelet Function Tests ; *Point-of-Care Systems ; Predictive Value of Tests ; Purinergic P2Y Receptor Antagonists/*administration & dosage/adverse effects ; Registries ; Republic of Korea ; Risk Assessment ; Risk Factors ; *Stents ; Tetrazoles/*administration & dosage/adverse effects ; Ticlopidine/administration & dosage/adverse effects/*analogs & derivatives ; Treatment Outcome

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