国产氯吡格雷在急性心肌梗死急诊冠状动脉介入治疗中的临床观察

目的：观察国产氯吡格雷（泰嘉）和进口氯吡格雷（波立维）在急诊PCI治疗AMI中的临床疗效及并发症情况。方法：选择2005-01/2008-12我院行急诊PCI治疗AMI的260例患者,随机分为进口氯吡格雷（波立维）组和国产氯吡格雷（泰嘉）组,各130例,术前均给予负荷量300 mg口服,其他药物：阿司匹林、β-受体阻滞剂、ACEI和低分子肝素等应用相同。观察30 d内两组病例皮下出血、消化道出血、颅内出血、过敏反应、白细胞减少及血小板减少情况。结果：两组病例全部手术成功,术后30 d内均无严重的消化道出血、颅内出血及急性、亚急性冠脉事件发生。皮下出血、过敏反应、白细胞、血小板减少两组病例发生率相似,无统计学意义。结论：国产氯吡格雷（泰嘉）和进口氯吡格雷（波立维）一样具有明确的抗血小板、抑制血栓形成作用,能预防PCI术后再发急性、亚急性血栓形成,在急诊PCI术后应用同样安全、有效,但PCI术后患者常常需要长期服药,国产氯吡格雷价格低,更具有依从性,值得推广应用。     

等剂量国产与进口氯吡格雷对急诊PCI术后影响的等效性比较

目的 探讨等剂量国产氯吡格雷(泰嘉)和进口氯吡格雷(波立维)对急性心肌梗死(AMI)患者急诊经皮冠状动脉内介入治疗(PCI)术后疗效及安全性是否相同.方法 前瞻性入选204例接受急诊PCI治疗的AMI患者,分为泰嘉组(123例)及波立维组(81例),在急诊室给予300 mg负荷剂量,序贯75 mg/d,随访3～28个月,观察急性、亚急性、晚期、极晚期支架内血栓和心肌梗死、心源性死亡、脑卒中的联合终点不良心脏事件(MACE)的影响以及出血等相关副作用的影响.结果.泰嘉组和波立维组均无支架内血栓和出血事件;波立维组有2例心源性死亡,分别为心源性休克及心脏破裂;两组靶血管重建及联合终点事件发生率,经统计学检验,差异无统计学意义(χ2分别为0.000和0.921,P值分别为0.989和0.337);两组之间累积MACE经Kaplan-Meier生存分析计算,绘制K-M曲线,经Log Rank比较,差异无统计学意义(χ2=0.679,P=0.410).结论.等剂量国产与进口氯吡格雷对AMI患者急诊直接PCI术后疗效及安全性相似.     

高龄冠心病患者PCI术后国产氯吡格雷抗栓治疗效果观察

【目的】观察国产氯吡格雷（泰嘉）对高龄冠心病患者（〉75岁）经皮冠状动脉介入治疗（PCI）近期预后的影响。【方法】接受冠状动脉支架植入术的65例高龄冠心病患者分为泰嘉组（n=39）和进口氯吡格雷（波立维）组（n=26）。评价PCI术后6个月的主要心血管不良事件（MACE）发生率及再狭窄率,并观察术前、术后的粒细胞、血小板数量以及各种出血并发症。【结果】6个月随访期内,两组患者的MACE发生率及再狭窄率无显著差异;出血并发症以及粒细胞、血小板数量无显著差异。【结论】国产氯吡格雷应用于高龄PCI术后抗栓安全有效。     

氯吡格雷双倍剂量对冠脉介入术后氯吡格雷抵抗患者缺血及出血事件的影响

目的 评价经皮冠状动脉介入治疗(PCI)后,氯吡格雷抵抗患者服用双倍剂量氯吡格雷的有效性及安全性.方法 依据血栓弹力图(TEG)的测定结果,将入选的134例氯吡格雷抵抗患者分为常规剂量组67例与双倍剂量组67例,随访观察两组患者PCI术后6个月时临床缺血及出血事件的发生率.结果 双倍剂量组与常规剂量组患者相比较,主要不良心血管事件的发生率明显降低,而出血事件发生率在两组患者间比较,差异无统计学意义.结论 增加氯吡格雷的维持剂量,可以减少冠心病患者PCI术后缺血事件的发生,且不增加患者的出血风险.     

