Smoking promotes clopidogrel-mediated platelet inhibition in patients receiving dual antiplatelet therapy

Background

High on-treatment residual platelet reactivity is associated with an increased risk of adverse events after coronary stenting. Recent data suggest that cigarette smoking might enhance clopidogrel-mediated platelet inhibition. We therefore sought to investigate the influence of cigarette smoking on clopidogrel- and aspirin-mediated platelet inhibition after percutaneous intervention with stent implantation.

Patients and methods

Platelet aggregation was assessed by the VerifyNow P2Y12 and aspirin assays in 102 patients on dual antiplatelet therapy 24 hours after peripheral, coronary or carotid artery stenting. Among these, there were 33 nonsmokers, 29 former smokers and 40 current smokers. Patients in the fourth quartile of the VerifyNow assays were considered as patients with high on-treatment platelet reactivity.

Results

Current smokers had significantly lower P2Y12 Reaction Units compared with nonsmokers (p = 0.028). Former smokers also had lower adenosine diphosphate (ADP)-inducible platelet aggregation than nonsmokers, but the difference was not significant (p = 0.52). A high on-treatment residual ADP-inducible platelet aggregation was more common among nonsmokers than among current smokers (14 vs 5; p = 0.004). In a multivariate regression analysis smoking was an independent influencing variable for post-treatment ADP-inducible platelet reactivity (p = 0.026). Aspirin-mediated platelet inhibition showed no significant differences between nonsmokers and former smokers or current smokers (p > 0.3).

Conclusion

By in vitro testing, cigarette smoking is associated with enhanced clopidogrel- but not aspirin-mediated platelet inhibition. The clinical implications have to be evaluated in large prospective trials.     

Evidence of increased platelet reactivity in the first six months after acute ST segment elevation myocardial infarction

Introduction

Platelets play a crucial role in the pathogenesis of acute coronary syndromes. Accordingly, previous studies showed increased platelet reactivity on admission in these patients. In this study we assessed platelet reactivity at short-medium term follow-up in patients with ST-segment elevation acute myocardial infarction (STEMI).

Materials and methods

Fifty-nine patients (58 ± 11 years, 45 men), treated with primary angioplasty, were studied 1 month after STEMI. Thirty-five patients were retested at 6 months. Twenty matched patients with stable coronary artery disease served as controls. Platelet reactivity was assessed by flow cyometry at rest and at peak exercise, with and without adenosine diphosphate (ADP) stimulation, by measuring monocyte-platelet aggregates (MPAs) and glycoprotein IIb/IIIa (CD41) expression in the MPA gate, and CD41 and fibrinogen receptor (PAC-1) expression in the platelet gate.

Results

Compared to controls, basal MPAs and CD41 in the MPA gate were higher in STEMI patients both at 1 month (p = 0.001 and p = 0.002, respectively) and at 6 months (p = 0.03 and p = 0.01, respectively). Basal CD41 and PAC-1 expression was also higher in STEMI patients at the two assessments compared to controls (P < 0.001 for both). Exercise induced a similar increase in platelet reactivity in patients and controls. ADP induced a higher increase in CD41 platelet expression in STEMI patients compared to controls both at 1 and 6 months (P < 0.001).

Conclusion

Platelet reactivity is increased in the first 6 months after STEMI. The persistence of increased platelet reactivity in this time period may play a role in the early recurrence of coronary events after STEMI.     

氯吡格雷在急性脑梗死的糖尿病患者中血小板抑制效应的研究

目的用血栓弹力图(thromboelastograms,TEG)评价合并糖尿病的急性脑梗死患者正规使用氯吡格雷后血小板抑制率的变化及氯吡格雷抵抗情况。方法收集住院的急性脑梗死患者80例,其中糖尿病患者33例,非糖尿病患者47例,所有患者予以顿服氯吡格雷负荷量300 mg继以75 mg/d维持,在服用氯吡格雷3 d后和7 d后空腹抽取肘静脉血标本,用血栓弹力图(thromboelastograms,TEG)测定10μmol/L二磷酸腺苷(adenosine diphosphate,ADP)受体途径诱导的血小板抑制率,分析比较两组患者临床特征、血小板抑制率的差异和氯吡格雷抵抗情况。结果糖尿病组的空腹血糖(Fasting plasma glucose,FPG)和糖化血红蛋白(%)显著高于非糖尿病组,差异具有统计学意义(P<0.05)。糖尿病组3 d后和7 d的血小板抑制率显著低于非糖尿病组,差异具有统计学意义(P<0.05)。糖尿病组3 d和7 d后分别有11例(33.3%)、12例(36.4%)患者出现氯吡格雷抵抗的现象,显著高于非糖尿病组的6例(12.8%)、5例(10.6%),差异具有统计学意义(P<0.05)。结论糖尿病患者的血小板抑制率明显低于非糖尿病患者,更容易发生氯吡格雷抵抗现象。     

