Variable responsiveness to clopidogrel and aspirin among patients with acute coronary syndrome as assessed by platelet function tests

Unresponsiveness to clopidogrel or aspirin has been reported in patients with acute coronary syndrome (ACS). Platelet aggregometry (PA) and the Impact-R [Cone and Plate(let) Analyzer (CPA) technology, measuring whole blood platelet adhesion under flow conditions] were compared in detecting laboratory unresponsiveness to clopidogrel and aspirin among ACS patients. Platelet-rich plasma (PRP) samples were evaluated in 404 patients by PA using adenosine diphosphate (ADP) and arachidonic acid (AA) and whole blood samples by the Impact-R ADP- and AA-response tests. The first cohort (n=114) was assayed by PA on days 1 and 4 of the onset of ACS. A patient with relative decrease of /=70%. A patient with an absolute value of AA-induced maximal aggregation >/=60% was defined as laboratory NR patient to aspirin. The second cohort (n=290) was tested on day 4 by both systems and results analyzed by receiver operating characteristic curve. The following cut-off values of the Impact-R surface coverage were obtained: 相似文献   

急性脑卒中后伴发全身炎症反应综合征的临床研究

目的探讨急性脑卒中患者全身炎症反应综合征(SIRS)的发生率。方法将338例急性脑卒中患者分为脑出血组(n=126)和脑梗死组(n=212)。采用构成比描述SIRS的发生率,比较各组的差别。结果急性脑卒中患者SIRS的发生率为51.8%,其中出血组的发生率(70.6%)显著高于梗死组(40.6%)(P0.01)。出血组中SIRS的发生率与脑出血量和临床表现严重程度呈正相关,梗死组SIRS的发生率与梗死面积大小呈正相关(P0.01)。结论急性脑卒中常并发SIRS。     

Psychosocial predictors of depression in patients with acute coronary syndrome

OBJECTIVE: To describe the prevalence of depression according to ICD-10 criteria using a self-completed questionnaire and to identify psychosocial predictors of depression at discharge in patients with acute coronary syndrome. METHOD: A total of 899 patients with acute coronary syndrome completed the Major Depression Inventory at discharge and a questionnaire regarding previous depression and family history of depression. Information concerning civil status was obtained from the Civil Person Registry. RESULTS: Ninety patients (10%) were depressed according to ICD-10 criteria at discharge with 7.2% having a moderate to severe depression at discharge. Women were significantly more frequently and severely depressed than men. Patients with and without depression reported primarily somatic symptoms of depression. Cardiovascular risk factors or treatment did not differ between patients with and without depression. Previous depression (OR 2.9, 95% CI 1.4-6.0 adjusted) and female gender (OR 2.5, 95% CI 1.5-4.3 adjusted) predicted depression at discharge in a logistic regression model. CONCLUSION: Somatic symptoms of depression are prevalent in patients with acute coronary syndrome. The use of self-completed non-diagnostic questionnaires assessing symptoms of depression therefore is cautioned as patients may wrongly be identified as depressed. In patients with acute coronary syndrome depression is predicted by well-known psychosocial risk factors.     

Lack of association between the 807 C/T polymorphism of glycoprotein Ia gene and post-treatment platelet reactivity after aspirin and clopidogrel in patients with acute coronary syndrome

