冠脉支架术后阿托伐他汀联用氯吡格雷两药相互作用的随访研究

目的研究在冠脉支架术后随访患者中不同剂量的阿托伐他汀与氯吡格雷长期联用产生的药物相互影响。方法105例冠心病患者,入院第2天随机服用阿托伐他汀和普伐他汀,66例行PC I术者入院当日加服氯吡格雷。共分为5组,A组23例,阿托伐他汀20 mg/d+氯吡格雷,B组20例,阿托伐他汀40 mg/d+氯吡格雷,C组23例,普伐他汀20 mg/d+氯吡格雷,D组20例,单用阿托伐他汀20 mg/d,E组19例,单用阿托伐他汀40 mg/d。分别在入院第1天及出院随访1、3月测定A、B、C组患者的血小板功能指标,并进行比较,测定各组的血脂等指标,分别比较A和D组、B和E组血脂等指标的差异。结果各组患者临床特征基线资料比较,差异无统计学意义;A、B、C组患者首次及随访1、3月测定的血小板功能指标CD62P、CD63、MPAR,组间差异无统计学意义,3组中各指标1、3月比基线均略有所下降（P<0.05）,但1月和3月比较差异无统计学意义,CD62P、CD63、MPAR互为正相关（P<0.05）;A和D组、B和E组在首次及治疗1、3月后相比较,血脂等在两对应组间差异均无统计学意义。结论冠脉支架术后40 mg/d以下的阿托伐他汀与常规剂量氯吡格雷较长时间联用,两药之间相互无明显影响,合用是安全的。     

不同负荷剂量氯吡格雷对血小板聚集率的影响

目的比较两种剂量氯吡格雷的起效时间及安全性,为急性冠状动脉（冠脉）综合征患者用药方案提供依据。方法60例急性冠脉综合征使用不同负荷剂量氯吡格雷患者随机分为A组（300mg）和B组（600mg）,均予氯吡格雷75mg／d后续治疗。以腺苷二磷酸（ADP）5μmol／L及20μmol／L作为诱导剂检测服药前及服药后2h和6h的血小板聚集率,并检测服药前及服药后第3天的血自细胞及血小板计数。结果在ADP20μmoL／L诱导的血小板聚集检测中,两组均显示服药后6h比服药后2h达到更高的血小板聚集抑制水平[A组（29．75±12．11）％比（43．63±14．31）％,P〈0．05;B组（28．86±10．24）％比（34．86±10．84）％,P〈0．05]。B组与A组相比,在服药后2h即起到更加明显的血小板聚集抑制作用[（34．86±10．84）％比（43．63±14．31）％,P〈0．05]。服药后3d内所有人选患者均无出血、自细胞减少及血小板减少等事件发生。结论氯吡格雷600mg作为负荷剂量较之300mg可以更快地达到较高水平的血小板抑制作用,且两者安全性相似。     

氯吡格雷、阿托伐他汀、低分子肝素联合应用治疗急性冠脉综合征疗效观察

目的观察氯吡格雷、阿托伐他汀、低分子肝素联合治疗急性冠脉综合征（ACS）的临床疗效。方法将75例ACS病人随机分为治疗组和对照组。治疗组在对照组常规治疗基础上加服氯吡格雷75mg/d、阿托伐他汀10mg/d;同时皮下注射低分子肝素5000U,每12h1次,连续7d。治疗前后观察心绞痛发作频率、心电图ST段位移、部分活化凝血活酶时间（APTT）等。结果治疗组用药后心绞痛发作频率由（8.3±2.1）次/月减为（1.8±1.4）次/月（P〈0.01）;ST段位移由（1.70±1.13）mm降为（0.37±0.71）mm（P〈0.01）;APTT用药前后比较无统计学意义。对照组治疗前后各指标比较无统计学意义。两组间心绞痛发作频率、ST段位移治疗后比较有统计学意义（P〈0.01）。结论对ACS病人,尽早联合应用氯吡格雷、阿托伐他汀、低分子肝素治疗,可以减少心绞痛发作频率。     

