2型糖尿病对阿司匹林和氯吡格雷双联抗血小板药物治疗效应的分析

目的:本研究通过前瞻性连续入选在我院因稳定性冠心病行经皮冠状动脉介入治疗(PCI)的患者,分析探讨糖尿病对阿司匹林和氯吡格雷双联抗血小板药物效应的影响。方法:2008年8月至2011年11月前瞻性连续入选稳定性冠心病患者。入院后服用氯吡格雷前测定花生四烯酸(AA)诱导的血小板聚集率和基线二磷酸腺苷(ADP)诱导的血小板聚集率,之后给予氯吡格雷300 mg负荷量口服,继续服用氯吡格雷75 mg/d至1 d后,再次测定服用氯吡格雷后ADP诱导的血小板聚集率。结果:入选了355例稳定性冠心病患者,其中合并2型糖尿病103例,非糖尿病252例。阿司匹林抵抗的发生率18.6%,糖尿病组与非糖尿病组阿司匹林抵抗的发生率未见明显差异(20.4%vs.17.9%,P=0.578),将患者基线特征纳入Logistic回归模型进行校正后结果显示,糖尿病并未增高阿司匹林抵抗的风险(OR=1.3,95%CI=0.7～2.7,P=0.439)。氯吡格雷抵抗的发生率为20.8%;糖尿病组氯吡格雷抵抗的发生率明显高于非糖尿病组(33.0%vs.15.9%,P<0.001);Logistic回归校正后结果显示,糖尿病是氯吡格雷抵抗的独立危险因素(OR=5.7,95%CI=2.9～11.1,P<0.001)。结论:双联抗血小板药物基础上,糖尿病未增高阿司匹林抵抗的风险;但是糖尿病明显增高了氯吡格雷抵抗的风险。     

急性冠脉综合征患者氯吡格雷抵抗的影响因素

目的评价急性冠状动脉综合征(ACS)患者氯吡格雷抵抗的发生情况及其可能的影响因素。方法所有入选患者均给予阿司匹林100mg/d,氯吡格雷负荷剂量300mg及维持量75mg/d,于服氯吡格雷前、服药后24h分别测定二磷酸腺苷(ADP,浓度25#mol/L)诱导的血小板聚集率,计算血小板聚集抑制率〔△A〕。△A≤10%(包括负值)时考虑存在氯吡格雷抵抗。结果102例ACS患者,其中△A≤10%(包括负值)者43例(42.2%),急性非ST段抬高心肌梗死及置入支架患者氯吡格雷抵抗的发生率高。结论ACS和冠状动脉介入治疗后的抗血栓治疗中,部分患者存在氯吡格雷抵抗。其发生与患者的疾病状态及是否置入支架明显相关。     

经皮冠状动脉介入术后氯吡格雷抵抗的临床观察

目的观察因急性冠脉综合征（ACS）行冠状动脉介入治疗（PCI）患者应用氯吡格雷后血小板聚集率的变化及氯吡格雷抵抗的发生情况。方法ACS患者37例,予氯吡格雷负荷量300mg,继予75mg/d维持,在服用氯吡格雷前,服药后2、4、6、24、48h以及服药后30d取血,测定ADP诱导的血小板聚集率,观察血小板聚集率变化并根据抑制程度判断氯吡格雷抵抗发生率。结果给药后2、4、6、24、48h及30d时,氯吡格雷抵抗的发生率分别为62%、46%、32%、38%、49%和43%,氯吡格雷抵抗者用药后血小板抑制率明显低于反应者,其中1例抵抗者出现亚急性支架内血栓形成。结论PCI治疗的部分患者中存在氯吡格雷抵抗。     

老年急性冠状动脉综合征患者氯吡格雷抵抗的影响因素分析

目的 观察不同年龄急性冠状动脉综合征(ACS)患者,服用氯吡格雷后血小板聚集率的变化和氯吡格雷抵抗(CR)的发生情况及其影响因素;观察CR患者在药物剂量增加后血小板聚集率的变化.方法 选择156例ACS患者,分为老年组(116例)和非老年组(40例),所有患者给予口服氯吡格雷75 mg/d,治疗7天后采用光比浊法测定血小板聚集率的变化.选取血小板聚集率变化≤10%的CR患者,1次给予氯吡格雷300 mg口服,观察24 h后血小板聚集率的变化.结果 氯吡格雷治疗后血小板聚集率明显下降,38例患者发生CR,糖尿病患者发生CR比例较高,占43.3%,将药物剂量增加至300 mg后,有21例CR患者的血小板聚集率下降＞10%.结论 服用氯吡格雷治疗后血小板聚集率明显下降,老年人CR发生率为23.3%,CR与糖尿病和药物剂量有关,与年龄无关.     