Variability in platelet response to antiplatelet therapy and its clinical relevance have been well described. However, the underlying mechanisms remain unclear. It was the aim of the present study to assess whether the response to aspirin and clopidogrel may be influenced by the 807 C/T polymorphism of the glycoprotein Ia (GpIa) gene in patients with non-ST elevation acute coronary syndrome (NSTE ACS). Six hundred one NSTE ACS patients were included in our study and were divided into three groups: CC homozygotes, CT heterozygotes ad TT homozygotes. All patients received loading doses of 600 mg clopidogrel and 250 mg aspirin at least 12 hours before blood samples were drawn. Post-treatment platelet reactivity was assessed by post treatment ADP 10 microM-induced platelet aggregation (ADP-Ag), VASP phosphorylation (PRI VASP) and P-selectin expression. Non-response to dual antiplatelet therapy was defined by high post-treatment platelet reactivity (HPPR=ADP-Ag > 70%). Significant variability in the distribution of platelet parameters was observed in the overall study population. No significant difference in platelet parameters profiles was observed within patients having the same genotype, for ADP-Ag (p=0.33), PRIVASP (p=0.72) and P-selectin expression (p=0.37). The genotype frequencies of the 807 C/T polymorphism of the GpIa gene were similar in responders and non-responders defined by persistent HPPR (p=0.104). In conclusion, our study did not show any influence of 807 C/T polymorphism of GpIa gene on post-treatment platelet reactivity assessed by ADP-Ag, PRI VASP or P-selectin expression in 601 NSTE ACS patients.     

Influence of platelet reactivity and response to clopidogrel on myocardial damage following percutaneous coronary intervention in patients with non-st-segment elevation acute coronary syndrome

Introduction

A wide variability in the response to clopidogrel and magnitude of post-treatment platelet reactivity has been described. However, this has been demonstrated by light transmittance aggregometry, a method too laborious for daily practice. Point-of-care devices may overcome this limitation, but little is known on the predictive value of such measurements. Our objective was to determine the relationship between platelet reactivity and the incidence of myocardial damage following percutaneous coronary intervention (PCI) in patients with Non-ST-segment Elevation Acute Coronary Syndrome (NSTEACS).

Materials and Methods

This prospective study included 93 patients with NSTEACS and PCI. All patients received a loading dose of 300 mg of clopidogrel and 250 mg of aspirin. Myocardial damage was defined as any elevation above upper limit of normal or previous levels of troponin T, assessed every 6 h for at least 24 h following PCI. Platelet reactivity not related to clopidogrel (BASE reactivity), related to P2Y12 inhibition (P2Y12 reactivity) and inhibition of platelet aggregation (IPA) were assessed immediately pre-PCI with the VerifyNow® device.

Results

Myocardial damage was detected in 60 patients (64.5%). Higher BASE reactivity was associated with myocardial damage (287.8 ± 62.6 vs. 260 ± 55.9 units, p = 0.043) while a trend was found for P2Y12 reactivity (173.4 ± 70.3 vs. 149.2 ± 58.4 units, p = 0.109). No relationship was detected for IPA. Multivariate logistic regression analysis confirmed that BASE reactivity (p = 0.04) and P2Y12 reactivity (p = 0.03) were independent predictors of myocardial damage.

Conclusions

Platelet reactivity before PCI appears to be better predictor of myocardial damage than does response to clopidogrel.     

氯吡格雷与阿司匹林联用治疗脑梗死的效果观察

目的观察氯吡格雷联合阿司匹林治疗脑梗死的临床效果。方法选取脑梗死患者70例,随机分为观察组(35例)和对照组(35例),观察组给予氯吡格雷联合阿司匹林治疗,对照组单独给予阿司匹林治疗,观察2组总有效率及治疗前后实验室指标。结果观察组治疗后基本痊愈6例,显效17例,有效10例,总有效率94.29%;对照组基本痊愈2例,显效11例,有效8例,总有效率60.00%,观察组总有效率明显高于对照组,差异有统计学意义(P0.05)。治疗30d后观察组血小板(PLT)、血小板聚集率(PA)及全血黏度(高切、低切)指标均明显低于对照组,差异有统计学意义(P0.05)。结论氯吡格雷联合阿司匹林治疗脑梗死临床效果显著,值得临床推广。     

Hostility and physiological responses to laboratory stress in acute coronary syndrome patients

Objective

Evidence suggests that emotional stress can trigger acute coronary syndromes in patients with advanced coronary artery disease (CAD), although the mechanisms involved remain unclear. Hostility is associated with heightened reactivity to stress in healthy individuals, and with an elevated risk of adverse cardiac events in CAD patients. This study set out to test whether hostile individuals with advanced CAD were also more stress responsive.

