两种他汀类药物对不同细胞色素P450酶2C19基因型患者氯吡格雷抗血小板作用的影响

目的观察2种他汀类药物对不同细胞色素P450酶(CYP)2C19基因型的急性冠状动脉综合征(ACS)患者氯吡格雷抗血小板作用的影响。方法选取接受CYP2C19基因型检测的老年ACS患者200例,根据服用他汀类药物及CYP2C19基因型分为6组:阿托伐他汀+快代谢组(A组)40例,瑞舒伐他汀+快代谢组(B组)40例;阿托伐他汀+中代谢组(C组)46例,瑞舒伐他汀+中代谢组(D组)46例;阿托伐他汀+慢代谢组(E组)14例,瑞舒伐他汀+慢代谢组(F组)14例。在使用氯吡格雷前(基线)、联合服用他汀类药物前(治疗前)及服用他汀类药物7 d(治疗后),测定二磷酸腺苷诱导的血小板聚集率;随访6个月,观察主要不良心血管事件(MACE)的发生率。结果与基线比较,治疗前和治疗后A组、B组、C组、D组、E组和F组血小板聚集率明显降低(P<0.05),且治疗后较治疗前更低[(3.9±0.2)%vs(5.2±0.3)%;(3.8±0.2)%vs(5.3±0.3)%;(4.9±0.4)%vs(5.3±0.3)%;(5.0±0.3)%vs(5.1±0.4)%;(5.0±0.4)%vs(5.2±0.3)%;(4.9±0.5)%vs(5.1±0.4)%,P<0.05];治疗后在相同基因代谢类型中,A组与B组、C组与D组、E组与F组血小板聚集率比较,无统计学差异(P>0.05);治疗后在不同基因代谢类型中,A组血小板聚集率明显低于C组和E组(P<0.05),B组血小板聚集率明显低于D组和F组,差异有统计学意义(P<0.05);C组与E组,D组与F组血小板聚集率比较,差异无统计学意义(P>0.05)。6组MACE发生率比较,差异无统计学意义(P>0.05)。结论2种他汀类药物对于同一代谢基因型组氯吡格雷抗血小板活性没有影响,对于不同代谢基因型患者氯吡格雷抗血小板活性有影响,氯吡格雷抗血小板活性受到CYP2C19基因多态性的影响。     

氯吡格雷对阿司匹林抵抗的影响及其与他汀类药物的相互作用

目的比较氯吡格雷联用不同种类的他汀类药物时血小板聚集率的差别,揭示其对氯吡格雷的抗血小板作用是否存在影响,明确氯吡格雷对阿司匹林抵抗的影响。方法将70例急性冠脉综合征(ACS)病人分为两组,阿司匹林组30例,入院后3d内口服阿司匹林300mg/d,后改为100mg/d至两周;联合用药组40例,阿司匹林服用如前,同时加用氯吡格雷75mg/d。于两周时采静脉血,应用比浊法分别测定二磷酸腺苷(ADP)和花生四烯酸(AA)诱导的血小板聚集率。又将联合用药组随机分为细胞色素氧化酶(CYP)3A4代谢的他汀组(A组,服阿托伐他汀10mg~40mg或辛伐他汀40mg或洛伐他汀40mg)和非CYP3A4代谢的他汀组(B组,服氟伐他汀80mg或普伐他汀20mg)各20例,两周时采静脉血测定血小板聚集率如前(仅观察ADP诱导的血小板聚集率)。结果联合用药组与阿司匹林组相比,两种不同诱导剂诱导的血小板平均聚集率均明显下降(P<0.05或P<0.01),其中以ADP诱导的血小板平均聚集率下降更显著,联合用药组阿司匹林抵抗(AR)与阿司匹林半抵抗(ASR)总发生率较单用阿司匹林组明显为低(P<0.05);CYP3A4代谢的他汀与非CYP3A4代谢的他汀组相比较,在与氯吡格雷联用时,对氯吡格雷抗血小板作用影响无统计学意义(P>0.05)。结论联用氯吡格雷可明显减少阿司匹林抵抗,从而减少不良心血管事件的发生。     