国产氯吡格雷在冠心病合并糖尿病患者冠状动脉支架术后的临床应用

目的评价国产氯吡格雷在冠心病合并糖尿病患者冠脉支架术后临床应用的疗效和安全性。方法连续选取冠心病合并糖尿病并成功接受冠状动脉支架术的患者168例,其中术后接受国产氯吡格雷(泰嘉)的患者73例(泰嘉组),接受进口氯吡格雷(波立维)的患者95例(波立维组)。术后进行6个月临床随访,观察两组患者主要不良心血管事件和出血事件的发生率。结果术后两组患者主要不良心血管事件的发生率分别为15.1%和12.6%,出血事件的发生率分别为4.1%和6.3%,差异均无统计学意义。结论国产与进口氯吡格雷在冠心病合并糖尿病患者冠脉支架术后的疗效和安全性方面作用相似。     

老年冠心病患者经皮冠状动脉介入术后联合应用阿司匹林和氯比格雷的安全性研究

目的评价老年患者择期经皮冠状动脉介入治疗(PCI)术后联合应用氯比格雷和阿司匹林的安全性。方法随访因冠心病行择期PCI术的老年男性患者132例,所有患者PCI术后连续服用氯比格雷75 mg/d和阿司匹林100 mg/d,共12个月。观察患者服药期间主要心血管事件(急性或亚急性血栓形成、心绞痛、再发心肌梗死、心力衰竭、死亡等)及出血(严重出血、轻微出血)的发生率。应用16排螺旋CT复查冠状动脉造影。结果全部132例患者无心血管事件发生;仅3例出现消化道出血;冠脉CT检查未发现支架内再狭窄。结论老年患者PCI术后联合应用氯比格雷及阿司匹林可减少PCI术后心血管事件的发生,且副作用少。     

PCI术后应用氯吡格雷药物脱敏治疗的护理

冠心病是目前我国成人心脏病住院和死亡的首要原因[1],经皮冠状动脉介入治疗(percutaneous coronary interventions,PCI)是治疗冠心病的有效方法.根据国际上各大临床试验的结果,仅服用一定剂量的阿斯匹林和氯吡格雷就可以很好地预防支架内血栓形成和冠心病介入术后血栓事件的发生[2].<抗栓指南>建议[3]:行冠状动脉介入治疗的病人中稳定性心绞痛病人置入金属裸支架后应用阿斯匹林和氯吡格雷双联抗血小板药物3周～4周,置入药物洗脱支架应服用双联抗血小板药物6个月～12个月.     

经皮冠状动脉介入治疗术双抗治疗1年后患者单用阿司匹林或氯吡格雷远期预后对比分析

目的:比较经皮冠状动脉介入治疗(PCI)术双抗治疗1年后患者服用阿司匹林或氯吡格雷远期预后差异,并分析原因。方法:回顾性分析2017年8月至12月植入药物涂层支架后采用双抗血小板治疗1年的168例患者的临床资料。依据患者抗血小板治疗1年后服药情况,将其分为阿司匹林组(100 mg/d,85例)和氯吡格雷组(75 mg/d,83例)。继续观察18个月,比较两组患者主要不良心血管事件(MACEs)以及服药期间出血情况。结果:两组患者心血管相关死亡、再发心绞痛、支架内再狭窄等观察终点事件差异无统计学意义,且均未发生严重出血事件。阿司匹林组轻中度出血比例明显高于氯吡格雷组(16.5%vs 4.8%,P=0.015),主要为胃出血事件增多(8.2%vs 1.2%,P=0.032)。Kaplan-Meier生存曲线结果表明,随访期间两组MACEs发生率差异无统计学意义(log rank=0.014,P=0.905),但氯吡格雷组轻中度出血事件明显少于阿司匹林组(log rank=5.986,P=0.014)。发生出血事件的患者中女性比例(61.1%vs 34.0%,P=0.024)以及年龄[(71.89±8.37)岁vs(64.75±9.02)岁,P=0.002)]高于未出血患者。多因素logistic回归分析发现,年龄[Exp(B)=4.771, 95%CI 1.313～17.344,P=0.018]、性别[Exp(B)=0.361, 95%CI 0.129～1.009,P=0.049]为出血事件的独立危险因素。结论:PCI术双抗治疗1年后患者单用氯吡格雷或阿司匹林远期获益相似,但单用氯吡格雷后轻中度出血风险降低;PCI术双抗治疗1年后的高龄女性患者可考虑长期服用氯吡格雷片75 mg/d治疗。     

