海南省缺血性脑卒中二级预防中抗血小板药物治疗的现状及影响因素分析

目的调查分析缺血性脑卒中二级预防中抗血小板药物的使用现状及影响因素。方法入选海南省10家综合性医院再次住院的缺血性脑卒中患者1300例,调查患者入院时抗血小板药物的应用状况,采用单因素及多因素logistic回归模型对资料进行分析。结果缺血性脑卒中患者抗血小板治疗知晓率为60.4%,治疗率为49.2%。多因素logistic回归分析显示,教育程度、医疗保险、健康教育是患者服用抗血小板治疗的独立危险因素。结论缺血性脑卒中二级预防中抗血小板治疗现状令人堪忧,临床医师需提高认识,加强对脑卒中患者的健康教育,建议患者长期服药,提高脑卒中后抗血小板治疗的知晓率及治疗率。     

缺血性脑卒中二级预防治疗的依从性研究

目的采取有效措施减少缺血性脑卒中再发,对缺血性脑卒中或短暂性脑缺血发作(TIA)患者采取ABCDE策略,观察患者出院后1年能否维持高水平药物治疗符合率。方法选择缺血性脑卒中或TIA患者178例,采取ABcDE策略进行规范的二级预防。观察患者出院时及出院后1年二级预防中抗血小板、降压、降糖和他汀类药物治疗的符合率。结果 178例患者中既往有缺血性脑卒中或TIA史126例,其住院前抗血小板治疗比例为41.3%,服用降压、降糖和他汀类药物治疗比例分别为89.9%、83.3%和13.5%;155例完成出院1年随访,降压治疗符合率为100%,抗血小板治疗符合率为97.2%,降糖和他汀类药物治疗符合率为98.2%和84.3%。结论采取ABCDE策略对缺血性脑卒中或TIA患者进行规范干预后,明显缩小二级预防循证证据与临床实践之间的差距,患者出院1年药物治疗符合率维持在较高水平。     

缺血性脑卒中患者CAS术后药物治疗的研究进展

近年来国内缺血性脑卒中患者日益增多,颈动脉狭窄为其主要病因之一。颈动脉支架成形术（CAS）为目前治疗颈动脉狭窄的主要方法之一,但术后出现的支架内血栓形成和再狭窄临床处理棘手。研究显示,抗血小板聚集、抗血栓形成及稳定动脉粥样硬化斑块可降低CAS后支架内再狭窄的发生,其中拜阿司匹林、     

治疗脑卒中的新疗法

综合治疗可能对脑卒中的治疗更加理想,因为缺血性脑卒中是卒中类型当中最常见的,同时缺血性脑卒中由于一条或多条血管突然暂时性或永久性受到血栓形成或栓塞阻塞,而引起肢体运动和感觉障碍,不能讲话等一系列由于神经支配范围。过去缺血性脑卒中用 rTPA 溶栓治疗,目的就是想让血流再通,使血供比较通畅,使恢复肢体运动或感觉,但遗憾的是这种治疗方法并不适合每一个脑卒中患者,总体效     

经皮冠状动脉介入术合并脑出血患者的抗栓治疗策略

正抗栓治疗包括抗血小板治疗及抗凝治疗,能够有效防止PCI后患者发生支架内血栓形成和再发缺血事件,但同时增加了局部及全身出血并发症的风险。PCI后合并脑出血虽然发生率低,但病死率、致残率较高,是PCI围术期最严重的并发症之一。一旦发生脑出血,若继续应用抗栓药物会进一步增大急性期血肿面积,而停用抗栓治疗可能引发的心肌梗死或缺血性脑卒中等血栓事件,同样会危及生命。本综述结合近期国内外相关研究和指南,就PCI后合并脑出血的抗栓治疗策略及其预防进行     

氯吡格雷在预防缺血性事件中的作用评价

缺血性事件 (缺血性脑卒中、心肌梗死、血管性死亡 )是临床上动脉血栓形成性疾病患者的主要死亡原因 ,要改善这类患者的预后 ,减少死亡率 ,防治血栓形成就显得极为重要。而血小板活化在血栓形成中具有重要作用 ,故临床上常用包括抗血小板药在内的综合措施预防缺血性事件的发生。临床试验表明 ,阿司匹林———血栓素途径抑制剂 ( 75～ 32 5mg/d )和噻氯匹啶———ADP受体拮抗剂 ( 2 5 0mg ,bid)均为有效抗血小板药物 ,能显著减少缺血性事件的发生。但两者均因具有严重的不良反应而在临床应用中受到限制。血小板糖蛋白Ⅱb/Ⅲa抑制剂静脉用于…     