阿托伐他汀或瑞舒伐他汀与氯吡格雷合用在非ST段抬高型急性冠状动脉综合征患者支架置入术后的近期疗效比较

目的比较阿托伐他汀或瑞舒伐他汀与氯吡格雷合用在非ST段抬高型急性冠状动脉综合征(NSTE-ACS)支架置入术后患者的近期疗效。方法共154例NSTE-ACS的患者接受支架置入术后,随机分为服用阿托伐他汀组(74例)及服用瑞舒伐他汀组(80例),术前服用阿司匹林(100mg)5 d、氯吡格雷(75 mg)5 d以上或术前12 h以上顿服氯吡格雷300 mg及阿司匹林片300 mg,于术前服抗血小板药前、手术当天、术后3、7 d及术后1、6个月抽取静脉血测定二磷酸腺苷(ADP)(浓度为10μmol/L)诱导的血小板聚集功能,观察住院期间及6个月的主要不良心脏事件(MACE)。结果两组患者的临床基线资料及服药情况差异无统计学意义,服用氯吡格雷(75 mg)5 d或顿服300 mg能达到明显的血小板聚集率抑制作用,血小板聚集率在阿托伐他汀组由基线的(57.2±10.3)%降至手术当日的(32.5±11.2)%,而瑞舒伐他汀组分别为(59.1±9.8)%和(30.4±10.1)%(均为P<0.01),而且这种抑制作用稳定持续至6个月之后。6个月时两组间总的MACE发生率差异无统计学意义(13.0%比15.0%,P>0.05),两组心原性死亡、非致死性心肌梗死、靶血管重建术、支架内血栓形成及出血事件差异均无统计学意义(均为P>0.05)。结论接受冠脉支架置入术的NSTE-ACS患者,服用阿托伐他汀或瑞舒伐他汀后,短期内未发现对氯吡格雷抗血小板作用产生显著影响,且两组间的近期疗效相近。     

氯吡格雷联合应用他汀类药物药效及副反应观察

目的观察氯吡格雷药效及副反应是否因为合用他汀药物而受到影响。方法124例临床诊断不稳定型心绞痛（UA）患者均给予氯吡格雷300 mg顿服,继75 mg/d,随机分为合用氟伐他汀80 mg/d组、合用阿托伐他汀10mg/d组和对照组,给药前及治疗2周后分别测定其血小板聚集率和血常规。结果患者血小板聚集率均明显降低,与治疗前比较,差异有显著性,3组血小板聚集率降低幅度无显著性差异,3组均未发现中性粒细胞及血小板计数减少患者。结论联合应用氟伐他汀或阿托伐他汀后,氯吡格雷药效及副反应未受影响。     

阿托伐他汀可以消弱氯吡格雷抗血小板聚集的能力

氯吡格雷 (Clopidogrel)是一种无活性的前体药物 ,需要在肝脏内转化成活性物质 ,并通过与血小板P2YacADP受体结合而发挥其抗血小板聚集的作用。而氯吡格雷在人体肝内活性转化的机制 ,目前仍不清楚。在用一种新型的床旁血小板聚集度计测定氯吡格雷对血小板的功能影响时 ,该文的作者发现当患者同时服用阿托伐他汀 (Atorvastatin)时 ,氯吡格雷的抗血小板聚集作用就会显著降低。由于阿托伐他汀通过肝内的CyP3 A4酶代谢 ,因此该文的作者推测 ,阿托伐他汀可能抑制氯吡格雷通过P45 0CyP3 A4酶进行活性转化这一过程 ,从而消弱氯吡格雷抗血小板…     