他汀类药对氯吡格雷抗血小板作用的影响

目的 前瞻性评价普伐他汀、氟伐他汀、阿托伐他汀对氯吡格雷抗血小板作用的影响.方法 人选连续1015例急性冠状动脉综合征或稳定性心绞痛行冠状动脉造影和(或)支架术患者,分为普伐他汀组(228例)、氟伐他汀组(179例)、阿托伐他汀组(481例)和对照组(127例).比较各组术后支架内血栓发生率、不同浓度(2、5、10、20 μmol)二磷酸腺苷(ADP)诱导的1 min(ADP-1)、5 min(ADP-5)和最大血小板聚集力(ADP-M)及其影响因素.结果 4组患者基础临床情况(除年龄、高血压及冠状动脉造影复查率外)和冠状动脉病变和(或)支架术情况相似,术后支架内血栓发生率(普伐他汀组0.9%、氟伐他汀组1.1%、阿托伐他汀组1.0%、对照组0.8%,P>0.05)和ADP-1、ADP-5、ADP-M与对照组相比差异均无统计学意义(P均>0.05).多因素回归分析显示,年龄(B=0.21,P=0.001)、氯吡格雷总量(B=7.30,P=0.002)及低分子肝素的使用(OR=6.71,P=0.01)是影响氯吡格雷抗血小板作用的独立决定因素.结论 普伐他汀、氟伐他汀和阿托伐他汀对氯吡格雷的抗血小板作用无明显影响,而年龄、氯吡格雷总量及低分子肝素使用是决定氯吡格雷抗血小板作用的独立因素.     

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。     

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。     

他汀类药物对非ST段抬高的急性冠脉综合征患者血脂及炎性指标的短期影响

目的观察非ST段抬高的急性冠脉综合征（ACS）患者短期应用他汀类药物治疗后血脂、高敏C反应蛋白及纤维蛋白原水平的变化。方法患者均在住院后24h内开始接受药物治疗，他汀组60例（阿托伐他汀组30例、普伐他汀组30例）应用他汀类药物加阿司匹林、氯吡格雷治疗8周，对照组30例单用抗血小板药物，观察三组总胆固醇、低密度脂蛋白胆固醇、高密度脂蛋白胆固醇、高敏C反应蛋白和纤维蛋白原水平的变化。结果治疗8周后，阿托伐他汀组、普伐他汀组胆固醇及炎性指标均有显著变化，两组低密度脂蛋白胆固醇治疗后均达标（P均〈0．05）；而对照组仅高敏C反应蛋白水平显著下降（P〈0．05）。结论他汀类药物与抗血小板药物联用改善冠心病患者血脂及炎性指标效果良好。     

急诊冠状动脉支架术联合国产替罗非班治疗急性ST段抬高性心肌梗死的临床疗效和安全性

目的前瞻性评价急性ST段抬高性心肌梗死（STEMI）患者急诊经皮冠状动脉介入治疗（PCI）联合应用国产替罗非班治疗的临床疗效及安全性。方法入选连续160例接受急诊PCI治疗的急性STEMI患者,随机分为替罗非班组（80例）和对照组（80例）。比较两组基础临床情况、介入治疗结果、术后即刻疗效、术后30天和180天主要心脏不良事件（MACE,包括死亡、再梗死、再次靶血管重建）发生率及左室射血分数（LVEF）。结果两组基础临床情况、介入治疗结果差异均无统计学意义。与对照组相比,替罗非班组术后即刻心肌梗死溶栓试验（TIMI）3级复流血流差异无统计学意义（95．0％比87．5％,P〉0．05）,但即刻心肌组织灌注（TMP）3级（75．0％比56．3％,P〈0．05）、校正TIMI帧数[（23．56±5．19）帧比（31．05±6．92）帧,P〈0．01）]、ST段抬高总和回落[（6．51±3．56）mm比（4．53±2．47）mm,P〈0．01]、肌酸激酶同工酶（CK—MB）峰值[（225．02±105．81）μg／L比（269．20±110．88）μg／L,P〈0．05）、肌钙蛋白Ⅰ（TnⅠ）峰值[（45．25±33．00）μg／L比（56．46±29．48）μg／L,P〈0．05]及平均住院天数[（11．38±4．63）天比（14．68±6．90）天,P〈0．01]均显著优于对照组。替罗非班组术后MACE发生率30天（5．0％比16．3％,P〈0．05）和180天（7．5％比18．8％,P〈0．05）明显降低,LVEF（术后30天：53％±7％比49％±9％,P〈0．01;术后180天：59％±8％比53％±9％,P〈0．01）显著提高。多因素logistic回归分析表明,年龄〉65岁[比值比（OR）=3．42,P〈0．01]、替罗非班治疗（OR=0．56,P〈0．05）、住院期LVEF〈0．5（OR=2．56,P〈0．01）是术后180天MACE发生率的主要决定因素。替罗非班组术后出血并发症发生率高于对照组（16．3％和7．5％）,但差异无统计学意义（P〉0．05）。结论急诊冠状动脉支架术联合应用国产替罗非班治疗STEMI能显著提高相关梗死区域再灌注水平,明显改善术后即刻、术后30天及180天临床预后和左心室收缩功能。     