Methods

Thirty-four men (aged 55.9±9.3 years) who had recently survived an acute coronary syndrome took part in laboratory testing. Trait hostility was assessed by the Cook Medley Hostility Scale, and cardiovascular activity, salivary cortisol, and plasma concentrations of interleukin-6 were assessed at baseline, during performance of two mental tasks, and during a 2-h recovery.

Results

Participants with higher hostility scores had heightened systolic and diastolic blood pressure (BP) reactivity to tasks (both P<.05), as well as a more sustained increase in systolic BP at 2 h post-task (P=.024), independent of age, BMI, smoking status, medication, and baseline BP. Hostility was also associated with elevated plasma interleukin-6 (IL-6) levels at 75 min (P=.023) and 2 h (P=.016) poststress and was negatively correlated with salivary cortisol at 75 min (P=.034).

Conclusion

Hostile individuals with advanced cardiovascular disease may be particularly susceptible to stress-induced increases in sympathetic activity and inflammation. These mechanisms may contribute to an elevated risk of emotionally triggered cardiac events in such patients.     

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.     

Potent low dose platelet inhibitory effects of clopidogrel and aspirin on coronary thrombus formation in an animal model of acute unstable angina

Application of clopidogrel before percutaneous coronary intervention in patients with acute coronary syndrome reduces the risk of cardiac events. Clopidogrel administration before surgery increases bleeding complications after CABG.Therefore,the antithrombotic effect of the low-dose combination of clopidogrel and aspirin was investigated in an in vivo pig model of coronary artery thrombus formation with cyclic flow reductions.The platelet inhibitory effect was determined by platelet aggregation and CFR, according to the methodology described by Folts. CFR were initiated by endothelial damage and placement of a constrictor around the LAD. 30 min after CFR were established, clopidogrel (0. I mg/kg or 5 mg/kg), aspirin (I mg/kg or 7 mg/kg) or LDC (0. I mg/kg clopidogrel and I mg/kg aspirin) were administered orally. CFR-frequency was determined for further 240 min.CFR-frequency (CFR/30 min) was significantly reduced at 60 min in response to aspirin (7 mg/kg, -48%, p<0.05), and at 120 min in response to clopidogrel (5 mg/kg,-65%, p<0.05) but not at low doses of either compound. In contrast, LDC of clopidogrel (0. I mg/kg) plus aspirin (I mg/kg) resulted in a complete and rapid abrogation of CFR at 90 min (-70%, p<0.05 y. Furthermore, LDC led to reduction of platelet aggregation when CFR-frequency was already significantly decreased. In contrast, high dose groups presented a significant reduction of platelet aggregation prior to CFR-frequency decrease. Low dose combination of clopidogrel plus aspirin demonstrates a potent over additive anti-thrombotic effect in vivo with a significant reduction in thrombus formation early after drug application.The effect occurs before inhibition of platelet aggregation is detectable.     

Frequency and clinical correlates of bipolar features in acute coronary syndrome patients