急性冠状动脉综合征合并2型糖尿病患者冠状动脉介入术后替格瑞洛与氯吡格雷抗血小板疗效及预后

目的应用血栓弹力图(TEG)评价替格瑞洛与氯吡格雷在急性冠状动脉综合征(ACS)合并糖尿病患者经皮冠状动脉介入治疗(PCI)后抗血小板的疗效及预后。方法纳入ACS合并糖尿病行PCI术的患者180例。随机分为两组,氯吡格雷组(n=92)术前接受负荷量阿司匹林300 mg+氯吡格雷300 mg,术后给予阿司匹林100mg/d,氯吡格雷75 mg/d;替格瑞洛组(n=88)术前接受负荷量阿司匹林300 mg+替格瑞洛180 mg,术后给予阿司匹林100 mg/d,替格瑞洛90 mg,每天两次。血栓弹力图检测两组患者PCI术后24 h花生四烯酸(AA)诱导的血小板抑制率和二磷酸腺苷(ADP)诱导的血小板抑制率,观察并比较两组3个月内不良心血管事件及出血等安全性事件。结果替格瑞洛组ADP激活血小板形成最大血凝块强度(MA-ADP),低于氯吡格雷组(34.94%±11.91%比47.16%±14.90%,P0.001)。血小板AA抑制率、ADP抑制率替格瑞洛组明显高于氯吡格雷组(68.24%±22.96%比48.21%±32.91%,58.16%±23.52%比33.34%±26.67%,P0.001)。结论 ACS合并2型糖尿病患者中,替格瑞洛抗血小板聚集的效果明显优于氯吡格雷,可显著降低3个月内心血管终点事件的发生率,不增加出血风险。     

急性冠脉综合征患者氯吡格雷抵抗的相关影响因素分析

目的 分析氯吡格雷抵抗的相关影响因素,观察氯吡格雷抵抗和心血管事件之间的相关性.方法 选取欲行冠状动脉造影检查的119例急性冠脉综合征（ACS）患者,于术前24 h内未使用及使用氯吡格雷治疗7 d后采集肘静脉血,进行血小板聚集率（PA）检测.根据测算的PA值分为氯吡格雷抵抗（CR）组和非氯吡格雷抵抗（NCR）组,分析CR的影响因素.随访3个月,观察心血管事件和CR之间的相关性.结果 119例ACS患者中,氯吡格雷抵抗（CR）组32例（26.9%）,非氯吡格雷抵抗（NCR）组87例（73.1%）,氯吡格雷抵抗发生率为26.9%.合并糖尿病的ACS患者组CR的发生率较高,为59.4%,非糖尿病ACS患者CR的发生率较低,为32.2%（P＜0.01）,置入2枚以上支架组CR的发生率较NCR组高（43.8%比8.0%,P＜0.05）.CR组服药前基础的血小板聚集率为38.22±8.22,与NCR组血小板聚集率53.95±9.42比较差异有统计学意义（P＜0.05）.3个月后随访主要心血管事件可以看出,CR组心血管事件的发生率较NCR组高（12.5%比1.1%）,两者比较差异有统计学意义（P＜0.05）.结论 ACS患者氯吡格雷抵抗的发生率较高,同时影响临床抗血小板治疗的效果.糖尿病人群更易发生氯吡格雷抵抗.另外,置入支架数的增多使患氯吡格雷抵抗的危险性增加.氯吡格雷抵抗影响患者的预后,与心血管事件的发生有很大的相关性.     