阿托伐他汀与氯吡格雷对ACS患者氯吡格雷羧酸衍生物血浓度与血小板聚集率的影响

目的:测定急性冠状动脉综合征(ACS)患者氯吡格雷羧酸衍生物血浓度和血小板聚集率,观察阿托伐他汀和氯吡格雷有无相互作用。方法:对照组为25例健康受试者,ACS组为66例ACS患者。均口服阿司匹林100mg/d、氯吡格雷75mg/d、阿托伐他汀20mg/d,5d后暂停阿托伐他汀,继续氯吡格雷和阿司匹林口服4d,分别于第5天、第9天采用液相色谱串联质谱法测量氯吡格雷羧酸衍生物血浓度,流式细胞仪测定血小板聚集率,比较两组差异。结果:对照组第5天和第9天氯吡格雷羧酸衍生物血浓度分别为(5.76±0.87)ng/dl和(5.67±0.88)ng/dl(P=0.351),血小板聚集率分别为(44.25±16.37)%与(47.61±16.67)%(P=0.083)。ACS组第5天和第9天氯吡格雷羧酸衍生物血浓度分别为(5.96±0.87)ng/dl和(5.86±0.97)ng/dl(P=0.115),血小板聚集率分别为(47.70±15.07)%与(47.02±15.45)%(P=0.622)。相关性分析显示,血氯吡格雷羧酸衍生物浓度和血小板聚集率呈正相关。结论:氯吡格雷羧酸衍生物血浓度和血小板聚集率相关性良好,氯吡格雷和阿托伐他汀未见相互作用。     

氯吡格雷和他汀联用对急性冠脉综合征患者临床观察

目的探讨急性冠脉综合征患者氯吡格雷和不同他汀联用在短期内对血小板聚集的影响,并观察对PCI术后心肌损伤以及临床事件的影响。方法60名ACS患者随机分为氯吡格雷和阿托伐他汀(10mgqd)组(30例)以及氯吡格雷和氟伐他汀(40mgqd)组(30例),分别测定联合用药前、用药后24小时、1周血小板聚集率,PCI术后24小时测定心肌损伤标志物,观察术后1周、半年临床心血管事件。结果两组联合用药24小时、1周血小板聚集率无统计学差异(P>0.05),PCI术后心肌损伤标志物未显著升高,两组导致不良心血管事件发生无统计学差异。结论ACS患者常规用量阿托伐他汀、氟伐他汀与氯吡格雷联合应用是安全、有效的,对氯吡格雷的抗血小板作用未见影响。     

阿托伐他汀联合氯吡格雷对急性冠脉综合征血小板聚集率的影响

目的:探讨急性冠脉综合征(ACS)患者急性期负荷剂量氯吡格雷联合阿托伐他汀或普伐他汀对血小板聚集率和主要不良心血管事件发生率的影响。方法:102例ACS患者被随机分成两组:普伐他汀组(P组)和阿托伐他汀组(A组),两组均予氯吡格雷300mg顿服后,75mg/d维持。P组予普伐他汀。入院后24h内和第14天分别测定TC、HDL-C、LDL-C、血小板聚集率(PAR)、肝功能,并统计两组主要不良心血管事件的发生率。结果:(1)两组TC、HDL-C、LDL-C水平在基础状态和第14d,差异无显著性(P>0.05);(2)P组或A组PAR在治疗后和基线相比,差异有显著性(P<0.05);但P、A两组在治疗后相比,差异无显著性(P>0.05);(3)心血管死亡、再发心肌梗塞复合终点发生率在两组间差异无显著性(P>0.05)。结论:阿托伐他汀或普伐他汀与负荷剂量氯吡格雷联合治疗急性冠脉综合征安全有效,两组效果相似,无显著差异。     

阿托伐他汀对氯吡格雷抗血小板活性影响的研究

目的:观察阿托伐他汀对氯吡格雷抗血小板活性的影响。方法:29例急性冠脉综合征(ACS)病人被随机分入阿托伐他汀组(n=10)、普伐他汀组(n=9)和对照组(n=10),每组病人均接受阿斯匹林(ASA)、氯吡格雷和低分子量肝素(LMWH)治疗。采用流式细胞仪检测血小板活化指标。结果:治疗3d后,三组血小板活化指标PAC-1和CD62P较治疗前均明显降低,P均<0.05;各组上述两个指标的下降值两两比较均无明显差异,P均>0.05。结论:经细胞色素P4503A4(CYP3A4)途径代谢的阿托伐他汀不抑制氯吡格雷的抗血小板活性。     