国产雷帕霉素洗脱支架远期预后的临床研究

目的观察冠心病患者应用国产雷帕霉素洗脱支架后临床不良心血管事件(major adverse cardia cevent,MACE)包括心源性死亡、再发非致死性心肌梗死、再次血运重建的发生率。方法2003年11月至2006年12月,共入选267例患者,国产雷帕霉素(Firebird,上海微创公司)支架组145例,进口雷帕霉素(Cypher,美国强生公司)支架组122例。术后严格要求患者服用阿司匹林和噻氯匹定或氯吡格雷至少12个月。通过门诊或电话随访术后患者MACE的发生率,部分患者进行了冠状动脉造影复查。结果随访(31±11)个月,失访患者9例(Firebird组6例、Cypher组3例),失访率3.37%。随访期间总的MACE的发生率在Firebird组10.79%、Cypher组11.76%,两组无显著性差异(P=0.95),两组冠状动脉介入治疗(PCI)术后<1年及>1年MACE分别为5.04%、7.02%和5.04%、8.08%,P<0.05;Firebird支架和Cypher支架的血栓发生率分别为1.44%、1.68%,P>0.05。两组冠状动脉造影再狭窄率分别为17.6%(6/34)、19%(8/42),无显著性差异。结论远期临床随访结果表明,国产Firebird支架与Cypher支架临床心血管事件、支架内血栓的发生率均较低,两组无显著性差异,两者的安全性与有效性相似。延长联合抗血小板治疗时间很有必要。     

替格瑞洛与氯吡格雷在行冠状动脉介入治疗的不稳定型心绞痛患者中血小板功能抑制及临床疗效和安全性的研究

目的探讨对于不稳定型心绞痛(UAP)行PCI治疗的患者,术前服用氯吡格雷负荷剂量300 mg,短时间内(PCI术后1 d)血小板聚集功能抑制相对低下的患者更换替格瑞洛后能否取得更好的血小板聚集功能的抑制、较好的临床疗效及安全性如何。方法入选40例UAP常规行PCI术治疗患者[此40例患者均为术前服用氯吡格雷负荷量300 mg,术后予以常规氯吡格雷75 mg qd,于PCI术后1 d采用血栓弹力图(TEG)检测ADP途径诱导血小板聚集功能的抑制率(IPA)<50%,即对氯吡格雷反应相对低下的患者],将40例氯吡格雷反应相对低下的患者随机分为2组,A组继续用氯吡格雷75 mg qd,B组替换为替格瑞洛90 mg Bid,分别于服药后1周,1个月时采用TEG的方法复测IPA,并观察术后1个月的主要缺血事件(死亡、心肌梗死、靶血管血运重建、反复心绞痛发作)及出血事件。结果两组服用负荷剂量氯吡格雷300 mg PCI术后第1天ADP诱导的IPA(基线PDA)差异无统计学意义,1周后复测ADP诱导的IPA,B组明显高于A组[(81.84±11.10)%vs.(69.74±11.84)%,P=0.030];1个月后复测ADP诱导的IPA,B组仍明显高于A组[(85.91±5.98)%vs.(76.19±9.51)%,P=0.014],差异均有统计学意义。1个月临床随访结果两组均无死亡、心肌梗死、靶血管血运重建、反复心绞痛发作及脑卒中患者,在安全性上两组均无严重的出血及颅内出血。结论本研究提示替格瑞洛较氯吡格雷能快速地产生更强效的血小板抑制作用,在安全性上较氯吡格雷并没有增加主要出血事件的发生率,提示了其在介入治疗中应用的安全性。     