瑞舒伐他汀联合氯吡格雷对脑梗死急性期患者血小板活化及聚集状态的影响

目的探讨瑞舒伐他汀联合氯吡格雷对脑梗死急性期患者血小板活化及聚集状态的影响。方法脑梗死急性期患者76例,随机分为2组。对照组给予氯吡格雷治疗,观察组给予瑞舒伐他汀联合氯吡格雷治疗。结果治疗后,观察组神经功能缺损评分及疗效优于对照组,差异具有统计学意义(P0.05)。治疗后,观察组CD63表达水平(0.2±0.1)%,CD62P表达水平(1.4±0.8)%均优于对照组(0.4±0.2)%、(2.6±1.0)%,差异有统计学意义(P0.05)%。治疗后,观察组AA水平(83.8±21.2)%及ADP途径诱导的血小板抑制率(50.0±18.1)%高于对照组的(65.5±21.9)%、(37.2±10.4)%,差异有统计学意义(P0.05)。结论瑞舒伐他汀联合氯吡格雷可有效抑制脑梗死急性期患者血小板活化及聚集,促进神经功能损伤恢复。     

Insights into the interpretation of light transmission aggregometry for evaluation of platelet aggregation inhibition by clopidogrel

Introduction

When studying the efficacy of clopidogrel to inhibit platelet aggregation by light transmission aggregometry, technical decisions must be taken prior to assessment or during analysis, including, but not limited to, concentration of agonist to use and timing of the evaluation of the response on the aggregation curve obtained (peak ADP-stimulated platelet aggregation vs. late aggregation). We investigated how some of these technical modalities affected the results of platelet aggregation obtained after clopidogrel administration.

Materials and methods

One hundred and twenty stable coronary artery disease patients requiring a diagnostic angiography were recruited prior to pre-treatment with clopidogrel. Blood samples were tested before clopidogrel initiation and immediately preceding coronary angiography using light transmission aggregometry with either 5 or 20 µM of ADP. Aggregation was measured at maximal amplitude (peak), and 5 minutes after agonist addition (late).

Results

While measurements of platelet aggregation as either peak or late aggregation were strongly correlated, peak platelet aggregation was significantly higher than late aggregation, by 10.8% and by 10.3% with ADP 5 and 20 µM, respectively. Moreover, the use of ADP 20 µM resulted in less spontaneous disaggregation than 5 µM in the absence of clopidogrel (11.8% and 4.8% with ADP 5 µM and 20 µM, respectively).

Conclusions

When assessing platelet aggregation following clopidogrel, measurement of late aggregation after addition of ADP 20 µM should be preferred. Large clinical trials should be conducted to assess which parameter between residual aggregation or inhibition of platelet aggregation by clopidogrel best predicts clinical efficacy of the drug.     

Genetic determinants of high on-treatment platelet reactivity in clopidogrel treated Chinese patients

Introduction

Cytochrome P450 (CYP), ATP-binding cassette transporters (ABCB1), and paraoxonase-1 (PON1) play crucial roles in clopidogel absorption and bioactivation. Genetic polymorphisms in these genes have been associated with the variability of the response to clopidogrel, however their contribution to high on-treatment platelet reactivity (HPR) in clopidogrel treated Chinese patients is less known.

Materials and methods

Five-hundred Chinese-Han patients treated with clopidogrel for acute coronary syndrome (ACS) were consecutively recruited from the Department of Geriatric Cardiology, General Hospital of Chinese People’s Liberation Army, from September 2010 to September 2012. We assessed the relations of CYP2C19*2 (rs4244285), CYP2C19*3 (rs4986893), CYP2C19*17 (rs12248560), PON1Q129R (rs662) and ABCB1C3435T (rs1045642) to the platelet aggregation after 5 days maintenance dose of clopidogrel administration, and the risk for HPR. The cutoff of HPR was defined as 20 μmol/L adenosine diphosphate (ADP)-induced platelet aggregation > 50%.

