替罗非班桥接双联抗血小板治疗急性脑梗死临床观察

目的观察早期使用替罗非班桥接拜阿司匹林和氯吡格雷双联抗血小板治疗急性脑梗死的疗效,并评价其安全性。方法回顾性连续纳入2017-10—2018-08长江大学附属第一医院神经内科确诊的128例急性脑梗死患者,依据发病24 h内是否使用替罗非班治疗分为替罗非班组和对照组,共68例纳入替罗非班组,先静脉泵入替罗非班治疗48 h,后过渡为拜阿司匹林和氯吡格雷双联治疗2周。对照组60例仅接受拜阿司匹林和氯吡格雷治疗。2组在治疗第1、3和15天进行美国国立卫生研究院卒中量表(NIHSS)评分和日常生活活动能力量表(ADL)评分,记录2周内颅内出血(包括脑实质出血和脑出血转化)、全身性出血和3个月内死亡发生率。3个月后评估改良的Rankin量表(mRS)评分。根据治疗后3个月mRS评分,将mRS≤2分为预后良好,3≤mRS≤6分为预后不良。结果 2组2周内颅内出血、全身性出血和3个月内病死率差异均无统计学意义(P值分别为0.929、0.827、0.929);治疗第3和15天,替罗非班组NIHSS评分较对照组显著降低(P值分别为0.042和0.016),ADL评分明显升高(P值分别为0.035和0.018)。3个月后,替罗非班组mRS 0～2的比例显著高于对照组(50%vs 31.6%,P=0.027)。结论早期静脉应用替罗非班桥接拜阿司匹林和氯吡格雷双联抗血小板是一种安全、有效的治疗急性脑梗死的方法。     

替格瑞洛的神经科应用：未来路在何方？——急性非致残性脑血管事件高危人群血小板反应性研究的启示

正抗血小板聚集药物在神经科具有广泛的临床应用。阿司匹林作为抗血小板聚集治疗的元老级药物,多项临床研究已经明确其在预防缺血性脑血管病领域的有效性及安全性。氯吡格雷则是继阿司匹林后又一重磅药物,对于神经内科缺血性卒中患者安全有效。除阿司匹林及氯吡格雷外,近年来还有替格瑞洛、西洛他唑、普拉格雷、双嘧达莫、阿西单抗和替罗非班等     

大脑中动脉支架置入后阿托伐他汀对缺血性不良事件的影响：24例12个月随访

背景：血管内支架置入已成为治疗颅内外动脉狭窄的主要方法之一,目前支架置入的安全性和有效性已明显提高,能够明确改善血管狭窄有关的症状及预后,并预防缺血性事件的发生,但仍存在如血栓形成、脑出血、再狭窄以及过度灌注等问题。 目的：探讨阿托伐他汀对大脑中动脉支架置入后缺血性不良事件的影响。 方法：将24例成功完成大脑中动脉支架置入患者随机分为2组,治疗组口服阿托伐他汀40 mg+硫酸氢氯吡格雷75 mg+拜阿司匹林300 mg,1次/d,对照组口服硫酸氢氯吡格雷75 mg+拜阿司匹林300 mg,1次/d,术后1,3,6,12个月以经颅多普勒、数字减影血管造影、核磁共振成像/扩散成像、C-反应蛋白、血脂以及神经专科随访,观察主要的不良事件如支架内再狭窄、短暂性脑缺血发作、脑梗死、再次介入治疗的发生情况。 结果与结论：与对照组比较,治疗组术后1,3,6,12个月血脂及C-反应蛋白水平明显下降(P < 0.05,P < 0.01),缺血性不良事件的发生率明显降低(P < 0.05,P < 0.01)。治疗组术后血脂及C-反应蛋白水平较术前明显降低(P < 0.05,P < 0.01)。同时接受阿托伐他汀治疗的患者均未出现严重的不良反应,说明40 mg是安全的。结果提示可以将他汀类降脂药作为支架置入后的常规治疗,联合抗血小板治疗可以很好的预防支架置入后缺血性不良事件的发生。     

