中国汉族老年急性冠脉综合征患者氯吡格雷抗血小板治疗反应性的药物基因组学相关分析

目的 探讨影响中国汉族老年急性冠脉综合征患者氯吡格雷抗血小板反应性的药物基因组学关联因素.方法 严格按照病例纳入和排除标准,连续募集201 1年9月1日至2012年9月1日期间,在解放军总医院住院诊断为急性冠脉综合征的60岁以上患者,并给予常规氯吡格雷和阿司匹林双联抗血小板治疗.采用光密度比浊法检测患者服用稳定剂量氯吡格雷后第5日的腺苷二磷酸(ADP)诱导的血小板聚集率.采用SnapShot基因分型法检测氯吡格雷的代谢和作用通路上的候选相关基因变异型(包括PON1Q192R,CYP2C19*2,CYP2C19*3,CYP2C19*17以及ABCB1 C3435T).结果 在246例符合入选标准的老年急性冠脉综合征患者中,单因素相关分析显示,在候选的氯吡格雷代谢和作用相关基因变异型中,仅有CYP2C 19*2基因型与氯吡格雷稳定治疗后的血小板反应性显著相关(P=0.001),其中CYP2C19*2携带者口服稳定剂量氯吡格雷第5日时ADP诱导的血小板聚集率(46.1％±21.25％)显著高于非携带者(39.38％±19.44％,P＜ 0.001).利用多元逐步回归分析,经校正年龄、性别、体质量指数、合并疾病和合并用药等临床环境相关因素后,CYP2C19*2仍与患者稳定剂量治疗下的血小板聚集率密切相关,它能够解释22.2％的氯吡格雷抗血小板反应性个体间变异(P=0.001).结论 CYP2C19*2是影响中国汉族老年急性冠脉综合征患者氯吡格雷抗血小板反应性的主要药物基因组学相关因素.     

急性冠状动脉综合征患者氯吡格雷反应性的影响因素探讨

目的 探讨影响氯吡格雷治疗急性冠状动脉综合征(ACS)反应性的因素.方法 采用传统的光学血小板聚集仪对2005年9月至2006年4月在首都医科大学附属北京同仁医院住院治疗的72例ACS患者分别在服用氯吡格雷前和服药后7 d测定10 μmol/L二磷酸腺苷诱导的血小板聚集率.根据血小板聚集抑制率(△A),将入选人群划分为低反应组和正常反应组.采用Logistic回归分析对可能影响到氯吡格雷反应性的因素进行统计分析.结果 两组的基线特征显示与正常反应组相比,低反应组的体重指数、肥胖人群和ST段抬高心肌梗死的比例较低,高血压和糖尿病的比例较高(P均＜0.05).独立样本t检验的进一步分析证实除了肥胖,高血压、糖尿病以及ACS的种类对氯吡格雷反应性均存在影响(P＜0.05).Logistic多元回归分析发现高血压和服药前血小板聚集率(Apre)是影响氯吡格雷反应性的主要因素(OR分别为15.757和1.131,P＜0.01).结论 高血压和Apre是影响氯吡格雷反应性的主要因素.     

Safety and efficacy of clopidogrel reloading in patients on chronic clopidogrel therapy who present with an acute coronary syndrome and undergo percutaneous coronary intervention

The clinical safety and efficacy of clopidogrel reloading in patients receiving long-term clopidogrel therapy who present with acute coronary syndromes and undergo percutaneous coronary intervention have not yet been evaluated. The study cohort comprised 1,368 consecutive patients receiving long-term clopidogrel therapy (75 mg/day) who had presented with acute coronary syndromes and underwent coronary artery stent implantation. In total, 926 patients were given a 600-mg clopidogrel loading dose (reload cohort) before cardiac catheterization, while 442 patients were not reloaded (no-reload cohort). Patients who had presented with cardiogenic shock or stable angina were excluded. The 2 cohorts were well matched for the conventional risk factors for coronary artery disease. The analyzed clinical end points of death (1.1% vs 0.9%, p = 0.77), death or Q-wave myocardial infarction (0.9% vs 0.9%, p = 1.0), target lesion revascularization (0.2% vs 0.8%, p = 0.45), target vessel revascularization (1.1% vs 1.1%, p = 1.0), and major adverse cardiac events (2.0% vs 1.8%, p = 0.8) were similar between the no-reload and reload groups at 30 days. The in-hospital rates of major bleeding and gastrointestinal bleeding were also similar between the 2 cohorts. There were no cases of definite stent thrombosis. In conclusion, patients receiving long-term clopidogrel therapy who present with acute coronary syndromes do not gain any clinical benefit from additional reloading with clopidogrel.     