氯吡格雷抵抗的影响因素

氯吡格雷和阿司匹林联合应用已经成为急性冠状动脉综合征(ACS)及经皮冠状动脉介入(PCI)术后患者的标准治疗方案,可显著降低死亡或心血管事件的发生率。部分患者尽管长期服用常规剂量的氯吡格雷(300mg负荷量,维持量75mg/d),但临床上仍未能有效地防止血栓事件的发生,且血小板功能检测证实血小板聚集不能被有效抑制,这种现象称为氯吡格雷抵抗。氯吡格雷抵抗反映氯吡格雷抗血小板治疗失败。研究表明,氯吡格雷抵抗可能与血栓事件的复发密切相关,并受基因和非基因因素的影响。     

老年冠心病介入治疗氯吡格雷抵抗的影响因素

目的: 探讨60岁以上老年冠心病患者行冠状动脉介入治疗（percutaneous coronary intervention,PCI）术后氯吡格雷抵抗的发生率和影响因素。方法: 符合入选标准的患者208例,年龄61～80岁,根据对氯吡格雷的反应分为氯吡格雷抵抗组55例和氯吡格雷有反应组153例。 结果: 氯吡格雷抵抗的发生率26.4%。氯吡格雷抵抗组和有反应组血小板聚集率(platelet aggregation rate,PAR)分别为（57±6）%和（35±9）%（P<0.01）。多因素logistic回归分析提示Ⅱ型糖尿病［P=0.037, 优势比（OR）=2.053,95%置信区间1.045-4.034］是氯吡格雷抵抗的影响因素。结论: 60岁以上老年冠心病患者PCI术后氯吡格雷抵抗的发生率26.4%,Ⅱ型糖尿病是氯吡格雷抵抗的影响因素。     

冠心病患者PCI术后氯吡格雷抵抗的发生率及其影响因素

目的：探讨冠心病患者冠状动脉介入治疗术（PCI）后氯吡格雷抵抗的影响因素。方法：159例行PCI术治疗的冠心病患者,术前予氯吡格雷300 mg负荷剂量治疗,术后予75 mg/d持续治疗。测其服药前、术后24 h和术后5 d以5 μmol/L的二磷酸腺苷诱导的血小板最大聚集率。以血小板聚集抑制率≤10%定义为氯吡格雷抵抗,分为氯吡格雷抵抗组（抵抗组,n=48）和对氯吡格雷反应正常组（正常组,n=111）,比较两组临床基本资料、相关常规检查、手术资料,Logistic回归分析氯吡格雷抵抗的独立危险因素。结果：159例患者中发生氯吡格雷抵抗48例,氯吡格雷抵抗发生率为30.2%。两组患者吸烟比例、并发糖尿病、三酰甘油水平的差异均有统计学意义（均P〈0.05）,两组患者手术资料各项参数比较差异无统计学意义。Logistic回归分析结果显示氯吡格雷抵抗的独立危险因素有糖尿病、长期吸烟。三酰甘油水平无统计学意义。结论：糖尿病、长期吸烟是冠心病患者PCI术后发生氯吡格雷抵抗的独立危险因素。     

不同负荷剂量及维持量氯吡格雷对急性冠脉综合征患者氯吡格雷抵抗的影响

目的 评价不同负荷剂量及维持量氯吡格雷对急性冠脉综合征(ACS)患者氯吡格雷抵抗(CR)产生的影响.方法 所有入选患者随机分为4组,即负荷量氯吡格雷300 mg后每日75 mg组(A组)73例,负荷量氯吡格雷300 mg后每日150 mg组(B组)55例,负荷量氯吡格雷600 mg后每日75 mg组(C组)60例,负荷量氯吡格雷300 mg后每日75 mg,同时加用通心络胶囊4粒/次,每日3次组(D组)52例.予服氧吡格雷前、服药后72 h分别测定血小板聚集抑制率.结果 B组、C组CR发生率明显低于A组、D组(P＜0.05);A组、D组血小板聚集率显著高于B组、C组(P＜0.05),而血小板抑制率显著低于B组、C组(P＜0.05).结论 高负荷剂量、高维持剂量氯吡格雷可以降低ACS患者氯吡格雷抵抗的发生.     