替罗非班在颅内破裂宽颈动脉瘤支架辅助弹簧圈栓塞治疗中的安全性及有效性研究

目的探讨静脉注射替罗非班在支架辅助弹簧圈栓塞治疗急性颅内破裂宽颈动脉瘤中的安全性及有效性。方法选择临沂市人民医院神经外科自2020年1月至2022年9月采用支架辅助弹簧圈栓塞治疗的286例急性颅内破裂宽颈动脉瘤患者为研究对象, 根据抗血小板治疗方案的不同分为双抗组(术前口服负荷剂量阿司匹林及氯吡格雷, 167例)与替罗非班组(术中静脉注射替罗非班, 119例)。应用倾向评分匹配对2组患者年龄、性别、Hunt-Hess分级、高血压史、糖尿病史、吸烟史、动脉瘤位置、瘤径、瘤颈比及支架类型进行匹配后, 统计分析2组患者围手术期出血性及缺血性并发症发生率、出院时神经功能恢复状况[改良Rankin量表(mRS)评分0～2分为恢复良好]的差异。结果 1∶1倾向评分匹配后2组各纳入96例患者进行分析, 其中双抗组患者的出血性并发症发生率(2.1%)与替罗非班组(0.0%)的差异无统计学意义(P>0.05), 双抗组患者的缺血性并发症发生率(9.3%, 包括术中血栓事件8例、术后梗死事件1例)与替罗非班组(7.2%, 包括术中血栓事件6例、术后梗死事件1例)的差异无统计学意义(P>0.05...     

缺血性卒中患者因氯吡格雷低反应性改为高维持量及替格瑞洛后血小板抑制率变化

目的探讨用血栓弹力图评价符合双抗治疗的缺血性脑血管病患者,因氯吡格雷低反应性,改为高维持剂量及改服替格瑞洛后血小板抑制率的变化。方法选择符合双抗治疗的缺血性脑血管病患者联合应用抗血小板制剂(阿司匹林肠溶片100 mg/qd+氯吡格雷75 mg/qd)前及后7 d,用血栓弹力图检测患者的花生四烯酸(AA)和二磷酸腺苷(ADP)途径诱导的血小板抑制率,筛选出氯吡格雷低反应性者96例,随机分为3组,常规剂量组(氯吡格雷75 mg/qd,32例)、高维持量组(氯吡格雷150 mg/qd,32例)和替格瑞洛组(替格瑞洛90 mg/bid,32例),3组阿司匹林继续按原剂量服用。分组后3组按新方案治疗7 d,再次复查血栓弹力图。结果分组后高维持量组及替格瑞洛组ADP诱导的血小板抑制率较常规剂量组有显著性差异(P0.05),3组均未发生出血等严重不良事件,替格瑞洛组发生1例轻度呼吸困难。替格瑞洛组高于同一时间点高维持量组ADP途径诱导的血小板抑制率(P0.05)。结论针对常规剂量氯吡格雷的低反应性,替格瑞洛及双倍剂量的氯吡格雷均能有效降低血小板的高反应性,并且替格瑞洛的作用更为明显,且未增加出血等不良事件的发生。     

经皮腔内冠状动脉成形并支架置入后血管再狭窄的预防及治疗

摘要：经皮腔内冠状动脉成形加支架置入自1977年应用于临床近来得到了迅速发展,目前广泛应用于治疗急性心肌梗死,但是金属支架可导致血栓形成。近年来携带并释放抑制平滑肌细胞增生药物的洗脱支架已应用于临床,可抑制新生内膜增长,降低再狭窄率。药物洗脱支架置入后延迟晚发血栓形成是近年来引起关注的关键问题,所以支架置入后要给予强有力的抗凝治疗。氯吡格雷与噻氯匹定都是有效的抗血小板药物,与噻氯匹定相比,氯吡格雷不良反应小,安全系数更大,起效也更快。联合应用氯吡格雷加阿司匹林预防及治疗经皮腔内冠状动脉成形术加支架置入后再狭窄是安全有效的。随着导管的改进及相关新技术和新疗法的应用,经皮腔内冠状动脉成形术加支架置入的安全性将进一步提高,从而降低再狭窄率。 关键词：支架置入;经皮腔内冠状动脉成形术;药物洗脱支架;氯吡格雷     