Results

Both CYP2C19*2 and *3 alleles were significantly associated with higher platelet aggregation after 5 days maintenance dose of clopidogrel administration (P < 0.00001and P = 0.042, respectively). The platelet aggregation in carriers of at least one CYP2C19 loss-of-function allele (*2 or *3, accounted for 58% of the study population) was obviously higher than that in non-carriers (P < 0.00001). Patients with the CYP2C19*2 allele had a higher risk of HPR than those with the CYP2C19 wild-type genotype [adjusted hazard ratio (HR), 1.56; 95% confidence interval(CI), 1.04–2.33, P = 0.03]. The carriers of at least one CYP2C19 loss-of-function allele could also predict significantly greater risk of HPR compared with non-carriers (adjusted HR1.79,95% CI: 1.33–2.4,P = 0.003). However, the carriage of CYP2C19*3 alone could not predict the risk of HPR significantly (adjusted HR, 1.5; 95% CI: 0.83–3, P = 0.16). Significant relation of CYP2C19*17, PON1Q129R and ABCB1C3435T to the platelet aggregation was not found.

Conclusion

In clopidogrel treated Chinese patients with ACS, carriers of at least one CYP2C19 loss-of-function allele could predict greater risk of HPR, with the impact mainly attributing to CYP2C19*2. Neither ABCB1 nor PON1 genotype could influence the antiplatelet response of clopidogrel in the cohort of Chinese patients.     

急性脑梗死患者氯吡格雷抵抗的相关因素研究

目的 探讨急性脑梗死患者氯吡格雷抵抗(clopidogrel resisitance,CR)的相关因素。方法 收集急性脑梗死患者100例,入院后连续口服氯吡格雷7 d后空腹抽取肘静脉血,用血栓弹力图(thromboelastograms,TEG)测得二磷酸腺苷(adenosine diphosphate,ADP)受体途径诱导的血小板抑制率,将患者分为氯吡格雷抵抗组(CR)和氯吡格雷敏感组(clopidogrel sensitivity,CS); 根据2组患者的临床检测水平和Logistic回归分析引起CR的因素。结果 31例患者出现氯吡格雷抵抗,发生率为31%。单因素分析发现并发2型糖尿病、LDL-C水平、空腹血糖水平(FPG)差异明显(P<0.05)。多因素Logistic回归分析发现,2型糖尿病(OR=13.198,P<0.05)、LDL-C水平(OR=0.349,P<0.05)是引起CR的独立危险因素。结论 部分急性脑梗死患者会出现氯吡格雷抵抗,2型糖尿病、LDL-C水平是其独立危险因素。     

脑梗死患者血小板计数与体积的变化

目的　脑梗死患者血小板计数与体积的变化。方法　随机选择 10 0例脑梗死患者测定血小板数目与体积 ,2 1例健康人作为正常对照组。结果　脑梗死患者的MPV均普遍大于正常对照组 (P <0 0 1) ,而PLT低于正常对照组 (P <0 0 5 )。大面积脑梗死MPV大于小面积及腔隙性梗死 (P <0 0 1)。腔隙性梗死PLT高于小面积及大面积梗死 (P <0 0 1)。结论　在脑梗死患者中 ,血小板计数与体积的变化具有显著性意义 ,值得进一步研究。     

脑梗死急性期血小板超微结构的变化及意义

目的：探讨脑梗死急性期血小板超微结构的变化及其意义,方法：采用透射电镜对20例脑梗死急性期患者的血小板进行观察,结果：发病后24小时内的血小板超微结构改变明显,表现为伪足增多,聚集融合成片状;α颗粒明显减少;线粒体也显著减少,残留者肿胀,空泡化;血小板膜多处破裂;血小板病变的严重程度与脑梗死病灶的大小相一致。发病后2周血小板超微结构明显恢复,但3例面积脑梗 者未见恢复。结论脑梗死急性期血小板超微结构发生明显改变,尤其是α颗粒明显减少,可作为判断病情轻重及预后的一个客观指标。     

Lack of association between the P2Y12 receptor gene polymorphism and platelet response to clopidogrel in patients with coronary artery disease

