抗血小板药物治疗的实验室检测

基于一级和二级预防实验结果,当前国内外的缺血性心脑血管疾病防治指南均推荐应用抗血小板药物（Ⅰ级证据）。但值得注意的是约一半患者对抗血小板药物存在＂抵抗＂或＂无效＂的认识,针对上述患者的临床发现存在滞后性。本文重点讨论一些当前国内外用于抗血小板药物（阿司匹林和氯吡格雷）疗效评价实验室方法的优缺点。一些方法已应用于基础和临床研究且有证据支持可预测抗血小板药物的疗效。但至今尚无任何一项研究是通过上述实验室方法检测抗血小板药物来说明改变治疗的临床转归。因此未来的发展应是寻找更加有药物特异性和非特异性的实验室方法,并探讨这些实验室指标与药物临床效果的量化联系。     

抗血小板药物抵抗与复发性缺血性脑卒中

缺血性脑卒中在抗血小板治疗期间1/3~1/2的患者卒中复发。卒中复发有多种原因,多认为病人的不依从性是实验室抗血小板药物抵抗的最常见原因,但需要正确识别卒中的原因和发病机制。目前还没有良好指征用于缺血性卒中抗血小板药物抵抗的检测,或根据检测结果调整药物剂量的方法。选择预防卒中复发的抗血小板药物取决于卒中发作的时间,轻度缺血性卒中在发病3个月内选用阿司匹林联合氯吡格雷优于单一的抗血小板药物,但对长期二级预防来说,联合应用抗血小板治疗不仅无益处,且有增加出血的风险。     

缺血性脑卒中二级预防中的抗血小板治疗及其研究进展

抗血小板治疗是缺血性脑卒中二级预防中影响脑卒中再发率的重要因素。阿司匹林和氯吡格雷是临床常用的抗血小板药物。缺血性脑卒中二级预防中抗血小板药物的联合应用以及新药的研究已成为时下热点。由于缺血性脑卒中发病后早期再发率较高,因此早期以及长期二级预防中的抗血小板治疗方式不尽相同。     

阿司匹林和氯吡格雷抗血小板抵抗机制及临床治疗研究进展

脑梗死的发病率和致死率极高,其病因主要是动脉粥样硬化性脑血栓形成,抗血小板治疗是动脉粥样硬化性脑梗死急性期及二级预防的重要环节。阿司匹林和氯吡格雷是目前在临床应用最为广泛的抗血小板药物,但是抗血小板聚集作用在不同个体间存在较大差异,部分人群对于抗血小板药物的反应性较低,称为抗血小板药物抵抗。文中阐述了导致阿司匹林和氯吡格雷抵抗的主要机制以及临床上针对此种现象所采取的治疗措施,旨在为脑梗死患者的个性化治疗提供参考。     

抗血小板药预防脑卒中的应用进展

以阿司匹林为代表的抗血小板药已被证实在对脑卒中预防有确实的疗效。阿司匹林、氯吡格雷等抗血小板药物作为脑卒中预防的基础用药,其疗效确切并已经列入相关脑卒中预防指南。替卡格雷、西洛他唑、三氟柳、沙格雷酯等新型抗血小板药物在部分地区的临床试验中也已经取得了令人满意的脑卒中预防结果。但是多年来,阿司匹林的最佳预防剂量仍在商榷中,在患者应用抗血小板药物的过程中,存在一定比例的出血并发症。当两种抗血小板药物合用更可能导致出血并发症的发生比例增高。寻求抗血小板药的疗效及出血并发症间的平衡点,促进抗血小板药物的进步与发展。文中就抗血小板药物在预防脑卒中的应用进展作介绍。     

抗凝、抗血小板治疗相关的颅内出血

本文在简要介绍主要抗凝和抗血小板药物的基础上,总结了抗凝和抗血小板相关颅内出血的发生率、死亡率和危险因素。主要危险因素是高龄、血压高、抗凝治疗剂量与时间和既往有脑缺血病史。联合应用抗凝和抗血小板药物及合用不同抗血小板药物可增加颅内出血发生率。维持抗凝时INR≤3.0、控制血压、避免联合应用抗凝和抗血小板药物可减少颅内出血发生率。     

抗血小板治疗在血管内治疗缺血性脑血管病中的应用

血管内治疗能显著降低缺血性脑血管病的致残、病死及卒中复发率。随着神经介入技术 和材料以及患者筛选策略的进步，缺血性卒中患者应用血管内治疗也日益增加。抗血小板治疗作为 缺血性卒中预防和治疗的重要手段，是血管内治疗中的重要一环，阿司匹林、氯吡格雷等是基石性 抗血小板药物，但具体的用药方案尚不统一。本文回顾和总结了国内外指南针对缺血性脑血管病行 血管内治疗患者的抗血小板策略建议，以及重要血管内治疗研究中采用的抗血小板治疗方案，以期 为神经介入医师行血管内治疗时抗血小板药物的应用提供参考。     