不同双联抗血小板治疗时间对FIREBIRD支架置入患者的影响

背景：研究表明，支架内血栓直接影响了药物洗脱支架置入后近远期疗效。 目的：观察分析不同时间的双联抗血小板治疗对Firebird支架置入后冠心病患者心血管不良事件发生率的影响。 方法：选择置入Firebird国产雷帕霉素洗脱支架的患者1 107例，分为阿司匹林+硫酸氯吡格雷3月以内、3~6个月、< 6~12个月组，记录患者心血管不良事件发生率，药物不良反应的发生率及材料宿主反应。 结果与结论：实际随访例数为1 059例(共置入支架1 431枚)，随访时间由7~59个月不等，临床随访率为95.7%。3月以内、3~6个月、< 6~12个月组患者主要心血管不良事件(MACE)发生率分别为8.9%，7.7%，4.4%，差异有显著性意义。3组患者心力衰竭、急性心肌梗死、再次血运重建和主要心脏事件发生率差异均有显著性意义(P < 0.05或< 0.01)，< 6~12个月组发生率最低。各组患者均未发生材料宿主反应。提示，国产Firebird雷帕霉素洗脱支架置入后延长口服氯吡格雷时间至12个月甚至更长患者心血管事件的发生率降低，且不增加药物不良事件的发生率。     

缺血性脑卒中患者阿司匹林或氯吡格雷及其联合应用抗血小板治疗的研究

目的 研究缺血性脑卒中患者阿司匹林或氯吡格雷及其联合应用抗血小板治疗的效果.方法 180例缺血性脑卒中患者分为阿司匹林组(阿司匹林肠溶片100 mg/d)、氯吡格雷组(氯吡格雷75 mg/d)和联合用药组(阿司匹林肠溶片+氯吡格雷,剂量相同);每组60例.在治疗前、治疗14 d后,用血栓弹力图检测患者的花生四烯酸(AA)和二磷酸腺苷(ADP)途径诱导的血小板抑制率.结果 治疗后,3组AA、ADP途径诱导的血小板抑制率显著高于治疗前(均P＜0.05);3组间AA、ADP途径诱导的血小板抑制率的差异有统计学意义(均P＜0.05).联合用药组和阿司匹林组AA途径诱导的血小板抑制率显著高于氯吡格雷组(均P＜0.05);联合用药组和氯吡格雷组ADP途径诱导的血小板抑制率显著高于阿司匹林组(均P＜0.05);联合用药组与阿司匹林组AA途径、联合用药组与氯吡格雷组ADP途径诱导的血小板抑制率的差异无统计学意义.结论 阿司匹林和氯吡格雷对缺血性脑卒中患者均有显著的抗血小板作用;而阿司匹林联合氯吡格雷能从两个途径抑制血小板聚集,抗血小板的效果更好.     

颅外颈动脉支架置入术后抗血小板聚集治疗的对比研究

目的 通过对颅外颈动脉支架置入术后单用阿司匹林或氯吡格雷1年的随访,比较两种抗血小板聚集药物的效果,并比较不同Essen评分组间两种抗血小板聚集药物的疗效。方法 收集2014年1月～2015年1月于重庆医科大学附属第一医院及第三军医大学附属新桥医院接受颅外颈动脉支架置入术的缺血性脑卒中患者219例,术后予以双联抗血小板聚集(阿司匹林100 mg/d及氯吡格雷75 mg/d),应用1个月(69例)或3个月(150例),然后单用阿司匹林(124例)100 mg/d或氯吡格雷(95例)75 mg/d; 并对纳入患者进行Essen评分,分为低危组(41例)及高危组(178例); 随访1年时的主要终点(同侧脑梗死、非同侧脑梗死、心肌梗死、死亡)及次要终点(颅内或颅外出血)。结果 阿司匹林组与氯吡格雷组基线特征均无明显差异。随访1年阿司匹林组主要终点事件同侧脑梗死、非同侧脑梗死、心肌梗死、病死率(分别为2.4%、0.8%、0.8%、0)与氯吡格雷组(分别为1.1%、0、0、0)比较均无明显差异(P>0.05)。阿司匹林组次要终点事件颅内出血、颅外出血发生率(分别为1.6%、3.2%)与氯吡格雷组(分别为1.1%、1.1%)比较亦无明显差异(P>0.05)。Essen评分低危组中阿司匹林组主要终点事件同侧脑梗死、非同侧脑梗死、心肌梗死、病死率(分别为4.3%、0、0、0)与氯吡格雷组(分别为0、0、0、0)比较亦无明显差异(P>0.05); 高危组中阿司匹林组主要终点事件同侧脑梗死、非同侧脑梗死、心肌梗死、病死率(分别为2.0%、1.0%、1.0%、0)与氯吡格雷组(分别为1.3%、0、0、0)比较均无明显差异(P>0.05)。结论 颅外颈动脉支架置入术后双联抗血小板治疗聚集1或3个月再单用阿司匹林或氯吡格雷抗血小板聚集治疗1年内其主要终点事件及次要终点事件发生率无明显差异; 不同Essen评分组间两种抗血小板聚集药物的主要终点事件亦无明显差异。     