BackgroundDepression and acute coronary syndrome (ACS) are both extremely prevalent diseases. Studies aimed at evaluating whether depression is an independent risk factor for cardiac events provided no definitive results. In most of these studies, depression has been broadly defined with no differentiation between unipolar (MDD) versus bipolar forms (BD). The aim of this study was to evaluate the frequency of DSM-IV BD (bipolar I and bipolar II subtypes, cyclothymia), as well as temperamental or isolated bipolar features in a sample of 171 patients hospitalized for ACS. We also explored whether these psychopathological conditions were associated with some clinical characteristics of ACS.MethodsPatients with ACS admitted to three neighboring Cardiac Intensive Care Units (CICUs) in a 12-month continuative period of time were eligible for inclusion if they met the criteria for either acute myocardial infarct with or without ST-segment elevation or unstable angina, verified by standard ACS criteria. All patients underwent standardized cardiological and psychopathological evaluations.ResultsOf the 171 ACS patients enrolled, 37 patients (21.7%) were found to have a DSM-IV mood disorder. Of these, 20 (11.7%) had bipolar type I or type II or cyclothymia, while 17 (10%) were the cases of MDD. Rapid mood switches ranged from 11% of ACS patients with no mood disorders, to 47% of those with MDD to 55% of those with BD. Linear regression analysis showed that a diagnosis of BD (p = .023), but not that of MDD (p = .721), was associated with a significant younger age at the index episode of ACS. A history of previous coronary events was more frequent in ACS patients with BD than in those with MDD.ConclusionsOur data indicate that bipolar features and diagnosis are frequent in ACS patients. Bipolar disorder has a negative impact on cardiac symptomatology. Further research in this area is warranted.     

The additive antiplatelet action of clopidogrel in patients with coronary artery disease treated with aspirin

We searched for additional anti-platelet effects of clopidogrel in coronary artery disease (CAD) patients treated with aspirin. Response to clopidogrel was also stratified according to aspirin resistance. Out of 76 screened aspirin-treated CAD male patients, five were aspirin-resistant based on arachidonic acid (AA) and ADP aggregometry. These five patients and 15 aspirin-sensitive patients entered the proper study. Platelet function was assessed at baseline and after one week of additional clopidogrel treatment using aggregometry, flow cytometry (ADP, TRAP-6) and platelet reactivity index (PRI) based on VASP (vasodilatorstimulated phosphoprotein) expression. We evaluated the same markers in 15 healthy men after aspirin treatment. In healthy subjects aspirin did not affect resting or ADP-induced activated GPIIb/IIIa and P-selectin expression. The P-selectin expression on ADP-activated platelets was increased (p < 0.01) in aspirin treated ASA-resistant CAD patients as compared to ASA-sensitive group or aspirin-treated healthy subjects. Clopidogrel significantly decreased ADP and AA-induced platelet aggregation and overcame aspirin resistance in four of five patients. Expression of ADP-induced activation markers was significantly lowered after clopidogrel in all patients. Out of 20 patients, five did not respond to clopidogrel (<10% inhibition of ADP aggregation), and this group showed no change in expression of ADP-induced activation markers after clopidogrel. Clopidogrel treatment significantly reduced PRI only in the clopidogrel-sensitive group. In conclusion, the addition of clopidogrel to aspirin provides greater inhibition of platelets and can overcome aspirin resistance. Flow cytometric analysis of platelets is useful for monitoring of clopidogrel therapy.     

急性脑梗死交感神经皮肤反应检测与临床相关性研究

目的 探讨急性脑梗死患者交感神经皮肤反应(SSR)变化特点及与病情严重程度之间的相关性.方法 将94例急性脑梗死患者分为3组:皮质-皮质下、基底节-丘脑及脑桥组,所有患者均于入院当天进行日常生活能力和临床神经功能缺损(MESSS)评分,并根据瘫痪程度进行分级.于入院3d内行SSR检查,并对检查结果进行分析.结果 (1)急性脑梗死SSR异常率为40.4%,异常率以基底节-丘脑组最高、皮质-皮质下组次之,脑桥组最低;(2)SSR异常率高及波形缺失者,患者肢体瘫痪、临床神经功能缺损程度重、日常生活能力低.SSR异常及波形缺失与瘫痪程度、MESSS评分呈正相关,与BI评分呈负相关.而潜伏期延长、波幅低与瘫痪程度、MESSS及BI评分无关.结论 (1)急性脑梗死后可出现交感神经反射活动的抑制.SSR检测技术可以定量评价急性脑梗死后交感神经的功能状态.(2)SSR异常及波形缺失反映了运动功能受损情况.     