Aspirin and clopidogrel resistance

Despite aspirin's and clopidogrel's proven benefit in reducing cardiovascular (CV) events, recurrent CV events still occur in patients receiving antiplatelet therapy. Many of these patients are resistant or only partially responsive to the antiplatelet effects of aspirin and clopidogrel, as determined by standard platelet assays. However, current clinical guidelines do not support routine screening for aspirin or clopidogrel resistance, in part because determination of the most appropriate screening test has not been established. This review attempts to (1) describe the phenomena of clinical aspirin and clopidogrel resistance (ie, treatment failure), (2) discuss the complexity of defining and identifying aspirin and clopidogrel resistance, (3) identify factors that may be responsible for aspirin and clopidogrel resistance, (4) outline several standard platelet function assays and their limitations, and (5) describe potential new antiplatelet therapies that may benefit aspirin- or clopidogrel-resistant patients.     

Antiplatelet effect of clopidogrel]

Clopidogrel is a new thieno-pyridine derivative and has a more potent inhibitory effect on platelet aggregation, dependent on ADP rather than ticlopidine. In a phase I study performed in Japan, significant inhibition of ADP-induced platelet aggregation and prolongation of bleeding time was observed in the dose range of 25, 50 and 75 mg. These effects were comparable to 200 or 300 mg of ticlopidine. Antithrombotic effects have also been shown in experimental animal models. Clopidogrel is expected to reduce the incidence of neutropenia since smaller doses are sufficient to suppress platelet aggregation compared to ticlopidine. Clopidogrel has been proven to be a potent and well-tolerated antiplatelet agent for atherosclerosis patients at risk of thrombosis, in Europe.     

Comparing the antiplatelet effect of clopidogrel hydrogensulfate and clopidogrel besylate: a crossover study

Background  

Clopidogrel hydrogensulfate is a thienopyridine acting as an important antiplatelet agent alone or in combination with acetyl salicylic acid to prevent cardiovascular complications. A different clopidogrel salt, clopidogrel besylate, was approved in Germany as a “new drug” in May 2008. Only one study with 46 healthy men compared the plasma concentrations of both clopidogrel formulas. In our crossover study we measured the antiplatelet effect of clopidogrel hydrogensulfate (CHS, clopidogrel bisulfate) and clopidogrel besylate (CB) using two techniques, whole blood impedance aggregometry and flow cytometry in healthy subjects.     

Hematologic adverse effects of clopidogrel

Clopidogrel is used as a frontline antiplatelet agent in patients with coronary artery disease, cerebrovascular disease, and peripheral vascular disease. Hematologic complications and bleeding have been the most feared outcome of antithrombotic and antiplatelet agents. Among the thienopyridines, clopidogrel is considered to be a safer alternative to ticlopidine due to its decreased incidence of hematologic adverse effects. Although thrombotic thrombocytopenia purpura is the most reported hematologic adverse effect of clopidogrel; neutropenia, acquired hemophilia, isolated thrombocytopenia or idiopathic immune thrombocytopenia, and thrombotic thrombocytopenia purpura with hemolytic uremic syndrome are other rare yet recognized hematologic adverse effects of clopidogrel. Patients treated with clopidogrel should be carefully monitored for hematologic adverse effects especially in the first 2 to 3 months after initiation of therapy. Early recognition and prompt initiation of treatment can be life saving in patients who have hematologic adverse effects to clopidogrel. We have drafted this review by performing literature search using Medline, Pubmed, and EMBASE search engine with relevant search words for all reported hematologic adverse effects and manifestations of clopidogrel and their management.     

Associations of PER3 polymorphisms with clopidogrel resistance among Chinese Han people treated with clopidogrel