急性心肌梗死置入药物洗脱支架与裸金属支架的安全性及即时效应比较

背景：药物洗脱支架越来越多应用于冠状动脉狭窄患者,效果良好。但急诊应用于急性心肌梗死患者的研究报道较少。 目的：对比观察Firebird支架(雷帕霉素洗脱支架)与普通金属裸支架在急性ST段抬高型心肌梗死急诊经皮腔内冠状动脉介入治疗中应用的安全性和临床疗效。 设计、时间及地点：回顾性分析,病例来自2006-01/2008-09洛阳150医院心内科。 对象：选择洛阳150医院心内科收治的ST段抬高型急性心肌梗死行直接经皮腔内冠状动脉介入治疗患者94例,男71例,女23例,年龄47~76岁。 方法：94例患者随机分为2组,Firebird支架组：均在靶病变置入Firebird支架1或2枚;普通支架组：在靶病变置入金属裸支架1或2枚。 主要观察指标：两组患者的安全性、临床疗效及随访情况。 结果：①94例患者介入治疗均获得成功。Firebird支架组52例,共置入68枚药物涂层支架;普通支架组42例,共置入56枚普通支架。两组平均置入支架个数、手术成功率、支架置入并发症发生率、置入前置入后平均狭窄程度及操作时间等差异均无显著性意义(P > 0.05);两组选用的支架内径相比,Firebird支架明显偏小(P < 0.01);两组支架长度相比,Firebird支架显著偏长(P < 0.05)。②住院期间观察两组患者心肌酶峰值,TnI峰值,血管开通后2 h ST段下降幅度,左室功能差异均无显著性意义(P > 0.05)。两组靶血管重建Firebird支架组1例,普通支架组2例,差异亦无显著性意义(P > 0.05)。两组各有2例患者死亡,住院期间心脏事件发生率差异无显著性意义(P > 0.05)。Firebird支架组和普通支架组平均住院时间差异无显著性意义[(11.3±4.2),(12.4±4.6)d,P > 0.05]。③出院后随访1~10个月,平均(6.5±2.4)个月,两组患者无心源性死亡、再梗死。普通支架组心绞痛发生率35.5%较Firebird支架组21.0%显著增高(P < 0.01)。Firebird支架组无心脏事件生存率95%;显著高于普通支架组78%(P < 0.01)。 结论：雷帕霉素药物洗脱支架与普通支架一样在ST段抬高型急性心肌梗死急诊经皮腔内冠状动脉介入中是安全有效的。     

氯吡格雷对不同CYP2C19基因分型脑梗死患者的影响

目的观察氯吡格雷对不同CYP2C19基因分型脑梗死患者血小板CD62P、PAC-1表达和NIHSS评分的影响。方法 56例脑梗死患者根据CYP2C19基因分型分成3组,经氯吡格雷治疗14d,比较3组患者治疗前,治疗后7d、14d的血小板CD62P、PAC-1表达和NIHSS评分的改变。结果 3组患者治疗前血小板CD62P、PAC-1表达和NIHSS评分比较无统计学差异;治疗7d后EM组,IM组的CD62P、PAC-1和NIHSS评分均显著低于治疗前(P0.05),PM组CD62P、PAC-1和NIHSS评分均低于治疗前,但差异无统计学意义(P0.05);治疗14d后,EM组和IM组的CD62P、PAC-1和NIHSS评分均显著低于治疗前(P0.05),也低于治疗后7d(P0.05),PM组的CD62P、PAC-1和NIHSS评分低于治疗前(P0.05),也低于后7d,但差异无统计学意义(P0.05);用药第7天和用药第14天PM组的CD62P、PAC-1表达水平和NIHSS评分均高于EM组(P0.05)。结论脑梗死患者CYP2C19基因形态可能是影响氯吡格雷临床预后的重要影响因素。     