新型抗血小板药物对缺血性卒中的防治作用

抗血小板药物目前仍是缺血性卒中急性期治疗和二级预防的常规用药。经典抗血小板药物阿司匹林、氯吡格雷的临床疗效已经肯定,但仍存在一些不足,如药物耐受性、增加出血风险等。因此,新型抗血小板药物以其不同的药代动力学和药效学特性与经典抗血小板药物互补,并能克服其临床应用的局限性而受到关注并逐渐在临床推广应用。本文拟对已发表的新型抗血小板药物的临床研究证据进行概述,并提出其临床应用所面临的挑战。     

基因多态性与抗血小板药物个体化治疗研究

血小板的活化与聚集在血栓形成的病理生理中起着重要的作用,而抗血小板治疗是动 脉硬化性脑梗死急性期治疗、一级及二级预防的重要组成部分。目前阿司匹林、氯吡格雷为最常用 的抗血小板药物。但抗血小板药物对不同人群血小板抑制作用存在较大差异,人群对抗血小板药 物的低反应性与缺血性脑血管病复发具有相关性,本篇将重点从基因多态性的角度阐述抗血小板 药物抵抗的可能机制,指导临床个体化治疗。     

408例缺血性脑血管病二级预防抗血小板药物应用状况调查

目的 了解北京市部分二级医院缺血性脑血管病二级预防抗血小板药物的应用现状,为改进缺血性脑血管病二级预防工作提供依据.方法 本研究为现况调查,研究对象为以自愿形式参加的北京市4家二级医院中急性脑梗死及短暂性脑缺血发作(TIA)的住院患者,调查其住院期间以及出院3个月二级预防抗血小板药物的应用现况.结果 人选患者共458例.其中408例完成3个月随访.住院期间抗血小板药物应用率为93.7%,3个月随访发现.抗血小板药物的院外治疗依从性差,应用率明显下降,为69.6%(P=0.003);男性(OR=1.708),95%CI 1.083～2.691及TIA患者(OR=1.954,95%CI1.046～3.649)成为患者抗血小板药物依从性差的促进因素.结论 北京市部分二级医院缺血性脑血管病二级预防抗血小板药物的应用现状不容乐观,临床医生应对缺血性脑血管病患者二级预防抗血小板药物的依从性给予关注.     

抗血小板药物治疗腔隙性梗死效果的Meta分析

目的评价抗血小板药物对腔隙性梗死患者二级预防的治疗效果。方法以stroke,lacunar infarction,platelet aggregation inhibitors,antiplatelet,randomized controlled trial等英文词汇计算机检索1980年1月1日-2016年11月20日美国国立医学图书馆生物医学信息检索系统、荷兰医学文摘、Cochrane在线图书馆等数据库收录的关于腔隙性梗死患者抗血小板治疗的随机对照临床试验,采用Jadad量表、Cochrane系统评价手册和Rev Man 5.3统计软件进行文献质量评价和Meta分析,R软件Gemtc程序包和JAGS软件进行网状Meta分析。结果共获得4068篇英文文献,经剔除重复和不符合纳入标准者,最终纳入12项质量较高(Jadad评分≥4分)的临床试验共24 969例腔隙性梗死患者。Meta分析显示:与安慰剂相比,抗血小板药物单抗治疗可以显著降低缺血性卒中复发率(RR=0.480,95%CI:0.300~0.780;P=0.003)和所有脑卒中复发率(RR=0.780,95%CI:0.630~0.970;P=0.030);而抗血小板药物单抗与双抗治疗效果差异无统计学意义(缺血性卒中复发率:RR=0.900,95%CI:0.760~1.050,P=0.170;所有脑卒中复发率:RR=0.910,95%CI:0.820~1.010,P=0.070)。网状Meta分析(包括阿司匹林、安慰剂、西洛他唑和噻氯匹定4种干预措施)显示:仅西洛他唑治疗后所有脑卒中复发率低于阿司匹林(OR=0.341,95%Cr I:0.011~0.673)和安慰剂(OR=0.615,95%Cr I:0.191~1.042)。结论抗血小板药物单抗治疗可以显著降低腔隙性梗死患者缺血性卒中和所有脑卒中复发风险,且与双抗治疗效果无明显差异;西洛他唑较阿司匹林能够更显著降低腔隙性梗死患者所有脑卒中复发风险。     

Carotid artery stenting: Current state of evidence and future directions

Both carotid endarterectomy (CEA) and carotid artery stenting (CAS) are common treatments for carotid artery stenosis. Several randomized controlled trials (RCTs) have compared CEA to CAS in the treatment of carotid artery stenosis. These studies have suggested that CAS is more strongly associated with periprocedural stroke; however, CEA is more strongly associated with myocardial infarction. Published long‐term outcomes report that CAS and CEA are similar. A reduction in complications associated with CAS has also been demonstrated over time. The symptomatic status of the patient and history of previous CEA or cervical radiotherapy are significant factors when deciding between CEA or CAS. Numerous carotid artery stents are available, varying in material, shape and design but with minimal evidence comparing stent types. The role of cerebral protection devices is unclear. Dual antiplatelet therapy is typically prescribed to prevent in‐stent thrombosis, and however, evidence comparing periprocedural and postprocedural antiplatelet therapy is scarce, resulting in inconsistent guidelines. Several RCTs are underway that will aim to clarify some of these uncertainties. In this review, we summarize the development of varying techniques of CAS and studies comparing CAS to CEA as treatment options for carotid artery stenosis.     