血小板受体作为抗血小板治疗靶点的研究进展

正血小板在血栓形成过程中发挥着重要的作用。作用于血小板黏附,聚集等过程的抗血小板药物能有效地抑制体内血栓形成,预防和治疗急性冠脉综合征和缺血性脑卒中,抑制动脉粥样斑块破裂后的血栓形成,预防支架血栓形成。抗血小板治疗的作用靶点很多,本文主要对血小板上二磷酸腺苷受体,蛋白激酶受体,膜糖蛋白受体,血栓烷A2受体等受体及其拮抗剂的临床研究进展进行综述。1血小板的功能及血小板膜受体的类型血小板的黏附、聚集、释放在动脉内血栓形成的过程中发挥     

2008年AHA／ASA预防缺血性脑卒中或短暂性脑缺血发作患者再发卒中建议的更新

美国心脏病协会／美国脑卒中协会（AHA／ASA）预防脑卒中和短暂性脑缺血发作（TIA）患者再发脑卒中写作委员会对相关建议（2006年）公布后，近期发表的临床研究结果进行了综合分析和回顾。本文重点在于对新的资料进行简短回顾，更新部分推荐意见，并说明修改的理由。最新的临床试验主要涉及两个方面：①对非心源性血栓栓塞性缺血性脑卒中或TIA患者，应用特异性抗血小板药物预防再发脑卒中；②应用他汀类药物预防再发脑卒中。     

活化血小板在缺血性脑卒中病理机制中的作用研究进展

<正>缺血性脑卒中是临床常见的血栓相关疾病,血小板活化是其重要的病理机制之一。早期的血小板黏附和激活可引起血栓-炎症级联反应,甚至并不一定需要发生血小板聚集和血栓形成,在缺血性脑卒中发生后的缺血再灌注损伤过程中,血小板更多的是扮演炎性介质的角色,而临床应用抗血小板药物可减轻炎症分子的表达[1-2]。现就近年来血小板活化在缺血性脑卒中病理机制中的作用研究进展做一综述。1血小板膜糖蛋白(GP)Ⅰb和GPⅥ     

支架术后患者非心脏手术的围术期抗血小板治疗

目前越来越多的患者接受冠状动脉造影及冠脉支架植入术,冠状动脉支架术后双重抗血小板治疗成为冠心病支架术后防止血栓形成及再发心肌梗死的重要手段,但支架植入术后非心脏手术及侵入性操作会增加血栓形成的风险,医生不得不面临术前停用双重抗血小板治疗避免出血及围术期血栓形成的两难境地.基于此,既往回顾性的研究表明停用抗血小板治疗产生...     

Novel Anti-platelet Agents: Focus on Thrombin Receptor Antagonists

Platelets are the key in the pathogenesis of atherothrombotic disease such as acute coronary syndromes, stroke, and peripheral arterial disease. Current anti-platelet treatments are mainly based on inhibition of two important pathways of platelet activation: thromboxane A2 (TXA2) mediated (aspirin) and adenosine diphosphate (ADP)–P2Y12 receptor mediated (clopidogrel, prasugrel, and ticagrelor). Despite the dual anti-platelet therapy with aspirin and P2Y12 inhibitors have reduced ischemic events in patients with acute coronary syndromes (ACS), the rate of recurrent ischemic complication after ACS remains high. Combination of multiple anti-platelet agents is also associated with increased risk of bleeding. Thrombin is a potent platelet agonist and the increase of its activity has been reported in patients with ACS. Platelet effects of thrombin are mediated by protease-activated receptors (PAR), and PAR-1 is the most important receptor in human platelets. Two PAR-1 antagonists, vorapaxar and atopaxar, have undergone clinical investigation. In this review, we will describe the pharmacology of PAR-1 antagonists and will review and discuss results of randomized clinical trials with PAR-1 antagonists.     

Increased risk in patients with high platelet aggregation receiving chronic clopidogrel therapy undergoing percutaneous coronary intervention: is the current antiplatelet therapy adequate?