小剂量替罗非班与双抗治疗进展性脑卒中的疗效对比及安全性评价

目的对比替罗非班和双抗治疗进展性脑卒中的疗效,并评价其临床安全性。方法选取2015-07—2016-10我院神经内科确诊的60例急性进展性脑梗死患者,且1周内病情进展,神经功能缺损较前加重。其中28例采用小剂量替罗非班治疗后接受双抗治疗为实验组,32例仅接受双抗治疗为对照组。治疗3d、7d后,比较2组NIHSS评分、BI指数、血小板计数、各项出凝血指标及出血等并发症。结果治疗3d后2组NIHSS评分差异有统计学意义(P0.05),BI指数差异无统计学意义(P0.05);治疗7d后2组间NIHSS评分及BI指数差异有统计学意义(P0.05)。结论替罗非班治疗进展性脑卒中的疗效显著,安全性良好,可提高患者预后质量。     

High post-treatment platelet reactivity is associated with a high incidence of myonecrosis after stenting for non-ST elevation acute coronary syndromes

High post-treatment platelet reactivity (HPPR=adenosine diphosphate [ADP] 10 microM-induced platelet aggregation >70%) identifies low responders to dual antiplatelet therapy with increased risk of recurrent cardiovascular (CV) events after stenting for non-ST elevation acute coronary syndromes (NSTE-ACS). This study was designed to compare the incidence of periprocedural myocardial infarction (MI) after stenting for NSTE-ACS patients between non-responders to dual antiplatelet therapy defined by HPPR and normo-responders. One hundred ninety NSTE-ACS consecutive patients undergoing coronary stenting were included in this prospective study. They received 250 mg aspirin and a 600 mg loading dose of clopidogrel at least 12 hours (h) before percutaneous coronary intervention (PCI). A single post-treatment blood sample was obtained before PCI to analyze maximal intensity of ADP-induced platelet aggregation, and troponin levels were analyzed before PCI, and 12 and 24 h after PCI. Troponin I was considered elevated if >0.4 ng/ml. HPPR was present in 22% of patients (n=42). Periprocedural MI occurred significantly more frequently in patients with HPPR than in the normo-responders (43% vs. 24%, p=0.014). After being correlated with recurrent ischemic events after stenting for NSTE-ACS, the HPPR seems to be also a marker of increased risk of periprocedural MI for NSTE-ACS patients.     

氯吡格雷与阿司匹林联合应用在急性脑梗死治疗中的疗效评定

目的观察急性脑梗死患者血小板上α颗粒膜糖蛋白(CD62p)及溶酶体颗粒膜糖蛋白(CD63)的表达,通过血小板活化的变化,探讨阿司匹林与氯吡格雷联合用药与阿司匹林单药治疗的疗效差异。方法将60例脑梗死患者随机分为两个亚组:单药组(阿司匹林0.15 g/d)和联合用药组(阿司匹林0.10 g/d+氯吡格雷75 mg/d),30例健康体检者为对照组。使用流式细胞术检测所有病例CD62p、CD63阳性率,对单药组和联合用药组治疗前后的CD62p、CD63阳性率进行比较,同时进行NIHSS评分。结果脑梗死组血小板CD62p、CD63阳性率显著高于对照组(P<0.01)。单药组和联合用药组在治疗一周和二周后CD62p、CD63阳性率和NIHSS评分均较治疗前显著下降(P<0.01)。联合用药组治疗二周后与单药组比较CD62p、CD63阳性率和NIHSS评分明显降低,差异有统计学意义(P<0.01)。结论抗血小板治疗对脑梗死有效,阿司匹林+氯吡格雷联合治疗的总体疗效明显优于单用阿司匹林,CD62p、CD63可以衡量抗血小板治疗效果。     

阿司匹林与氯吡格雷双联对TIA患者凝血功能的影响

目的探讨阿司匹林与氯吡格雷双联对短暂性脑缺血发作(TIA)患者血小板聚集率和纤维蛋白原的影响。方法100例短暂性脑缺血发作患者随机分为2组,在常规控制血压、血糖、血脂等基础上,治疗组给予阿司匹林联合氯吡格雷治疗,对照组给予阿司匹林,其中阿司匹林100mg/d,氯吡格雷75mg/d。观察2组血小板聚集率与纤维蛋白原相关指标及临床疗效。结果治疗7~14d后,与对照组比较,治疗组血小板聚集率显著改善(P0.05),纤维蛋白原水平下降更显著(P0.05);治疗组临床疗效显著优于对照组(P0.05)。2组均未出现严重出血并发症。结论阿司匹林与氯吡格雷双联治疗短暂性脑缺血发作可改善患者血小板聚集率,降低纤维蛋白原水平,临床疗效显著。     