INTRODUCTION: Clopidogrel inhibits the ADP subtype P2Y(12) receptor. Recently, polymorphisms of this receptor have been associated with different degrees of platelet aggregation in healthy volunteers and have been suggested to modulate clopidogrel response. However, the role of gene sequence variations of the P2Y(12) receptor in patients treated with clopidogrel has not yet been assessed. MATERIALS AND METHODS: The T744C polymorphism of the P2Y(12) receptor gene was assessed in 119 patients: 36 undergoing coronary stenting receiving a 300 mg loading dose (Group A) and 83 on long-term clopidogrel (75 mg/day) treatment (Group B). Patients were divided into 2 subgroups according to the presence or absence of the C allele: carriers (CT heterozygotes and CC homozygotes) and non-carriers (TT homozygotes). Platelet aggregation, assessed by light transmittance aggregometry following ADP, collagen, TRAP and epinephrine stimuli, and platelet activation (GP IIb/IIIa activation and P-selectin expression), assessed by whole blood flow cytometry in ADP and TRAP-stimulated platelets, were performed. Platelet function was assessed at baseline and 4 and 24 h following clopidogrel loading dose in Group A and when patients where on clopidogrel treatment for at least 1 month in Group B. RESULTS: The genotype distribution of Group A was: 22/36 (61.1%) non-carriers and 14/36 (38.9%) carriers of the C allele; Group B: 57/83 (68.7%) non-carriers and 26/83 (31.3%) carriers of the C allele. There were no differences between groups for all the assessed platelet function assays. CONCLUSIONS: The T744C polymorphism of the P2Y(12) receptor gene does not modulate platelet response to clopidogrel either in the early or long-term phases of treatment. This specific gene polymorphism alone is therefore unlikely to be the cause of variability in individual response to antiplatelet therapy.     

Impaired bioavailability of clopidogrel in patients with a ST-segment elevation myocardial infarction

Recent data has indicated that interindividual variability of intestinal absorption is an important determinant of the wide response variability to clopidogrel. We hypothesised that the physiological state of STEMI influences the intestinal absorption of clopidogrel. To evaluate this, we determined the pharmacokinetic response to a high loading dose of clopidogrel and the absolute ADP induced change in aggregation from baseline in STEMI patients and healthy volunteers. We found a significantly impaired bioavailability in STEMI patients as compared to healthy volunteers and a strong correlation between the reduction in platelet aggregation and the maximal plasma concentration of the active metabolite of clopidogrel. Although large clinical trails have clearly demonstrated the effectiveness of clopidogrel in the setting of STEMI, this small observational study encourages further research based on clinical endpoints to define the optimal dosing of clopidogrel in STEMI patients.     

脑梗塞患者血小板数目,体积和功能的变化

目的研究脑梗塞患者血小板数目，体积和功能变化。方法随机选择９７例脑梗塞患者测定急性期和恢复期血小板数目，体积，粘附和聚集功能，３０例健康人作为正常对照组。结果脑梗塞急性期血小板体积，粘附率和聚集率均高于对照组（Ｐ＜０．０１）；而血小板数目和解聚率均低于对照组（Ｐ＜０．０１）。恢复期血小板体积，粘附率，５分钟聚集率虽比急性期降低，但仍高于对照组（Ｐ＜０．０１），而血小板数目及解聚率与对照组相似。大面积梗塞血小板，粘附率和最大聚集率均高于小面积梗塞（Ｐ＜０．０１）；多元逐步回归分析血小板体积，最大聚集率与脑梗塞容积呈正相关。结论脑梗塞患者血小板消耗，体积增大，功能亢进，血小板体积与最大聚集率和梗塞面积有关     

N端脑钠肽前体对急性心肌梗死并发脑梗死的预测价值

目的探讨N端脑钠肽前体(NT-proBNP)对急性心肌梗死(acute myocardial infarction,AMI)患者并发脑梗死的预测作用。方法回顾分析了445例AMI患者的临床资料,全部患者均在首次胸痛24 h内测定血浆NT-proBNP水平。通过受试者工作曲线(receiver operating characteristic curve,ROC)分析NT-proBNP预测脑梗死发生的价值及界值,并通过Logistic回归分析比较NT-proBNP的独立预测价值。结果AMI后1年内共有29例患者并发脑梗死。脑梗死组发病24 h内血浆NT-proBNP水平明显高于无脑梗死组(P<0.05)。ROC曲线显示NT-proBNP有可能预测脑梗死的发生。根据ROC曲线定1082 ng/L为最佳分界值时,预测AMI患者并发脑梗死的敏感性、特异性、准确度、阳性和阴性预测值分别为50.0%、96.8%、84.3%、52.1%、96.5%。Logistic回归分析显示NT-proBNP水平﹥1082 ng/L是AMI并发脑梗死的独立危险因素。结论发病24 h内血浆NT-proBNP水平﹥1082 ng/L的AMI患者易并发脑梗死。     