不同氯吡格雷代谢型急性心肌梗死患者的血小板聚集率变化

目的观察不同氯吡格雷代谢型急性心肌梗死患者使用氯吡格雷后血小板聚集功能的被抑制情况。方法入选2013年3—8月急性心肌梗死患者48例,经过基因检测分为氯吡格雷慢代谢型6例、快代谢型17例和中间代谢型25例。患者均于入病房前服用负荷剂量阿司匹林300 mg和氯吡格雷300 mg,之后阿司匹林100 mg/d和氯吡格雷75 mg/d连续服用,于服药后第6天检测血小板聚集率、血细胞计数、纤维蛋白原含量和肝肾功能。结果所有患者服用氯吡格雷后第6天的血小板聚集率明显下降,二磷酸腺苷、肾上腺素诱导的抑制率分别为74%和84%。氯吡格雷快代谢型、中间代谢型和慢代谢型3组急性心肌梗死患者的二磷酸腺苷诱导的血小板聚集率分别为22.2%±13.4%、32.1%±20.1%和18.6%±13.9%(P>0.05),3组血小板抑制率分别为87%、78%和82%。结论本研究中不同氯吡格雷代谢型急性心肌梗死患者的血小板聚集功能的抑制情况无明显差异。     

Effect of atorvastatin and pravastatin on platelet inhibition by aspirin and clopidogrel treatment in patients with coronary stent thrombosis

We sought to determine a potential interaction between statins and antiplatelet therapy with aspirin and clopidogrel. Previous laboratory studies have shown a possible drug-drug interaction of statins metabolized by cytochrome P450 3A4 and clopidogrel (prodrug metabolized by cytochrome P450 3A4), resulting in an impaired inhibitory effect of clopidogrel on platelet aggregation. However, conclusive prospective data assessing this potentially relevant interaction are lacking. In 73 patients, 23 with previous coronary stent thrombosis (ST) (ST group) and 50 without coronary ST (control group), platelet aggregation was measured 3 times in monthly intervals using light transmission aggregometry (adenosine diphosphate [ADP] and arachidonic acid induction). Measurements were carried out with aspirin monotherapy (100 mg/day), dual antiplatelet therapy with aspirin plus clopidogrel (75 mg/day), and additional treatment of 20 mg/day of atorvastatin or 40 mg/day of pravastatin. ADP (5 and 20 micromol)-induced platelet aggregation was significantly decreased with clopidogrel (p <0.001) but remained stable under additional treatment with atorvastatin or pravastatin in the 2 groups. Patients with previous ST showed a higher ADP-induced aggregation level than control subjects. This difference was not influenced by clopidogrel or statin treatment. In conclusion, patients with previous ST show a higher aggregation level than control subjects independent of statin treatment. Atorvastatin and pravastatin do not interfere with the antiaggregatory effect of aspirin and clopidogrel. In conclusion, drug-drug interaction between dual antiplatelet therapy and atorvastatin or pravastatin seems not to be associated with ST.     

Influence of statin treatment on platelet inhibition by clopidogrel – a randomized comparison of rosuvastatin,atorvastatin and simvastatin co‐treatment

Objectives. Possible interactions between clopidogrel and atorvastatin, simvastatin or rosuvastatin (a ‘non‐CYP3A4’ metabolized statin) were investigated in a randomized prospective study using sensitive and specific ex vivo platelet function tests. Methods. Patients with coronary artery disease participating in a double‐blind study comparing lipid‐lowering effects of atorvastatin (20–80 mg OD; n = 22) and rosuvastatin (10–40 mg OD; n = 24) were studied before and after 2 weeks treatment with clopidogrel 75 mg OD after completed statin dose titration. In addition, 23 patients were randomized to open‐label simvastatin 40 mg OD. Results. Clopidogrel inhibited 10 μmol L^?1 ADP‐induced platelet aggregation by 40 ± 27%, 57 ± 28% and 51 ± 29%, respectively, in patients on rosuvastatin, atorvastatin and simvastatin treatment. The other platelet tests yielded similar results. No dose‐dependent effects of rosuvastatin or atorvastatin co‐treatment on clopidogrel efficacy were observed. Conclusions. Treatment with CYP3A4 metabolized statins, atorvastatin or simvastatin, did not attenuate the platelet inhibitory effect of clopidogrel maintenance treatment compared with the non‐CYP3A4 metabolized, rosuvastatin.     