合并糖尿病的冠心病患者PCI治疗后氯吡格雷抵抗的影响因素

目的探讨合并糖尿病的冠状动脉粥样硬化性心脏病（冠心病）患者经皮冠状动脉介入（percutaneous coronary intervention,PCI）治疗后氯吡格雷抵抗的影响因素。方法159例行PCI治疗的冠心病患者,其中糖尿病患者56例,非糖尿病患者103例,术前予氯吡格雷300mg负荷剂量治疗,术后予75mg／d持续治疗。测其服药前、术后24h和术后5d以5μmol／L的二磷酸腺苷诱导的血小板最大聚集率。以血小板聚集抑制率≤10％定义为氯吡格雷抵抗。比较两组临床基线资料、相关常规检查、手术资料。Logistic回归分析糖尿病患者氯吡格雷抵抗的独立危险因素。结果糖尿病组发生氯吡格雷抵抗的比例为48．2％,显著高于非糖尿病组的20．4％,差异有统计学意义（P〈0．05）。糖尿病组三酰甘油浓度显著高于非糖尿病组,差异有统计学意义（P〈0．05）。两组其他基线资料比较,差异无统计学意义（P〉0．05）。Logistic回归分析结果显示糖尿病史（年）（β=0．243,OR=1．184,P=0．028）是糖尿病患者氯吡格雷抵抗的独立危险因素。结论合并糖尿病的冠心病患者存在更高的氯吡格雷抵抗比例。糖尿病史（年）是糖尿病患者PCI治疗后发生氯吡格雷抵抗的独立危险因素。     

Platelet function profile post-clopidogrel therapy in patients with type 2 diabetes undergoing coronary stent implantation

Platelet dysfunction contributes to the increased risk of thromboischemic complications after percutaneous coronary intervention (PCI), particularly in type 2 diabetes. Little is known about the effects of glycemic control on platelet reactivity. We assessed adenosine diphosphate-induced platelet aggregation and flow cytometric expression of P-selectin in 90 patients (56 diabetic and 34 nondiabetic patients) undergoing coronary stent implantation after administration of clopidogrel as a potential predictor of poststent complications and its relation to glycemic control. Posttreatment platelet reactivity was significantly elevated in diabetic compared with nondiabetic participants and was associated with smoking, hypercholesterolemia, overweight, and cardiovascular ischemic events. A linear relationship was found between hemoglobin A1c in diabetic patients and platelet reactivity. Both methods (standard aggregometry and P-selectin expression) used for assessment of platelet function were positively correlated. Low responsiveness to clopidogrel detected by posttreatment platelet reactivity is a risk factor for ischemic events after PCI in diabetic patients.     

Impact of the degree of peri-interventional platelet inhibition after loading with clopidogrel on early clinical outcome of elective coronary stent placement.

OBJECTIVES: Our prospective study tested the hypothesis that the 30-day clinical outcome of elective percutaneous catheter intervention (PCI) differs between strata defined by quartiles of platelet aggregation after loading with 600 mg clopidogrel. BACKGROUND: Platelet responses after loading with clopidogrel are highly variable. The impact of this variability on the peri-interventional risk of patients undergoing PCI has not been investigated prospectively. METHODS: Our study included 802 consecutive patients undergoing elective coronary stent placement. Before PCI, patients received a loading dose of 600 mg clopidogrel followed by 75 mg daily. Primary end point was the 30-day composite of death, myocardial infarction, and target lesion revascularization (major adverse cardiac events [MACE]). Platelet aggregation was assessed immediately before PCI by optical aggregometry (5 micromol/l adenosine diphosphate). RESULTS: During 30-day follow-up, 15 patients (1.9%) incurred MACE (3 deaths, 8 myocardial infarctions, 8 target lesion revascularizations). Quartiles of platelet aggregation were <4%, 4% to 14%, 15% to 32%, and >32%. Thirty-day MACE differed significantly (p = 0.034) between quartiles of platelet aggregation. It was 0.5% in the first quartile, 0.5% in the second, 3.1% in the third, and 3.5% in the fourth. Platelet aggregation above the median carried a 6.7-fold risk (95% confidence interval 1.52 to 29.41; p = 0.003) of 30-day MACE. Multivariable logistic regression analysis, including pertinent covariables, confirmed platelet aggregation as a significant independent predictor of 30-day MACE (adjusted odds ratio per 10% increase in platelet aggregation 1.32, 95% confidence interval 1.04 to 1.61; p = 0.026). CONCLUSIONS: The level of platelet aggregation immediately before elective coronary stenting in patients pre-treated with a high loading dose of clopidogrel is correlated with early outcome after the procedure.     