氯吡格雷联合拜阿司匹林治疗老年急性脑梗死疗效观察

目的 探讨氯吡格雷联合拜阿司匹林治疗老年急性脑梗死的疗效和安全性.方法 120例急性脑梗死随机分为三组.治疗组40例,氯吡格雷组40例,拜阿司匹林组40例.在常规治疗基础上,治疗组加用氯吡格雷和拜阿司匹林,氯吡格雷组加用氯吡格雷,拜阿司匹林组加用拜阿司匹林治疗.治疗14d后,观察三组用药前后疗效及安全性.结果 治疗组能明显改善脑梗死局灶神经功能缺损症状(P＜0.05),疗效优于氯吡格雷组和拜阿司匹林组;三组对出凝血指标无明显影响(P＞0.05).结论 氯吡格雷联合拜阿司匹林治疗急性脑梗死安全有效,并能明显改善急性脑梗死患者的局灶神经功能缺损症状,效果优于单独应用氯吡格雷或拜阿司匹林.     

氯吡格雷对急性脑梗死患者血浆溶血磷脂酸水平的影响

目的研究急性脑梗死患者血浆溶血磷脂酸(Lysophosphatidic acid,LPA)水平的变化及氯吡格雷对急性脑梗死患者血浆溶血磷脂酸水平的影响,探求急性脑梗死有效的干预方法。方法所有脑梗死患者随机分为氯吡格雷组及实验对照组,氯吡格雷组除给予脑梗死常规治疗外,加用氯吡格雷75mgqdpo,实验对照组只给予常规治疗。对急性脑梗死患者分别在治疗前、治疗3d及21d后进行血浆LPA水平的检测。结果氯吡格雷组治疗前及治疗21d后血浆LPA水平为:(4.82±1.10)和(2.23±0.96)μmol/L,两者相比有显著性差异(P<0.01);实验组治疗前及治疗21d后血浆LPA水平为(4.79±1.24)和(3.26±1.20)μmol/L,2者相比差异有显著性(P<0.01),两组治疗21d后血浆LPA水平相比差异有显著性(P<0.01)。皮层支氯吡格雷组治疗前及治疗21d后血浆LPA水平为:(5.59±1.08)和(2.62±1.03)μmol/L,2者相比差异有显著性(P<0.01);皮层支实验对照组治疗前及治疗21d后血浆LPA水平为:(5.55±0.96)和(4.01±0.75)μmol/L,2者相比差异有显著性(P<0.01),两组治疗21d后血浆LPA水平相比差异有显著性(P<0.01)。深穿支氯吡格雷组治疗前及治疗3d后血浆LPA水平为:(3.98±1.02)和(2.77±0.98)μmol/L,2者相比差异有显著性(P<0.01);深穿支实验对照组治疗前及治疗3d后血浆LPA水平分别为:(3.95±1.17)和(3.83±1.56)μmol/L,2者相比差异无显著性(P>0.01),两组治疗3d后血浆LPA水平相比差异有显著性(P<0.01)。结论氯吡格雷可降低急性脑梗死患者血浆LPA水平,对皮层支及深穿支梗死均有效,深穿支效果更佳。     

缺血性卒中患者因氯吡格雷低反应性改为高维持量及替格瑞洛后血小板抑制率变化

目的探讨用血栓弹力图评价符合双抗治疗的缺血性脑血管病患者,因氯吡格雷低反应性,改为高维持剂量及改服替格瑞洛后血小板抑制率的变化。方法选择符合双抗治疗的缺血性脑血管病患者联合应用抗血小板制剂(阿司匹林肠溶片100 mg/qd+氯吡格雷75 mg/qd)前及后7 d,用血栓弹力图检测患者的花生四烯酸(AA)和二磷酸腺苷(ADP)途径诱导的血小板抑制率,筛选出氯吡格雷低反应性者96例,随机分为3组,常规剂量组(氯吡格雷75 mg/qd,32例)、高维持量组(氯吡格雷150 mg/qd,32例)和替格瑞洛组(替格瑞洛90 mg/bid,32例),3组阿司匹林继续按原剂量服用。分组后3组按新方案治疗7 d,再次复查血栓弹力图。结果分组后高维持量组及替格瑞洛组ADP诱导的血小板抑制率较常规剂量组有显著性差异(P0.05),3组均未发生出血等严重不良事件,替格瑞洛组发生1例轻度呼吸困难。替格瑞洛组高于同一时间点高维持量组ADP途径诱导的血小板抑制率(P0.05)。结论针对常规剂量氯吡格雷的低反应性,替格瑞洛及双倍剂量的氯吡格雷均能有效降低血小板的高反应性,并且替格瑞洛的作用更为明显,且未增加出血等不良事件的发生。     