冠状动脉内应用山莨菪碱对急性心肌梗死介入治疗后无再流及心室功能和收缩同步性的影响

目的探讨冠状动脉内应用山莨菪碱对急性心肌梗死介入治疗（AMI-PCI）后无再流患者的逆转作用并评价其对患者局部、整体心室功能和收缩同步性的影响。方法自2003年1月至2006年2月首发急性前壁心肌梗死并于12h内行急诊PCI的患者136例,根据心肌灌注分级方法（myocardial blush grade,MBG）确认无再流患者（MBG0-1级）47例（男36例,女11例）,平均年龄（63．23±11．24）岁,随机分为两组：A组（山莨菪碱组,24例）和B组（对照组23例）,A组于PCI后即刻由指引导管冠状动脉内注射山莨菪碱1000斗g／次,余治疗同B组。于PCI后即行左心室造影,测定心室容积、压力参数和室壁运动积分（wall motion score,WMS）;AMI后1周时行平衡法核素心室造影,测定左室整体和局部收缩功能、舒张功能和收缩同步性参数;AMI后6个月随访时重复行心室造影和核素心室造影检查测定上述参数,同时随访并记录术后6个月内主要不良心脏事件（MACE）的发生率。结果（I）A组患者在冠状动脉内应用山莨菪碱1000μg／次,平均（2．53±0．34）次后MBG由（0．74±0．32）级增加到用药后的（2．33±0．28）级。（2）AMI-PCI后6个月随访时,A组左室收缩末容积指数、左心室舒张末期容积指数、WMS和左室舒张末期压均较B组明显降低[（40．53±8．12）mL／m^2比（50．32±8．26）mL／m^2,（80．13±9．74）ml／m^2比（87．17±10．25）mL／m^2,（8．24±1．31）比（10．23±1．82）,（13．36±4．21）mmHg（1mmHg=0．133kPa）比（16．38±3．21）mmHg,P均〈0．05];核素心室造影参数比较,A组左室射血分数、峰射血率和峰充盈率等参数均较B组明显增加I（44．02±5．86）％比（38．52±5．18）％,（1．86±0．09）EDV／s比（1.61±0．09）EDV／s,（2．19±0．32）EDV／s比（1.78±0．17）EDV／s,P均〈0．05]。（3）A组AMI-PCI后6个月左室局部射血分数（LrEF）2-LrEF8均分别较B组增加13．96％、25．02％、30．36％、22．86％、27．67％、22．07％和18．71％（P均〈0．05）.（4）相位分析示A组左室收缩同步性参数相角程、半高宽和峰相位标准差亦均低于B组[（46．04±8．93）°比（53．19±16．62）°,P〈0．05;（23．02±6．27）°比（25．02±5．31）°,P〉0．05;（7．92±4．12）°比（11．76±4．11）°,P〈0．05]。（5）在6个月随访期内,A组MACE发生率明显低于B组。结论冠状动脉内注射山莨菪碱可明显逆转AMI-PCI后无再流现象,改善无再流患者的心室功能和收缩同步性,降低MACE发生率。     