Platelet-derived microparticles during and after acute coronary syndrome

As microparticles are shedded upon platelet activation, and may be used to assess platelet function, we measured plasma concentrations of platelet-derived microparticles (PMPs) during and after an acute coronary syndrome (ACS). Fifty-one patients with ACS were investigated at admission, within 24 hours (before coronary angiography), and six months later. Sixty-one sex- and age-matched healthy controls were investigated once. PMPs were defined as particles <1.0 μm in size, negative to phalloidin (labels cell-fragments), and positive to CD61. Exposure of phosphatidylserine (PS+), CD62P and CD142 were also measured. Plasma concentrations of PS+PMPs exposing CD61, CD62P and CD142 were elevated 2.5, 6.0-, and 5.0-fold at admission (p<0.001 for all, compared to controls; aspirin only), decreased significantly 24 hours later following initiation of treatment with clopidogrel and subcutaneous anticoagulation (p<0.001 for all), and decreased even further six months later (p<0.01 for all). However, PS+PMPs exposing CD62P or CD142 were still between 1.2-and 2.3-fold higher than in controls (p<0.001 for both). The pattern for PS-PMPs during and after the ACS was very similar to that for PS+PMPs although the numbers were approximately 1/3 lower. In conclusion, PMP concentrations follow the pattern of platelet activation during and after an ACS. Decreased concentrations are observed after initiation of antithrombotic treatment, but PMP exposing CD62P or CD142 are still elevated after six months. Flow cytometric measurements of PMP in frozen-thawed samples enable studies of platelet function in larger clinical trials.     

阿司匹林联合氯吡格雷治疗进展性脑梗死的疗效观察

目的观察阿司匹林联合氯吡格雷治疗进展性脑梗死的临床疗效。方法将116例进展性脑梗死患者随机分为治疗组58例和对照组58例。2组均采用脑梗死常规治疗,治疗组给予氯吡格雷75mg和阿司匹林300mg,1次/d,连续7d,7d后改为阿司匹林300mg,1次/d,连续7d。对照组单用阿司匹林300mg,1次/d,连续14d。治疗前和治疗14d、30d后进行神经功能缺损程度评分(NIHSS评分),同时评估出血风险。结果治疗组治疗14d和30d后神经缺损评分明显优于对照组,差异有统计学意义。治疗30d后,冶疗组总有效率(89.7%)明显高于对照组(72.4%),差异有统计学意义(P0.05)。2组血小板计数、凝血指标治疗前后对比差异均无统计学意义(P0.05),2组的不良反应发生率无明显差异(P0.05)。结论短期阿司匹林联合氯吡格雷治疗进展性脑梗死可阻止病情进展,降低患者的致残率,且不会增加出血的风险。     

Aspirin platelet reactivity on platelet function and clinical outcome in minor stroke or transient ischemic attack

ObjectiveWhether aspirin platelet reactivity affects platelet function and clinical outcomes with different antiplatelet therapies in patients with mild stroke or transient ischemic attack (TIA) remains unclear. We conducted a subgroup analysis of the PRINCE trial.Materials and methodsPatients with mild stroke or TIA were randomized into aspirin+ticagrelor, or aspirin+clopidogrel groups; aspirin reaction units (ARU) were measured at the baseline and after 7 ± 2 days to assess response to treatment. High on-treatment platelet reactivity (HPR) was defined as ≥550 ARU (poor response to aspirin). The platelet functions of ticagrelor and clopidogrel were measured using the VerifyNow P2Y₁₂ assay for P2Y₁₂ reaction units (PRU); HPR to P2Y₁₂ was defined as >208 PRU (poor response to P2Y₁₂). Clinical outcomes included stroke and clinical vascular and bleeding events after 90 days.ResultsAmong 628 enrolled patients, 69 (11%) were poor aspirin responders. After 7 ± 2 days, the proportion of poor P2Y₁₂ responders for ticagrelor versus clopidogrel significantly reduced in poor (2.6% versus 27.4%) and good (14.3% versus 29.4%) aspirin responders. There were significant interactions between treatment groups, and between treatment groups and aspirin platelet reactivity for poor P2Y₁₂ responders (P = 0.01). After 90 ± 7 days, there were no significant interactions between treatment groups and aspirin platelet reactivity for new stroke risk (good aspirin responders: 5.5% versus 8.8%, hazard ratio [HR]: 0.61; 95% confidence interval [CI], 0.32 to 1.16; P = 0.13; poor aspirin responders: 8.6% versus 8.8%, HR: 0.97, 95% CI: 0.20–4.81; P = 0.97; P for interaction = 0.60). Major bleeding was less frequent in poor than good aspirin responders (ticagrelor/aspirin: 0.4%/0%; clopidogrel/aspirin: 1.4%/0%).ConclusionsIn patients with minor stroke or TIA, clopidogrel, and particularly ticagrelor, decreased platelet function in poor versus good aspirin responders. The poor platelet reactivity of aspirin could not sufficiently reduce the risk of recurrent stroke with ticagrelor or clopidogrel; however, HPR (poor aspirin response) may have a protective effect on clinically relevant major bleeding.     