阿司匹林与氯吡格雷双联对TIA患者凝血功能的影响

目的探讨阿司匹林与氯吡格雷双联对短暂性脑缺血发作(TIA)患者血小板聚集率和纤维蛋白原的影响。方法100例短暂性脑缺血发作患者随机分为2组,在常规控制血压、血糖、血脂等基础上,治疗组给予阿司匹林联合氯吡格雷治疗,对照组给予阿司匹林,其中阿司匹林100mg/d,氯吡格雷75mg/d。观察2组血小板聚集率与纤维蛋白原相关指标及临床疗效。结果治疗7~14d后,与对照组比较,治疗组血小板聚集率显著改善(P0.05),纤维蛋白原水平下降更显著(P0.05);治疗组临床疗效显著优于对照组(P0.05)。2组均未出现严重出血并发症。结论阿司匹林与氯吡格雷双联治疗短暂性脑缺血发作可改善患者血小板聚集率,降低纤维蛋白原水平,临床疗效显著。     

金纳多对急性脑梗死患者血小板聚集和血液流变学的影响

目的 :观察金纳多对脑梗死患者血小板聚集和血液流变学的影响。方法 :将 6 8例急性脑梗死患者随机分为两组 ,金纳多治疗组 38例 ,对照组 30例 ,对两组患者检测治疗前后血小板聚集和血液流变学各指标并进行神经功能缺损评分。结果 :金纳多治疗组显效率为 89 5 % ,对照组为 76 7% (P <0 0 5 )。金纳多治疗后血粘度、纤维蛋白原、红细胞电泳时间、血小板第一时相聚集率 (Ⅰ°M)、血小板第二时相聚集率 (Ⅱ°M)均降低 ,明显优于对照组 (P <0 0 5 )。结论 :金纳多通过拮抗血小板聚集和改善血液流变学而对急性脑梗死具有治疗作用     

Follow-up of patients with acute myocardial infarction treated with intravenous streptokinase

The sequel of survivors after hospitalisation for an acute myocardial infarction was studied during the following 15 years in 48 patients treated with streptokinase and in 41 controls. No significant difference was seen in the morbidity or mortality during the first 6 months nor in the mortality thereafter.     

Monitoring platelet inhibition after clopidogrel with the VerifyNow-P2Y12(R) rapid analyzer: the VERIfy Thrombosis risk ASsessment (VERITAS) study

INTRODUCTION: Clopidogrel inhibits platelet P2Y12 ADP receptors, while ADP, as an inductor of aggregation, stimulates both P2Y12 and P2Y1 platelet receptors. Despite a clinical loading dose routine with clopidogrel, some patients still experience coronary stent thrombosis suggesting persistent platelet activation. The VerifyNow-P2Y12 is a rapid assay that test platelet activity over 3 min and uses of the combination of ADP and prostaglandin E1 (PGE1) to directly measure the effects of clopidogrel on the P2Y12 receptor. ADP is used to maximally activate the platelets by binding to the P2Y1 and P2Y12 platelet receptors, while PGE1 is used to suppress the ADP-induced P2Y1-mediated increase in intracellular calcium levels. OBJECTIVE: The VERIfy Thrombosis risk ASsessment (VERITAS) was a prospective study designed to measure platelet response to clopidogrel therapy in subjects with multiple risk factors or history of vascular disease using this novel point-of-care assay. METHODS: 166 participants were enrolled in 4 participating sites. Data from 147 participants were analyzed after exclusion of 19 patients due to protocol violations. Platelets were assessed twice at baseline (before clopidogrel) and at 24 h post-loading 450 mg (110 participants) or 7 days after chronic clopidogrel treatment (75 mg/day) (37 patients). All participants received aspirin 81-325 mg for at least 2 days before the study enrollment. Results from the VerifyNow-P2Y12 assay are reported in P2Y12 reaction units (PRU). RESULTS: Clopidogrel therapy resulted in a mean 64.0+/-25.3% PRU reduction. No participant reached PRU inhibition below 10% of baseline. Distribution of PRU values for the VerifyNow-P2Y12 assay shows a separation from baseline to post-clopidogrel assay values with some overlap due to high inter-individual variations in response. CONCLUSIONS: VerifyNow-P2Y12 is a reliable, fast and sensitive device suitable for monitoring of platelet inhibition during clopidogrel therapy.