经皮冠状动脉介入术患者的氯吡格雷抵抗和心血管事件

目的：观察因急性冠脉综合征（ACS）行冠状动脉介入治疗（PCI）出现氯吡格雷抵抗及心血管事件的发生情况。方法：因ACS入院患者42例，予氯吡格雷负荷量300mg，继予75mg／d维持，在服用氯吡格雷前，服药后2h、4h、6h、24h、48h和服药后30d取血，测定ADP诱导的血小板聚集率，根据其抑制程度判断是否为氯吡格雷抵抗，观察氯吡格雷抵抗者心血管事件的发生情况。结果：给药后2h、4h、6h、24h、48h和30d时，氯吡格雷抵抗的发生率分别为59．5％、52．4％、38．1％、38．1％、47．6％和41．5％，16例24h时存在氯吡格雷抵抗者有3例出现心血管事件，虽未达统计学差异，但发生率明显高于无抵抗组。结论：PCI治疗的部分患者中存在氯格雷抵抗，并可能与心血管事件发生有关。     

国产和进口氯吡格雷对经皮冠状动脉介入术后血小板功能的影响

目的观察国产氯吡格雷和进口氯吡格雷对冠心病患者经皮冠状动脉介入治疗(PCI)术后血小板功能的影响。方法将450例冠心病患者随机分为2组,其中国产氯吡格雷组230例,进口氯吡格雷组220例。另选健康对照组220例。两治疗组分别于PCI术前3天开始服用氯吡格雷,服用氯吡格雷前、PCI术前、术后10min及PCI术后1周检查血小板聚集率及血小板活化指标。结果冠心病患者血小板聚集率及血小板活化状态较健康对照组明显增高。治疗前国产和进口氯吡格雷组的血小板聚集率及血小板活化指标差异无统计学意义。两治疗组PCI术后10min血小板聚集率及血小板活化状态均较术前明显增高,PCI术后1周两治疗组之间差异无统计学意义。结论PCI术后血小板聚集率及血小板活化状态明显增高,国产和进口氯吡格雷均有良好的抗血小板作用,两者抗血小板聚集和活化的作用相似。     

Clopidogrel resistance response in patients with coronary artery disease and metabolic syndrome: the role of hyperglycemia and obesity

Background Despite the proven benefits of clopidogrel combined aspirin therapy for coronary artery disease (CAD), CAD patients with metabolic syndrome (MS) still tend to have coronary thrombotic events. We aimed to investigate the influence of metabolic risk factors on the efficacy of clopidogrel treatment in patients with CAD undergoing percutaneous coronary intervention (PCI). Methods Cohorts of 168 MS and 168 non-MS subjects with CAD identified by coronary angiography (CAG) were enrolled in our study. MS was defined by modified Adult Treatment Panel III criteria. All subjects had taken 100 mg aspirin and 75 mg clopidogrel daily for more than 1 month, and administered loading doses of 600 mg clopidogrel and 300 mg aspirin before PCI. Blood samples were taken 24 h after the loading doses of clopidogrel and aspirin. Platelet aggregation was measured using light transmittance aggregometry (LTA) and thrombelastography (TEG). Clopidogrel resistance was defined as more than 50% adenosine diphosphate (ADP) induced platelet aggregation as measured by TEG. Results Platelet aggregation inhibition rate by ADP was significantly lower in patients with MS as measured both by TEG (55% ± 31% vs. 68% ± 32%; P < 0.001) and LTA (29% ± 23% vs. 42% ± 29%; P < 0.001). In the multivariate analysis, elderly [OR (95% CI): 1.483 (1.047–6.248); P = 0.002], obesity [OR (95% CI): 3.608 (1.241–10.488); P = 0.018], high fasting plasma glucose level [OR (95% CI): 2.717 (1.176–6.277); P = 0.019] and hyperuricemia [OR (95% CI): 2.583 (1.095–6.094); P = 0.030] were all statistically risk factors for clopidogrel resistance. CAD patients with diabetes and obesity were more likely to have clopidogrel resistance than the CAD patients without diabetes and obesity [75% (61/81) vs. 43% (67/156); P < 0.001]. Conclusions CAD patients with MS appeared to have poorer antiplatelet response to clopidogrel compared to those without MS. Obesity, diabetes and hyperuricemia were all significantly associated with clopidogrel resistance.     