氯吡格雷与阿司匹林联合应用在急性脑梗死治疗中的疗效评定

目的观察急性脑梗死患者血小板上α颗粒膜糖蛋白(CD62p)及溶酶体颗粒膜糖蛋白(CD63)的表达,通过血小板活化的变化,探讨阿司匹林与氯吡格雷联合用药与阿司匹林单药治疗的疗效差异。方法将60例脑梗死患者随机分为两个亚组:单药组(阿司匹林0.15 g/d)和联合用药组(阿司匹林0.10 g/d+氯吡格雷75 mg/d),30例健康体检者为对照组。使用流式细胞术检测所有病例CD62p、CD63阳性率,对单药组和联合用药组治疗前后的CD62p、CD63阳性率进行比较,同时进行NIHSS评分。结果脑梗死组血小板CD62p、CD63阳性率显著高于对照组(P<0.01)。单药组和联合用药组在治疗一周和二周后CD62p、CD63阳性率和NIHSS评分均较治疗前显著下降(P<0.01)。联合用药组治疗二周后与单药组比较CD62p、CD63阳性率和NIHSS评分明显降低,差异有统计学意义(P<0.01)。结论抗血小板治疗对脑梗死有效,阿司匹林+氯吡格雷联合治疗的总体疗效明显优于单用阿司匹林,CD62p、CD63可以衡量抗血小板治疗效果。     

不同剂量氯吡格雷和阿司匹林在急性脑梗死防治中的作用对比

目的比较不同剂量氯吡格雷与阿司匹林在治疗和预防脑梗死中的临床疗效。方法选取2013-01—2015-01我院收治的急性脑梗死患者80例,随机分为氯吡格雷100mg组、氯吡格雷50mg组与阿司匹林组。治疗后对3组临床疗效进行比较,并对3组治疗前后神经功能缺损(NIHSS)评分情况及不良反应发生情况进行观察。结果与阿司匹林组比较,氯吡格雷100mg组与氯吡格雷50mg组临床总有效率均显著提高(P0.05);其中氯吡格雷100mg组显效率较氯吡格雷50mg组显著提高(P0.05);与治疗前比较,3组治疗后NIHSS评分均明显下降,差异均具有统计学意义(P0.05);其中NIHSS评分降低最为显著的是氯吡格雷100mg组,与其他2组比较,差异均有统计学意义(P0.05);3组不良反应发生率比较均无显著性差异(P0.05)。结论氯吡格雷在急性脑梗死治疗和预防中的临床疗效优于阿司匹林,能显著降低神经功能缺损评分,且氯吡格雷100mg临床疗效优于氯吡格雷50mg。     

Clinical, genetic and confounding factors determine the dynamics of the in vitro response/non response to clopidogrel

Platelet inhibition by clopidogrel varies from one individual to the next. Further, in vitro high on-treatment residual adenosine-diphosphate inducible platelet reactivity (HRPR) is associated with an increased risk for major adverse cardiovascular events after percutaneous coronary intervention (PCI) with stent implantation. Recent studies identified numerous influencing factors for the antiplatelet effect of clopidogrel. Besides genetic predispositions, diverse clinical conditions as well as pharmacological interactions were shown to significantly impair clopidogrel-mediated platelet inhibition. Consequently, these influencing factors may affect clinical outcome after PCI and it is therefore desirable to identify cofounders of HRPR by platelet reactivity testing. It is apparent, that not all assays are sensitive to the same variables, and only cofounders of HRPR that are repeatedly identified by more than one test system may be clinically meaningful. However, treatment adjustment based on platelet function testing has not been associated with improved patients' outcome. This summary shall provide an overview over current knowledge on influencing factors for clopidogrel-mediated platelet inhibition and aid guidance for critical interpretation of in vitro obtained data on HRPR.