急性冠状动脉综合征冠状动脉支架术后应用他汀类药物对氯吡格雷抗血小板作用无影响

目的探讨急性冠状动脉综合征（ACS）患者行冠状动脉支架术后服用阿托伐他汀或普伐他汀对氯吡格雷抗血小板作用的影响。方法研究对象为150例2006年4至12月成功实施冠状动脉支架术的住院ACS患者,术后第1天起随机接受阿托伐他汀20mg／d（n=50）、普伐他汀20mg／d（／7,=50）或无他汀（n=50）治疗。围术期抗血小板治疗为阿司匹林300mg／d,当天氯吡格雷负荷量300mg,继以维持量75mg／d。观测各组患者术后第1天（基线值）及第3天的血小板膜糖蛋白P-选择素（CD62P）、血小板活化复合物（PAC-1）表达及20μmol／L二磷酸腺苷（ADP）诱导的血小板最大聚集率（MPAR）。结果三组患者临床及CD62P、PAC-1和MPAR的基线值差异均无统计学意义。各观测指标第二次测定值与基线值的差值显示,阿托伐他汀、普伐他汀和无他汀组的ACD62P[（4．69±16．78）％、（1．35±10．86）％和（2．97±10．21）％]、APAC-1[（12．78±22．07）％、（8．01±21．23）％和（10．65±21．39）％l及AMPAR[（5．44±18．68）％、（7．15±19．59）％和（3．76±23．42）％]差异均无统计学意义（P〉0．05）。急性心肌梗死患者亚组分析结果表明,ACD62P[（7．50±19．35）％、（3．24±11．18）％和（2．53±8．87）％]、APAC-1[（13．40±24．62）％、（11．28±19．90）％和（10．11±21．29）％]及AMPAR[（7．56±19．11）％、（7．87±23．60）％和（6．75±23．30）％]三组间差异亦均无统计学意义（P〉0．05）。结论接受冠状动脉支架术的ACS患者服用阿托伐他汀或普伐他汀后,短期内未发现对氯吡格雷的抗血小板作用产生显著影响。     

Efficacy of Clopidogrel and Clinical Outcome When Clopidogrel Is Coadministered With Atorvastatin and Lansoprazole: A Prospective,Randomized, Controlled Trial

This prospective, randomized, nonblind, controlled trial evaluated the effects of clopidogrel on platelet function upon coadministration with atorvastatin and lansoprazole.One hundred four adult patients with non-ST-segment elevated acute coronary syndrome (NSTE-ACS) who underwent percutaneous coronary intervention (PCI) with drug-eluting stent implantation were included. All patients were treated with standard dual antiplatelet therapy (DAPT) plus rosuvastatin 10 mg daily after the operation. On the sixth day after PCI, patients were randomly divided into 4 groups, Group A: DAPT + atorvastatin 20 mg daily (a change from rosuvastatin to atorvastatin) + lansoprazole 30 mg daily, Group B: DAPT + atorvastatin 20 mg daily (a change from rosuvastatin to atorvastatin), Group C: DAPT + lansoprazole 30 mg daily (continuing to take rosuvastatin), Group D is the control group. Additional drugs were used according to the situation of patients. Platelet function and concentrations of platelet activation markers (granular membrane protein 140 (P-selectin), thromboxane B2 (TXB2), and human soluble cluster of differentiation 40 ligand (sCD40L)) were assessed before randomization and at 15- and 30-day follow-up visits. All patients were maintained on treatment for 6 months and observed for bleeding and ischemic events.A total of 104 patients were enrolled, 27 patients in group A, 26 patients in Group B/C, 25 patients in Group D separately, and all the patients were analyzed. There were no differences in platelet function and the levels of platelet activation markers (P-selectin, TXB₂, and sCD40L) among or within the 4 groups at the 3 time points of interest (P > 0.05). In the subsequent 6 months, no significant bleeding events occurred, and 12 patients experienced ischemic events, these results were also not significantly different among the groups (P > 0.05).In patients diagnosed with NSTE-ACS who have had drug-eluting stent implantation, simultaneously administering clopidogrel, atorvastatin, and lansoprazole did not decrease the antiplatelet efficacy of clopidogrel or increase adverse event frequency over 6 months.     