OBJECTIVES: We sought to determine whether patients receiving chronic clopidogrel therapy undergoing nonemergent stenting who display high on-treatment preprocedural platelet aggregation measured by standard light transmittance aggregometry and thrombelastography (TEG) will be at increased risk for poststenting ischemic events. BACKGROUND: Patients exhibiting heightened platelet reactivity to adenosine diphosphate (ADP) might be at increased risk for recurrent ischemic events after coronary stenting. METHODS: A total of 100 consecutive patients receiving chronic antiplatelet therapy consisting of aspirin (325 mg qd) and clopidogrel (75 mg qd) were studied before undergoing nonemergent stenting. Patients were followed for 1 year after coronary stenting for the occurrence of death, myocardial infarction, stent thrombosis, stroke, or ischemia requiring a hospital stay. RESULTS: All patients were aspirin responsive. Patients with ischemic events (23 of 100, 23%) within 1 year had greater on-treatment prestent ADP-induced platelet aggregation than patients without ischemic events by aggregometry and TEG (p < 0.001 for both measurements). Of patients with an ischemic event, 70% and 87% displayed high on-treatment platelet reactivity at baseline by aggregometry and TEG, respectively. High on-treatment platelet reactivity as measured by aggregometry and TEG were the only variables significantly related to ischemic events (p < 0.001 for both assays). The administration of eptifibatide reduced periprocedural elevation in platelet reactivity, with no significant differences in bleeding events. CONCLUSIONS: Patients receiving chronic clopidogrel therapy undergoing nonemergent percutaneous coronary intervention who exhibit high on-treatment ADP-induced platelet aggregation are at increased risk for postprocedural ischemic events. These findings might have implications for the alteration in clopidogrel maintenance dose and use of glycoprotein IIb/IIIa inhibitors in selected patients.     

Changing common sense:Anti-platelet/coagulation therapy against cirrhosis

Until recently,anti-platelet/coagulation therapy had not been recommended for patients with cirrhosis.Although venous thrombosis is one of the representative complications of cirrhosis and ischemic disorders associated with atherosclerosis are not infrequent in cirrhotic patients,many clinicians have tended to hesitate to introduce anti-platelet/coagulation therapy to their patients.Undoubtedly,this is due to the increased risk of hemorrhagic diathesis in cirrhotic patients.However,accumulating evidence has revealed the benefits of anti-platelet/coagulation therapy for cirrhotic patients.In addition to the safety of the therapy carried out against cardiovascular diseases in cirrhotic patients,some clinical data have indicated its preventive effect on venous thrombosis.Moreover,the efficacy of antiplatelet/coagulation therapy against cirrhosis itself has been demonstrated both clinically and experimentally.The conceptual basis for application of anti-platelet/coagulation therapy against cirrhosis was constructed through two pathologic studies on intrahepatic thrombosis in cirrhotic livers.It may be better to use thrombopoietinreceptor agonists,which have been tested as a treatment for cirrhosis-related thrombocytopenia,in combination with anti-platelet drugs to reduce the risk of venous thrombosis.During the last decade,the World Journal of Gastroenterology,a sister journal of World Journal of Hepatology,has been one of the main platforms of active discussion of this theme.     

颈动脉支架置入术后3年随访结果分析

目的探讨颈动脉支架置入术(CAS)在预防脑梗死方面的远期效果。方法选择接受颅外段CAS患者55例,定期随访3年。根据CAS后发生缺血性脑血管事件(4例)和未发生缺血性脑血管事件(51例)进行比较。并分析CAS后血管再狭窄情况。结果在55例完成3年随访的CAS患者中,4例(7.3%)出现了终点事件的患者均为脑梗死。其中3例患者缺血事件对应的脑梗死在支架置入同侧,1例患者缺血事件对应的脑梗死在支架置入对侧。单因素分析发现,年龄>75岁、高血压史、有两个以上脑血管病危险因素、术后未系统服用抗血小板药物、术前有多次脑梗死病史的患者术后容易发生缺血性脑血管事件(P<0.05)。3年随访观察,有3例(5.5%)发生了再狭窄。结论 CAS能有效降低动脉粥样硬化性颈动脉狭窄患者脑卒中发生风险。CAS后中远期再狭窄率较低。     