国产氯吡格雷对急性冠脉综合征经皮冠脉介入术的疗效

目的：研究国产氯吡格雷用于非ST段抬高急性冠脉综合征（NSTEACS）急诊经皮冠脉介入（PCI）治疗患者的疗效及安全性。方法：确诊NSTEACS并接受急诊PCI的患者176例,分成国产氯吡格雷组（接受泰嘉治疗,89例）和进口氯吡咯雷组（接受波立维治疗,87例）。PCI治疗前两组分别接受泰嘉、波立维每日600mg。PCI后每日分别接受75mg至1年以上。观察两组患者的疗效及不良反应的发生情况。结果：国产氯吡格雷组与进口氯吡格雷组达到的完全血运重建率（79．8％比89．3％．P=0．477）,主要不良心脑血管事件（MACCE）发生率（9．0％比6．9％,P=0．608）,不良反应的发生率（5．6％比8．0％,P=0．523）均无显著差异。结论：国产氯吡格雷（泰嘉）治疗急性非ST段抬高心肌梗死的疗效和安全性与进口氯吡格雷相当。     

Antiplatelet efficacy of long-term treatment with clopidogrel besylate in patients with a history of acute coronary syndrome: comparison with clopidogrel hydrogen sulfate

The efficacy of clopidogrel therapy in patients with an acute coronary syndrome (ACS) has been established using the clopidogrel hydrogen sulfate (CHS) formulation. We compared the antiplatelet effectiveness of long-term administration of the original CHS with a generic clopidogrel besylate (CB) salt formulation in 86 patients with a history of an ACS. At 1 month after the episode, patients receiving 75 mg/d CHS were randomized to continue with CHS (n = 41) or to switch to 75 mg/d CB (n = 45). Platelet aggregation, vasodilator-stimulated phosphoprotein (VASP) phosphorylation, P-selectin expression, and platelet-leucocyte conjugates were determined before randomization and at 6 months afterward. No difference in any platelet parameter studied was observed between the 2 groups either before randomization or after 6 months of treatment with CHS or CB. We conclude that there is no difference in the antiplatelet efficacy between CB and CHS during long-term administration in patients with a history of an ACS.     

氯吡格雷对急性冠脉综合征患者炎性标记物的影响

目的:探讨氯吡格雷对急性冠脉综合征(ACS)患者炎性标记物的影响。方法:入选在我院住院治疗的ACS患者158例,其中不稳定型心绞痛患者67例、非ST段抬高型心肌梗死患者42例、ST段抬高型心肌梗死49例。根据临床用药方式的不同所有患者被分为联合治疗组(80例,氯吡格雷+阿司匹林)和阿司匹林治疗组(78例,阿司匹林),检测两组患者治疗前,治疗后第7、14d血清高敏C-反应蛋白(hsCRP)、P-选择素(P-selec-tin)、白细胞介素-6(IL-6)水平。结果:治疗第7d,两组患者hsCRP、IL-6以及P-选择素均较治疗前显著升高(P<0.05);阿司匹林治疗组上升幅度显著高于联合治疗组(P<0.05);治疗第14d,两组患者上述指标均较治疗前显著降低(P<0.01),与阿司匹林组比较,联合治疗组hsCRP[(3.48±1.98)mg/L比(2.93±1.16)mg/L]、IL-6[(9.81±4.58)μg/L比(8.98±3.52)μg/L]、P-选择素[(9.56±4.67)ng/ml比(9.11±4.57)ng/ml]水平降低更显著(P均<0.05)。两组患者出血情况差异无显著性(P>0.05)。结论:氯吡格雷能显著降低急性冠脉综合征患者炎性标志物水平,这可能是其发挥作用的机制之一。     

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.     