BackgroundChanges in circadian rhythm are related to various diseases, such as immune system diseases and cardiovascular diseases. The PERIOD3 (PER3) clock gene is one of the most important genes in the rhythm regulation system. Our goal was to evaluate the possible association between the PER3 rs228729 (T/C) polymorphism or PER3 rs2797685(T/C) polymorphism and clopidogrel resistance (CR) and to study the impact of clinical baseline data on clopidogrel resistance.Methods PER3 polymorphisms rs2797685 (T/C) and rs228729 (T/C) were assessed in 156 patients with (72) and without (84) CR. Blood samples were collected and analyzed after the application of clopidogrel for interventional therapy.ResultsAge, albumin, PLT, and PCT levels influenced the risk of CR (p < 0.05). For rs2797685, when the PCT value was greater than 0.19, patients with the TT + TC genotype had an increased risk of clopidogrel resistance compared with those with the CC genotype (PCT ≥ 0.19, p = 0.014; PCT p = 0.004). In patients with albumin values greater than 40 or PCT greater than 0.19, those with the rs228729 TT + TC genotype had an increased risk of clopidogrel resistance compared with those with the CC genotype (albumin≥40, TT+TC:CC, p = 0.01, albumin p = 0.005; PCT ≥ 0.19, TT+TC:CC, p < 0.001, PCT p = 0.004). Logistic regression analysis of clinical baseline data and genotype showed that high albumin is a protective factor against clopidogrel resistance. The PER3 gene polymorphism has no clear correlation with clopidogrel resistance.ConclusionIn summary, our research shows that PER3 SNPs may be helpful to assess the pathogenesis of CR.     

Fatal liver injury associated with clopidogrel

Clopidogrel, an adenosine diphosphate receptor blocker, is widely used as an adjunctive antiplatelet therapy in acute coronary syndrome and percutaneous coronary stenting. It appears to be a safe drug with few occurrences of liver side‐effects that usually resolved after drug withdrawal. We report a serious liver injury with fatal outcome in a 63‐year‐old man developed 19 days after starting clopidogrel for percutaneous coronary stenting.     

Stent thrombosis in a clopidogrel nonresponder

Stent thrombosis is a known complication of percutaneous coronary intervention (PCI) following coronary stent deployment. Dual antiplatelet therapy is standard of care following PCI, however, recent studies demonstrate marked variability in platelet response to clopidogrel. This case study explores the management of a clopidogrel nonresponder who presented with recurrent stent thrombosis despite traditional pharmacologic management.     

Impact of P-glycoprotein on clopidogrel absorption

OBJECTIVE: The antiplatelet activity of clopidogrel is characterized by considerable interindividual differences. Variable intestinal absorption is suggested to contribute to the inconsistencies in response. We tested the hypothesis that the intestinal efflux transporter P-glycoprotein (P-gp) limits the oral bioavailability of clopidogrel and that variance in the MDR1 gene encoding P-gp predicts absorption variability. METHODS AND RESULTS: P-gp-mediated transport of clopidogrel was assessed by transflux, influx, and efflux experiments by use of Caco-2 cells. Inhibition of P-gp activity by different modulators increased the absorptive clopidogrel flux across Caco-2 monolayers from 0.51+/-0.19 pmol/cm2 (mean+/-SD) at baseline by a maximum of 5- to 9-fold (P<.001) and the intracellular accumulation from 0.99+/-0.11 pmol/mg protein by a maximum of 2.5-fold (P<.001) in response to 1-micromol/L clopidogrel and decreased clopidogrel efflux to the level of passive diffusion. In 60 patients with coronary artery disease who underwent percutaneous coronary intervention, the peak plasma concentration (Cmax) and the total area under the plasma concentration-time curve (AUC) of clopidogrel and its active metabolite after a single oral loading dose of 300, 600, or 900 mg were tested for correlation with the MDR1 genotype. In the 300-mg and 600-mg groups (but not in the 900-mg group) Cmax and AUC values were lower in subjects homozygous for the MDR1 3435T variant compared with subjects with the 3435C/T and 3435C/C genotypes. After the 600-mg loading dose, Cmax values (mean+/-SD) of clopidogrel and its active metabolite in 3435T/T carriers were 13.3+/-5.2 ng/mL and 2.5+/-1.2 ng/mL, respectively, compared with 49.7+/-41.6 ng/mL (P=.001) and 6.6+/-3.6 ng/mL (P=.011), respectively, in 3435C/T and 3435C/C carriers; AUC values were 1502+/-463 ng/mLxmin for clopidogrel and 209+/-99 ng/mL x min for its active metabolite in 3435T/T carriers compared with 7057+/-5443 ng/mLxmin (P=.0006) and 744+/-541 ng/mLxmin (P=.011), respectively, in 3435C/T and 3435C/C carriers. CONCLUSIONS: Clopidogrel absorption and thereby active metabolite formation are diminished by P-gp-mediated efflux and are influenced by the MDR1 C3435T genotype.