Accelerated platelet inhibition by switching from atorvastatin to a non-CYP3A4-metabolized statin in patients with high platelet reactivity (ACCEL-STATIN) study

Aims CYP3A4-metabolized statins can influence the pharmacodynamic effect of clopidogrel. We sought to assess the impact of switching to a non-CYP3A4-metabolized statin on platelet function among patients receiving clopidogrel and atorvastatin with high on-treatment platelet reactivity (HPR). Methods and results Percutaneous coronary intervention (PCI)-treated patients (n= 50) with HPR [20 μM adenosine diphosphate (ADP)-induced maximal platelet aggregation (MPA) >50%] were enrolled during chronic administration of atorvastatin (10 mg/day) and clopidogrel (75 mg/day) (≥6 months). They were randomly assigned to a 15-day therapy with either rosuvastatin 10 mg/day (n= 25) or pravastatin 20 mg/day (n= 25). Platelet function was assessed before and after switching by conventional aggregometry and the VerifyNow P2Y12 assay. Genotyping was performed for CYP2C19*2/*3, CYP3A5*3, and ABCB1 C3435T alleles. The primary endpoint was the absolute change in 20 μM ADP-induced MPA. After switching, MPAs after stimuli with 20 and 5 μM ADP were decreased by 6.6% (95% confidence interval: 3.2-10.1%; P < 0.001), and 6.3% (95% confidence interval: 2.5-10.2%; P = 0.002), respectively. Fifty-two P2Y12 reaction units fell (95% confidence interval: 35-70; P < 0.001) and the prevalence of HPR decreased (24%; P < 0.001). Pharmacodynamic effects were similar after rosuvastatin and pravastatin therapy. In addition to smoking status, the combination of calcium channel blocker usage and ABCB1 C3435T genotype significantly affected the change of 20 μM ADP-induced MPA. Conclusions Among PCI-treated patients with HPR during co-administration of clopidogrel and atorvastatin, switching to a non-CYP3A4-metabolized statin can significantly decrease platelet reactivity and the prevalence of HPR. This switching effect appears similar irrespective of the type of non-CYP3A4-metabolized statin.     

Antiplatelet effects of a 600 mg loading dose of clopidogrel are not attenuated in patients receiving atorvastatin or simvastatin for at least 4 weeks prior to coronary artery stenting.

AIMS: To test prospectively whether the antiplatelet effect of a 600 mg loading dose of clopidogrel is attenuated in patients receiving atorvastatin and simvastatin for at least 4 weeks prior to coronary artery stenting. METHODS AND RESULTS: Blood samples were obtained at least 2 h after receiving 100 mg aspirin and 600 mg clopidogrel and prior to coronary stenting from 90 patients without statin therapy and 90 patients with statin (atorvastatin and simvastatin) therapy for at least 4 weeks. Maximal and residual platelet aggregation was evaluated with optical aggregometry in response to ADP (5 and 20 micromol/l). Surface expression of IIb/IIIa (CD61) and P-selectin (CD62) was assessed with whole blood flow-cytometry at baseline and following stimulation (5 and 20 micromol/l ADP). Inhibition of ADP-induced platelet aggregation was not impaired in the presence of concomitant statin therapy. Moreover, patients with and without statin therapy did not differ in respect to all flow-cytometric parameters obtained. CONCLUSION: The antiplatelet effect of a high, 600 mg loading dose of clopidogrel is not diminished in patients receiving atorvastatin and simvastatin for at least 4 weeks prior to coronary stenting.     