Long-term cost-effectiveness of clopidogrel given for up to one year in patients with acute coronary syndromes without ST-segment elevation

OBJECTIVES: We sought to evaluate the long-term cost-effectiveness of clopidogrel for up to one year after an acute coronary syndrome (ACS) without ST-segment elevation. BACKGROUND: The efficacy of platelet inhibition with clopidogrel for up to one year after ACS was demonstrated in the Clopidogrel in Unstable angina to prevent Recurrent Events (CURE) trial, a randomized trial of 12,562 patients in 28 countries that was conducted between 1998 and 2000. Patients were given clopidogrel (300-mg load followed by 75 mg/day) versus placebo, both in addition to aspirin, for a mean of nine months. METHODS: We used patient-level clinical outcomes and resource use from the CURE trial and estimates of life expectancy gains as a result of the prevention of the clinical events of death, stroke, and myocardial infarction on the basis of data from external sources. RESULTS: Excluding clopidogrel costs, average costs of hospitalizations alone were 325 dollars less for the clopidogrel arm (95% confidence interval -722 dollars to 45 dollars) using diagnosis-related group-based Medicare reimbursement rates. When including clopidogrel costs (766 dollars greater for the clopidogrel arm), average total costs were 442 dollars higher for the clopidogrel arm (95% confidence interval 62 dollars to 820 dollars). The incremental cost-effectiveness ratio (ICER) on the basis of the Framingham Heart Study was 6,318 dollars per life-year gained (LYG) with clopidogrel, with 94% of bootstrap-derived ICER estimates <50,000 dollars/LYG; based on Saskatchewan, the ICER was 6,475 dollars/LYG with 98% of estimates <50,000 dollars. CONCLUSIONS: Platelet inhibition with clopidogrel in patients for up to one year after presentation with an acute coronary syndrome is both effective and cost-effective.     

急性冠状动脉综合征非介入治疗中的抗血小板治疗

急性冠状动脉综合征(ACS)的特征是冠状动脉斑块破裂、血小板活化和血栓形成.因此抗血小板药物在ACS治疗中有着重要的地位.本文综述了抗血小板治疗在ACS非介入治疗中的研究现状和进展.     

Tailored antiplatelet therapy to improve prognosis in patients exhibiting clopidogrel low-response prior to percutaneous coronary intervention for stable angina or non-ST elevation acute coronary syndrome

Aim: To investigate whether an intensified antiplatelet regimen could improve prognosis in stable or non-ST elevation in acute coronary syndrome (ACS) patients exhibiting high on-treatment platelet reactivity (HTPR) on clopidogrel and treated with percutaneous coronary intervention (PCI). There is a wide variability in the platelet reactivity to clopidogrel and HTPR has been associated with a poor prognosis. Methods: In this observational study, 923 consecutive patients without ST-elevation myocardial infarction (STEMI) and adequately pre-treated with clopidogrel were screened for HTPR with multiple electrode aggregometry after assessment of the coronary anatomy. Patients were grouped based on their response to clopidogrel and the assigned antiplatelet strategy. The primary endpoint was a composite of cardiovascular death, myocardial infarction, stroke, or stent thrombosis. Results: HTPR was demonstrated in 237 patients (25.7%). Of these, 114 continued on conventional clopidogrel therapy, while the remaining 123 received intensified antiplatelet therapy with either double-dose clopidogrel (150?mg daily, n?=?55) or the newer P₂Y₁₂-inhibitors, prasugrel or ticagrelor (n?=?68) for at least 30 days after the index procedure. The median follow-up was 571 days (interquartile range, 373–746). Intensifying antiplatelet therapy reduced the rate of the composite endpoint (p?<?0.001). After adjustment for potential confounders, HTPR in combination with conventional clopidogrel therapy remained independently associated with an increased risk of cardiovascular events (hazard ratio (HR), 2.92; 95% CI, 1.90–4.48), whereas intensified treatment reduced the risk to a level equivalent to that of patients exhibiting normal platelet reactivity (HR, 1.08; 95% CI, 0.59–1.99). Conclusion: Tailored antiplatelet therapy significantly reduced the event rate in patients exhibiting HTPR prior to PCI.     