Antiplatelet treatment of cardiovascular disease: a translational research perspective

Platelet mediated thrombosis is the primary cause of ischemic event occurrence in patients with cardiovascular disease. The P2Y12 receptor plays a central role in thrombus generation and is therefore a major target for pharmacologic therapy. Although various clinical trials have demonstrated the efficacy of dual antiplatelet therapy with aspirin and clopidogrel, recurrent ischemic events occur in approximately 10% of patients with acute coronary artery syndromes. Recent translational research studies have explored the various limitations of dual antiplatelet therapy including wide response variability and resistance. The association of ischemic event occurrence with high on-treatment platelet reactivity to adenosine diphosphate has been reported in recent small studies suggesting that the latter may be a quantifiable and modifiable risk factor. Recent studies have identified a potential therapeutic target for P2Y12 inhibitors that may influence the future development of personalized antiplatelet treatment strategies aimed at the reduction of ischemic event occurrence in high risk patients. Finally, based on the current evidence platelet reactivity may become a standard of care risk factor measured in all patients with cardiovascular disease.     

缺血性脑卒中复发与相关因素分析

目的观察缺血性脑卒中患者2年复发率及复发的相关危险因素。方法采用前瞻性的队列研究方法,共纳入首发缺血性脑卒中患者860例,根据2年随访是否复发分为复发组(106例)和无复发组(754例)。并按照TOAST标准进行病因分型,大动脉粥样硬化型(LAA)261例,小动脉闭塞型(SAO)186例、心源性栓塞型(CES)191例、其他明确病因或不明原因型(UND)222例,随访2年,观察不同病因分型脑卒中复发率的差异,并进行多因素回归分析相关因素。结果复发组年龄、高血压、糖尿病、吸烟及纤维蛋白原水平较无复发组明显升高(P<0.05,P<0.01);抗血小板药物依从性较无复发组明显降低,差异有统计学意义(P<0.01)。复发脑卒中106例,其中LAA 29例,SAO 22例,CES 36例,UND 19例。多因素回归分析显示,年龄、高血压史、糖尿病史、纤维蛋白原、TOAST分型及抗血小板药物依从性与缺血性脑卒中复发相关。结论不同病因型脑卒中2年复发率存在差异;纤维蛋白原、TOAST病因分型及抗血小板药物依从性也是缺血性脑卒中复发的独立危险因素。     

踝肱指数联合头颈部CT血管造影在缺血性卒中复发的预测价值

目的 探讨踝肱指数（ABI）联合头颈部CT血管造影(CTA)在缺血性卒中复发的预测价值。方法 选取广东医学院附属深圳福田人民医院神经内科于2009年1月至2011年12月缺血性卒中住院患者共465例,测量所有患者的ABI和头颈部血管CTA,观察患者出院2年内缺血性卒中复发的发生情况,对缺血性卒中复发相关危险因子进行 Logistic多因素回归分析。结果 随访2年内复发患者为102例,复发次数≥1次。随访结果发现,低ABI、颅内外动脉狭窄是缺血性卒中患者复发的独立预测因子（P值分别为0.015,0.001）;复发组ABI＜0.9的患者的比率显著高于未复发组（P=0.017）;复发组有颅内外动脉狭窄的患者的比率显著高于未复发组（P=0.001）;复发组 ABI＜0.9且有颅内外动脉狭窄的患者的比率显著高于未复发组（P<0.05）。结论 ABI及头颈部CTA改变对缺血性卒中的复发风险具有预测价值,且二者联合的预测价值更好,ABI<0.9且有颅内外动脉狭窄的缺血性卒中患者更易复发。低ABI、颅内外动脉狭窄是缺血性卒中患者复发的独立预测因子。     