用血栓弹力图评价阿司匹林及氯吡格雷在缺血性卒中患者中血小板抑制效应的研究

目的用血栓弹力图评价缺血性卒中患者正规使用阿司匹林及氯吡格雷后血小板抑制率的变化。方法血栓弹力图检测我院123例住院患者抗血小板药物治疗后花生四烯酸(AA)通路和ADP受体途径诱导的血小板抑制率,患者抗血小板药物治疗包括阿司匹林组(n=7)、氯吡格雷组(n=8)、阿司匹林+氯吡格联合组(n=108)。结果 123例患者中,阿司匹林组AA诱导的血小板抑率为(87.04±22.71)%,氯吡格雷组ADP诱导的血小板抑制率平均值为(46.61±24.43)%,阿司匹林+氯吡格雷组AA和ADP诱导的血小板抑制率为分别(77.87±27.98)%和(50.23±29.27)%。服用阿司匹林和氯吡格雷的患者分别有115和116例,其AA和ADP途径血小板抑制率分别为(78.42±27.69)%;(49.99±28.88)%,差异具有显著统计学意义(P=0.000)。其中对阿司匹林和氯吡格雷敏感者(血小板抑制率≥50%)分别为97例(84.34%)和89例(75.72%),而不敏感者(血小板抑制率<50%)分别为18例(15.65%)和27例(23.28%),两种药物疗效间差异无显著统计学意义(χ2=3.706,P=0.054)。结论服用100mg/d阿司匹林,在绝大多数缺血性脑血管病患者中能产生较强的血小板抑制效应,而服用75mg/d氯吡格雷对血小板抑制稍弱,但多数患者仍能达有效的血小板抑制作用。     

Pharmacodynamics and pharmacokinetics of the platelet GPIIb/IIIa inhibitor tirofiban in patients undergoing percutaneous coronary intervention: implications for adjustment of tirofiban and clopidogrel dosage

INTRODUCTION: Despite extensive data supporting the use of platelet glycoprotein (GP) IIb/IIIa (GPIIb/IIIa) inhibitors in the therapy of patients with acute coronary syndromes (ACS), there is considerable debate as to the optimal choice of antiplatelet regimen. The objective of this study was to conduct a detailed time-resolved analysis of the effects of the GPIIb/IIIa inhibitor tirofiban with concomitant clopidogrel in ACS patients undergoing percutaneous coronary intervention (PCI) to improve the dosing regimen of these two commonly used antiplatelet drugs. METHODS: The study was performed in 14 patients with non-ST-segment elevation (NSTE) ACS who underwent PCI while being treated with the current typically utilized regimen of tirofiban (10 microg/kg bolus, 0.15 microg/kg/min infusion) and clopidogrel (300 mg). Platelet function was assessed before, during, and after tirofiban infusion using a panel of agonists for ADP receptors, PAR1 and PAR4 thrombin receptors, and collagen receptors. RESULTS: Measurements of circulating tirofiban levels demonstrated a trough, which paralleled a reduction in platelet inhibition for all platelet agonists during the time when PCI was being performed. Interestingly, younger ACS patients (<55 years) exhibited less inhibition of platelet function both during the PCI procedure and after termination of the tirofiban infusion. These apparent age differences were primarily attributed to a decreased responsiveness of the younger patients to clopidogrel. CONCLUSIONS: This study shows that the currently utilized tirofiban dosage is suboptimal and suggests that patients may benefit from a higher dose regimen.