Comparison of higher clopidogrel loading and maintenance dose to standard dose on platelet function and outcomes after percutaneous coronary intervention using drug-eluting stents

Adequate antiplatelet therapy is paramount for good clinical outcomes in patients undergoing percutaneous coronary intervention (PCI). The purpose of this study was to determine whether a high-dose regimen of clopidogrel in patients undergoing PCI is superior to standard dosing. A total of 119 patients undergoing PCI were blindly randomized in 2:1 fashion to receive clopidogrel loading 600 mg on the table immediately before PCI and 75 mg 2 times/day for 1 month (high-dose group) versus standard dosing (300 mg loading and 75 mg/day; low-dose group). Platelet aggregation was measured using light transmission aggregometry at baseline, 4 hours, and 30 days. The composite of cardiovascular death, myocardial infarction, and target vessel revascularization was studied at 30 days in addition to major and minor bleeding. Baseline characteristics and baseline platelet aggregation were similar in the 2 groups. Percent inhibitions of platelet activity were 41% and 27% in the high-dose group versus 19% and 10% in the low-dose group at 4 hours and 30 days (p = 0.046 and 0.047, respectively). Composite clinical end points were 10.3% in the high-dose group and 23.8% in the low-dose group (p = 0.04). No difference was noted in major or minor bleeding. In conclusion, a higher loading and maintenance dose of clopidogrel in patients undergoing PCI results in superior platelet inhibition and decreased cardiovascular events without increasing bleeding complications.     

Aspirin resistance is associated with a high incidence of myonecrosis after non-urgent percutaneous coronary intervention despite clopidogrel pretreatment

OBJECTIVES: We sought to investigate the effect of aspirin resistance on the incidence of myonecrosis after non-urgent percutaneous coronary intervention (PCI) among patients pretreated with clopidogrel. BACKGROUND: Oral antiplatelet therapy using aspirin and a thienopyridine is the standard of care for preventing thrombotic complications of PCI. The effect of aspirin resistance on the outcomes of patients undergoing PCI is unknown. METHODS: We used the Ultegra Rapid Platelet Function Assay-ASA (Accumetrics Inc., San Diego, California) to determine aspirin responsiveness of 151 patients scheduled for non-urgent PCI. All patients received a 300-mg loading dose of clopidogrel >12 h before and a 75-mg maintenance dose in the morning of the PCI. The incidence of myonecrosis was measured by creatine kinase-myocardial band (CK-MB) and by troponin I (TnI) elevations after PCI. RESULTS: A total of 29 (19.2%) patients were noted to be aspirin-resistant. There was a significantly higher incidence of female subjects in the aspirin-resistant versus aspirin-sensitive groups. The incidence of any CK-MB elevation was 51.7% in aspirin-resistant patients and 24.6% in aspirin-sensitive patients (p = 0.006). Elevation of TnI was observed in 65.5% of aspirin-resistant patients and 38.5% of aspirin-sensitive patients (p = 0.012). Multivariate analysis revealed aspirin resistance (odds ratio [OR] 2.9; 95% confidence interval [CI] 1.2 to 6.9; p = 0.015) and bifurcation lesion (OR 2.8; 95% CI 1.3 to 6.0; p = 0.007) to be independent predictors of CK-MB elevation after PCI. CONCLUSIONS: Despite adequate pretreatment with clopidogrel, patients with aspirin resistance as measured by a point-of-care assay have an increased risk of myonecrosis following non-urgent PCI.