Effects of rosuvastatin on platelet inhibition by clopidogrel in cardiovascular patients

Statin interference has been suggested among the mechanisms of reduction of the antiplatelet effect of clopidogrel. We thus sought to assess the influence of rosuvastatin on clopidogrel antiplatelet action in high-risk (HR) cardiovascular patients. To set the level of platelet inhibition by combined antithrombotic treatments we retrospectively studied two populations of HR patients, one under aspirin alone, the other under aspirin plus rosuvastatin, before and after addition of clopidogrel. The effects of rosuvastatin compared with atorvastatin were then prospectively investigated in patients who underwent percutaneous coronary intervention (PCI), under clopidogrel and aspirin treatment. Light transmission platelet aggregation (LTA) was studied in response to adenosine diphosphate (ADP) (5 μM) or arachidonic acid (0.5 mM). The inhibitory effect of clopidogrel in reducing ADP-induced LTA was similar in the two HR groups of patients. No difference in ADP-induced platelet aggregation was observed in the two PCI groups of patients with either atorvastatin or rosuvastatin. In conclusion, rosuvastatin does not interfere with the antiplatelet effect of clopidogrel in patients with cardiovascular disease.     

Absence of interaction between atorvastatin or other statins and clopidogrel: results from the interaction study

BACKGROUND: Some, but not all, post hoc analyses have suggested that the antiplatelet effects of clopidogrel are inhibited by atorvastatin. We sought to address this issue prospectively by performing serial measurements of 19 platelet characteristics using conventional aggregometry, rapid analyzers, and flow cytometry. METHODS: The Interaction of Atorvastatin and Clopidogrel Study (Interaction Study) was designed for patients undergoing coronary stenting. All patients (n = 75) received 325 mg of aspirin daily for at least 1 week and 300 mg of clopidogrel immediately prior to stent implantation. They had been taking atorvastatin (n = 25), any other statin (n = 25), or no statin (n = 25) for at least 30 days prior to stenting. The main outcome measure was comparison of platelet biomarkers 4 and 24 hours after clopidogrel administration between study groups. RESULTS: At baseline, patients from both statin groups exhibited diminished platelet aggregation and reduced platelet expression of G-protein-coupled protease-activated thrombin receptor (PAR)-1. There were no significant differences in measured platelet characteristics among the study groups 4 and 24 hours after clopidogrel intake, with the exception of a lower collagen-induced aggregation at 24 hours and a constantly diminished expression of PAR-1 in patients treated with any statin. CONCLUSIONS: Statins in general, and atorvastatin in particular, do not affect the ability of clopidogrel to inhibit platelet function in patients undergoing coronary stenting. These prospective data also suggest that statins may inhibit platelets directly via yet unknown mechanism(s) possibly related to the regulation of the PAR-1 thrombin receptors.     

阿加曲班对急性脑梗死患者血小板功能的影响

目的探讨阿加曲班抗凝治疗对急性脑梗死患者血小板功能的影响及其可能的作用机制。方法将急性脑梗死患者60例分为阿加曲班组(30例)和对照组(30例)。2组均给予脑梗死基础治疗。在基础治疗上,阿加曲班组第1、2天给予阿加曲班120 mg/d,48 h持续静脉泵入,第3～7天给予阿加曲班20 mg,2次/d,抗凝治疗结束后加用氯吡格雷75 mg/d;对照组入院后即给予氯吡格雷75 mg/d,持续应用。测定2组治疗前后次日晨、48 h、第7、14天的血小板聚集率(PA),并观察治疗前后血小板计数、活化部分凝血酶时间的变化。结果阿加曲班组治疗后48 h、第7天的PA明显高于治疗前,治疗后第14天的PA明显低于治疗前(P<0.01)。对照组氯吡格雷治疗后次日晨、第7、14天PA明显低于治疗前(P<0.01)。阿加曲班组治疗前同治疗后次日晨、第7天PA差值与对照组治疗前同治疗后次日晨、第7天PA差值比较,差异有统计学意义(P<0.01)。结论急性脑梗死患者应用阿加曲班抗凝治疗时二磷酸腺苷诱导的PA增加。