替格瑞洛和氯吡格雷治疗ACS择期PCI术后患者效果分析

目的 分析替格瑞洛和氯吡格雷对急性冠脉综合征（ACS）患者择期经皮冠状动脉介入（PCI）治疗的有效性及安全性。方法 诊断为ACS并择期行PCI术的患者1 159例随访1年,依患者服用双重抗血小板药物不同分为替格瑞洛组(n=312)和氯吡格雷组(n=847),其中3例在随访过程中排除,27例失访,最终纳入1 129例,替格瑞洛组(n=303)和氯吡格雷组(n=826)。比较两组患者基线资料的差异及主要心血管不良事件（MACE,包含心血管死亡、心肌梗死、缺血性卒中）和大出血事件（美国出血学术研究会制定的出血分级标准中Ⅱ型、Ⅲ型及Ⅴ型出血）的发生率。结果 替格瑞洛组患者肌钙蛋白I（TnI）偏高,左室射血分数（LVEF）值偏低,植入支架数多,最大狭窄率高,复杂病变比例高,桡动脉入路少,分次PCI比例高（均P<0.05）。替格瑞洛组发生MACE事件（15.2%）与氯吡格雷组（12.6%）相比〔危险比(hazard ratio,HR)=1.226,95%可信区间0.867~1.735,P=0.249〕及大出血事件替格瑞洛组（0.7%）与氯吡格雷组（0.7%）相比（HR=1.093,95%可信区间0.212~5.634,P=1）,差异均无统计学意义。单因素分析影响预后的因素包括:男性、城市来源、LVEF、分次PCI是保护性因素;高脂血症、脑梗病史、病变血管数目、安放支架数目、最大狭窄率、醛固酮受体拮抗剂是危险性因素,利用可能影响患者预后的因素作为因子多元逐步Cox比例风险回归模型模型分析结果是替格瑞洛与氯吡格雷HR=1.118,95%可信区间0.755~1.656,P>0.05。结论 替格瑞洛和氯吡格雷用于ACS择期PCI术后患者的疗效和安全性相当。     

De-escalation from ticagrelor to clopidogrel in acute coronary syndrome patients: a systematic review and meta-analysis

Journal of Thrombosis and Thrombolysis - Stress-induced cardiomyopathy (SCM), is a reversible cardiomyopathy characterized by transient systolic dysfunction following an acute physiologic stress....     

急性冠状动脉综合征高龄患者介入治疗后双联抗血小板长期治疗的安全性研究

目的:观察急性冠状动脉综合征(ACS)高龄患者经皮冠状动脉介入治疗(PCI)后长期联合应用阿司匹林和氯吡格雷的安全性。方法:将接受PCI的416例ACS患者分为非高龄组(A组,年龄0.05)。2组出血发生率分别为3.2%和4.0%(P>0.05),血小板及白细胞减少发生率组间差异无统计学意义(P>0.05)。多元Logistic回归分析结果提示阿司匹林长期维持治疗、氯吡格雷维持治疗时间超过12个月、合并使用质子泵抑制剂是ACS患者PCI后长期使用双联抗血小板药并发出血的独立危险因素[比值比(OR)分别为0.048、5.396、0.181,均P0.05)。结论:75岁以上的高龄ACS患者PCI后长期双联抗血小板治疗的出血发生率与75岁以下人群相比并未明显增加,但长期双联抗血小板治疗仍需注意防止出血并发症的发生。     

A cost analysis in patients with acute coronary syndrome using clopidogrel in addition to aspirin in a Hong Kong public hospital

Results from the Clopidogrel in Unstable Angina to Prevent Recurrent Events (CURE) study showed that clopidogrel plus aspirin, compared to aspirin alone, reduced cardiovascular events (death, myocardial infarction, and stroke) in patients with acute coronary syndromes (ACS). Yet the acquisition cost of clopidogrel is much higher. It would therefore be worthwhile to compare the long-term cost impact of these 2 regimens. Until recently, only very few patients with ACS received clopidogrel-aspirin combination therapy in Hong Kong. Therefore, a hypothetical cohort was formed and compared to a real group of patients treated with aspirin alone. For the aspirin group, medical history was reviewed and cardiovascular and gastrointestinal events occurring in a period of 12 months after initiation of therapy were recorded. The target cost items included hospitalisation, emergency room visits, outpatient clinic visits, related medications, diagnostic tests, procedures, and surgery. For the hypothetical cohort, the probabilities/relative risks for clinical events were adopted from the CURE study. Fifty-four consecutive patients with ACS receiving aspirin therapy were identified and studied between January 1, 2001 and December 31, 2001 from a major public hospital in Hong Kong. The average cost of management per patient over the 12 month period for the aspirin group was HK$85,324 (US$10,940, HK$7.8 = 1 US$) versus the hypothetical cohort HK$83,903 (US$10,757). Hospitalisation represented the major cost item (64.6%), followed by the cost of investigational tests (14.5%) and procedural cost (11.6%). According to our analytical model, the overall cost impact between clopidogrel plus aspirin versus aspirin alone in the 2 groups of patients was similar.