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。     

冠状动脉支架术后三联抗血小板药物治疗对血小板功能的影响

目的探讨三联抗血小板药物治疗对冠状动脉(冠脉)支架术后患者血小板活化和聚集功能的影响。方法120例冠心病行冠脉支架植入术患者,随机分为三联组(阿司匹林、氯吡格雷和西洛他唑)和两联组(阿司匹林和氯吡格雷),三联组于术后第1天起加服西洛他唑。两组分别于术后第1天服用西洛他唑前及第5天测定血小板活化复合物(PAC-1)和CD_(62)p,同时测定5μmol/L及20μmol/L ADP诱导的血小板最大聚集率(MPAR)。结果两组临床基线资料及CD_(62)p、PAC-1和MPAR基线值差异均无统计学意义。分别计算各指标第二次测定值与基线值的差值,两组ΔMPAR差异无统计学意义,但三联组和两联组ΔCD_(62)p和ΔPAC-1分别为[(5.12±11.25)%比(1.08±4.97)%,P＜0.05]和[(12.12±12.30)%比(2.22±15.15)%,P＜0.01]。对急性冠脉综合征(ACS)患者亚组分析结果表明三联组ΔMPAR(5μmol/L)[(8.68±10.35)％比(2.92±13.06)%,P=0.018]、ΔMPAR(20μmol/L)[(11.05±11.14)%比(5.16±13.27)%,P=0.019]、ΔCD_(62)p[(5.57±12.08)％比(1.35±4.42)%,P=0.028】和ΔPAC-1[(11.62±12.73)%比(1.29±15.73)%,P= 0.001]均显著高于两联组。3个月临床随访显示三联组与两联组主要不良心、脑血管事件发生率分别为0和3.3%(2/60),出血发生率分别为5%(3/60)和3.3%(2/60),均无统计学意义。结论三联抗血小板药物治疗与常规两联治疗相比能更有效地抑制冠脉支架术后血小板活化和聚集,但其疗效和安全性还需大规模临床试验证实。     

急性冠状动脉综合征患者血小板膜糖蛋白Ⅱb/Ⅲa和P选择素水平的变化

目的探讨急性冠状动脉综合征(ACS)患者血小板聚集功能及抗血小板治疗对其影响。方法入选ACS患者40例,分为不稳定型心绞痛组(26例)和急性心肌梗死组(14例),采用流式细胞术测定ACS患者应用阿司匹林及氯吡格雷抗血小板治疗前后血小板膜糖蛋白(GP)Ⅱb/Ⅲa(PAC-1)和P选择素(CD62P)水平的变化,并与疑诊冠心病但冠状动脉造影检查正常的对照组(30例)进行比较。结果治疗前,不稳定型心绞痛和急性心肌梗死患者PAC-1、CD62P的表达率(%)均高于对照组(PAC-1:62.47±3.91和67.91±10.42比32.46±8.93;CD62P:16.73±3.74和18.53±5.62比7.67±2.21,均为P<0.05),经双重抗血小板治疗5 d后,两组PAC-1、CD62P的表达率(%)较治疗前均明显降低(PAC-1:43.62±9.67比62.47±3.91,46.55±4.86比67.91±10.42,均为P<0.05;CD62P:12.38±3.29比16.73±3.74,13.39±3.41比18.53±5.62,均为P<0.05),但仍高于对照组(均为P<0.05)。结论 ACS患者应用阿司匹林及氯吡格雷双重抗血小板治疗,可有效抑制血小板活化。     

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.     

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.     