有缺血性卒中史的冠心病患者经皮冠状动脉介入治疗的长期疗效

目的 探讨接受经皮冠状动脉介入治疗(PCI)且既往有缺血性卒中史的冠心病患者的临床特点和长期随访的结果.方法 回顾性分析北京协和医院2003年1月至2007年12月连续行PCI的2053例患者的临床资料,并随访至2009年12月.随访终点事件包括全因死亡、心原性死亡、支架内血栓形成、靶病变再次血管重建、再次心肌梗死、脑梗死.统计随访期间患者主要出血事件的发生率.结果 共随访1945例冠心病患者,其中222例患者既往有缺血性卒中病史.与非缺血性卒中患者比较,有缺血性卒中史患者的年龄较大(P =0.000),高血压患病率(P=0.000)、糖尿病患病率(P =0.005)和多支病变(P=0.000)比例较高.患者随访时间为(35.0±19.6)个月.与非缺血性卒中患者比较,有缺血性卒中史患者的心原性死亡(8.5％比3.9％,P =0.002)、再次脑梗死(5.8％比1.4％,P =0.000)的发生率较高,服用双联抗血小板时间差异无统计学意义[(13.77±11.33)个月比(13.94±11.33)个月,P=0.986],主要出血事件的发生率差异无统计学意义(5.8％比3.6％,P=0.100),而脑出血的发生率较高(1.8％比0.5％,P=0.028).结论 与非缺血性卒中患者比较,既往有缺血性卒中史的冠心病患者有更高的危险因素患病率,冠状动脉受累的部位更多,随访期间心原性死亡和再次脑梗死的发生率更高,在不减少双联抗血小板治疗时间的情况下脑出血的发生率更高.     

Design of the blockade of the glycoprotein IIb/IIIa receptor to avoid vascular occlusion (BRAVO) trial

BACKGROUND: Platelets play a key role in the pathogenesis of atherosclerosis, thrombosis, and acute coronary and cerebrovascular syndromes. Inhibition of platelet function by acetylsalicylic acid (aspirin) has been shown to reduce the incidence atherothrombotic events in patients with coronary, cerebrovascular, or peripheral vascular disease. Thienopyridine agents, however, including ticlopidine and clopidogrel, inhibit the adenosine diphosphate receptor and have modestly superior effects compared with aspirin on reduction of death, myocardial infarction, and stroke among a broad group of patients with vascular disease. More effective antithrombotic agents are still required to treat patients at high risk for recurrent vascular events. METHODS: Lotrafiban, a selective, nonpeptide antagonist of the human platelet fibrinogen receptor (glycoprotein [GP] IIb/IIIa [alphaIIb/beta3 integrin]), blocks the binding of fibrinogen to the GP IIb/IIIa receptor, which is the final common pathway of platelet aggregation. Lotrafiban at doses of up to 50 mg twice daily was well-tolerated in a 12-week, double-blind, placebo-controlled, dose-ranging study in patients with recent myocardial infarction, unstable angina, transient ischemic attack, or stroke when added to aspirin therapy. On the basis of these results, a dosing regimen was selected for the phase III Blockage of the Glycoprotein IIb/IIIa Receptor to Avoid Vascular Occlusion (BRAVO) trial based on pharmacodynamics and drug tolerability. In the pivotal BRAVO study, lotrafiban therapy is being evaluated in patients who have had a recent myocardial infarction, unstable angina, transient ischemic attack, or ischemic stroke, or who present at any time after a diagnosis of peripheral vascular disease combined with either cardiovascular or cerebrovascular disease. RESULTS: The efficacy evaluation will be based on a composite end point of clinical events (death by any cause, myocardial infarction, stroke, recurrent ischemia requiring hospitalization, or urgent ischemia-driven revascularization). The target enrollment is 9200 patients worldwide. Approximately 700 centers will participate and will be distributed within 30 countries across North America, Europe, Australia, and Asia.     

Platelet function monitoring in patients on clopidogrel: What should we learn from GRAVITAS?

Combined inhibition of platelet aggregation is essential to prevent recurrent ischemic episodes in patients with acute coronary syndromes and after percutaneous coronary interventions (PCIs). In combination with aspirin, the ADP receptor antagonist clopidogrel is used widespread for this purpose; however, platelet reactivity after clopidogrel differs substantially between patients and high on-treatment platelet reactivity (HTPR) persists in a substantial proportion of cases. Since more than 20 prior observational studies linked HTPR to higher risk of ischemic events, including cardiovascular death, myocardial infarction, and stent thrombosis, monitoring post-clopidogrel platelet reactivity after PCI might be beneficial for risk assessment and to tailor the antiplatelet therapy to the patients' needs. However, there is no consensus on the role of routine platelet function monitoring in clinical guidelines. This article aims to review the available evidence regarding the clinical relevance of platelet function monitoring, highlighting possible reasons for the controversy between guidelines and observational studies.