急性冠状动脉综合征合并肾功能不全的支架术治疗

目的　评估急性冠状动脉 (冠脉 )综合征合并肾功能不全患者经皮腔内支架术的预后。方法　 6 3例急性冠脉综合征合并肾功能不全行冠脉内和或肾动脉支架植入术患者 (肾功能不全组 ) ,随机选取同期 6 3例一般情况匹配 ,肾功能正常行介入治疗患者 (对照组 )。比较两组临床特征、血管造影、支架术及随访情况。结果　肾功能不全组患者血清肌酐水平显著增高 [(177± 31) μmol/L比(98± 2 1) μmol/L ,P <0 0 0 1]、左室射血分数减低 (0 4 5± 0 10比 0 5 0± 0 0 9,P <0 0 5 ) ,冠脉多支病变增多 (84 %比 6 5 % ,P <0 0 5 )且肾动脉狭窄发生率显著增高 (2 7%和 8% ,P <0 0 5 ) ,13例患者在冠脉支架术同时行肾动脉支架术 (比较对照组 2例 ,P <0 0 5 ) ;两组冠脉支架术手术成功率和术中并发症相似 ;随访表明 ,肾功能不全组严重心脏不良事件发生率较高 (13%和 8% ,P =0 38) ,平均血清肌酐水平较术前降低 (177± 31μmol/L和 14 7± 11μmol/L ,P <0 0 5 ) ,9例 (6 9% )肾动脉狭窄患者肾动脉支架术后血清肌酐恢复正常。结论　急性冠脉综合征合并肾功能不全患者冠脉支架术安全、有效 ,2 / 3接受肾动脉支架术患者术后血清肌酐恢复正常。     

Serial changes in platelet activation in patients with unstable angina following coronary stenting: evaluation of the effects of clopidogrel loading dose in inhibiting platelet activation.

BACKGROUND: Platelet activation is crucial in the development of acute or subacute stent thrombosis following implantation. This study investigated whether a conventional regimen comprising a loading dose of 300 mg of clopidogrel, followed by daily doses of 75 mg, could significantly suppress platelet activation in patients with unstable angina (UA) undergoing coronary stenting. METHODS AND RESULTS: Platelet activation (expressed by CD62p) was serially examined using flow cytometry in 42 consecutive patients with UA who underwent coronary stenting. CD62p expression was also evaluated in 30 normal control subjects. CD62p expression was markedly higher pre-procedure in the study patients than in the normal control subjects (5.2+/-4.0% vs 1.4+/-0.6%, p<0.0001). CD62p expression in the study patients remained significantly higher at 24 h after the procedure than in the control subjects (3.8+/-2.1% vs 1.4+/-0.6%, p<0.001). Additionally, only 26% of CD62p expression (5.2% vs 3.8%, p=0.026) in the study patients was suppressed at 24 h after the procedure. However, more than 60% of CD62p expression (5.2% vs 2.0%, p<0.0001) was suppressed on day 7 after the procedure. CONCLUSION: Less than one-third of CD62p expression was suppressed at 24 h by the conventional loading dose (300 mg) of clopidogrel in patients with UA following coronary stenting. This finding indicates the need to evaluate whether an increased loading dose of clopidogrel would be a more efficacious and safe regimen for patients in this clinical setting.     

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.     

冠心病介入手术后阿托伐他汀对冠脉再狭窄的影响

目的：观察经皮冠状动脉介入（PCI）术后患者服用阿托伐他汀后血清低密度脂蛋白-胆固醇（LDL—C）水平达标情况及其与冠脉再狭窄的关系。方法：选择我院因冠心病行PCI术患者91例,术后除接受抗血小板等常规治疗外,均服用阿托伐他汀（20mg／d）,6～18月后再次行冠脉造影术（CAG）,根据CAG评分结果患者被分为病变进展组（n=32）和病变未进展组（n=59）;又根据第二次手术前LDL—C水平分为LDL-C≥2．1mmol／L（n=43）,1．64LDL—c〈2．1mmol／L（n=30）,LDL—C〈1．6mmol／L（n=18）三亚组,并探讨其相关性。结果：与病变未进展组患者比较,病变进展组LDL-C降低幅度[（0．46±0．81）mmol／L比（-0．04±0．65）mmol／L],降低百分比[（13．18±31．67）％比（-8．21±37．22）％]明显减小（P均〈0．05）;LDL-C≥2．1mmol／L组,1．6≤LDL-C〈2．1mmol／L组,LDL-C〈1．6mmol／L组病变未进展者比例逐渐升高（58．1％比63．3％比83．3％,P〈0．05）;Spearman分析显示,CAG前LDL水平与冠脉评分呈负相关（r=-0．70,P〈0．0001）。结论：常规治疗量的阿托伐他汀可使多数患者低密度脂蛋白胆固醇水平达标并有效遏制冠心病患者冠脉再狭窄。