Network meta-analysis of prasugrel, ticagrelor, high- and standard-dose clopidogrel in patients scheduled for percutaneous coronary interventions

Since novel antiplatelet treatments (prasugrel, ticagrelor, high-dose clopidogrel) have been predominantly tested against standard-dose clopidogrel, data on direct comparisons between these therapies are scarce. We therefore indirectly compared their efficacy and safety in patients undergoing percutaneous coronary intervention. Electronic databases were searched systematically to identify head-to-head randomised controlled trials (RCTs). Network meta-analysis was performed using generalised linear mixed models with adjustment for length of follow-up. Findings were corroborated by mixed treatment comparison through Bayesian methods. Fourteen RCTs were identified and included in the analysis (high- vs. standard-dose clopidogrel: 9 trials, prasugrel vs. high-dose clopidogrel: 2 trials, prasugrel vs. standard-dose clopidogrel: 2 trials, ticagrelor vs. standard-dose clopidogrel: 1 trial). No significant differences were found for efficacy outcomes except for stent thrombosis favouring prasugrel (vs. ticagrelor: odds ratio [OR] 0.63, 95% confidence interval [CI]: 0.42, 0.94; vs. high-dose clopidogrel: OR 0.70, 95%CI: 0.48, 1.01). Prasugrel exhibited a similar bleeding risk as high-dose clopidogrel, but more major (OR 1.43, 95%CI 1.07, 1.90) and major or minor bleeding (OR 1.36, 95%CI 1.09, 1.69) compared to ticagrelor. Ticagrelor was also associated with less major or minor bleeding compared to high-dose clopidogrel (OR 0.81, 95%CI 0.69, 0.96). No differences were seen for non CABG-related major bleeding between the three strategies. Results were corroborated in a subgroup analysis comprising only patients with acute coronary syndromes. In the absence of head-to-head clinical trials, network meta-analysis suggests potentially relevant differences in efficacy and bleeding risk among novel antiplatelet treatments and may thereby advance understanding of their differential therapeutic properties.     

IV Valproate in generalized convulsive status epilepticus: a systematic review

Aim of this review was to evaluate efficacy and safety of intravenous valproate (IV VPA) in the treatment of generalized convulsive status epilepticus (GCSE) in patients of any age, synthesizing available evidences from randomized controlled trials (RCTs). RCTs on IV VPA administered in patients (no age restriction) for GCSE at any stage were searched in MEDLINE, EMBASE and Cochrane Central Register of Controlled Trials. Studies were selected and data independently extracted. Following outcomes were considered: clinical seizure cessation after drug administration, seizure freedom at 24 h, and adverse effects. Outcomes were assessed using standard methods to calculate risk ratio (RR) with 95% confidence intervals. Five trials met inclusion criteria. Two different comparisons were available (IV VPA versus phenytoin (PHT), IV VPA versus IV Diazepam), but only the former included more than one study with enough information to permit a meta-analysis. Compared with PHT, VPA had statistically lower risk of adverse effects (RR 0.31, 95% CI 0.12-0.85), with no differences in GCSE cessation after drug administration (RR 1.31, 95% CI 0.93-1.84) and in seizure freedom at 24 h (RR 0.96, 95% CI 0.88-1.06). This review suggests that IV VPA has a better tolerability than PHT in treatment of GCSE, without any statistically significant differences in terms of efficacy. More rigorous RCTs of VPA versus an appropriate comparator, in a well-defined population with a systematic definition of SE, are however required to conclude about efficacy and tolerability of VPA in clinical practice.     

Efficacy and acceptability of atypical antipsychotics for the treatment of post-traumatic stress disorder: A meta-analysis of randomized,double-blind,placebo-controlled clinical trials

As some evidences demonstrated that atypical antipsychotics (AA) may be efficacious in treating post-traumatic stress disorder (PTSD), we preformed a meta-analysis of randomized, double-blind, placebo-controlled clinical trials (RCTs) of AAs for the treatment of PTSD. Two hundred and fifty one papers were searched and screened. Eight RCTs met the inclusion criteria. AAs may be superior to placebo in the treatment of PTSD, as indicated by the changes in Clinician Administered PTSD Scale (CAPS) total scores (weighted mean differences (WMD)=−5.89, 95% confidence interval (CI) [−9.21, −2.56], P=0.0005) and also in CAPS subscale intrusion (WMD=−2.58, 95% CI[−3.83, −1.33], P<0.0001 ) and subscale hyperarousal (WMD=−2.94, 95% CI[−5.45, −0.43], P=0.02). The acceptability measured by dropout rates between AAs and placebo showed no statistical difference (OR=1.24, 95%CI [0.78, 1.97], P=0.36). PTSD symptom cluster, especially in intrusion and hyperarousal. However, we should be careful to generalize the conclusion because of the small number of included trails. We expect more RCTs will be done in the future so as to clarify the specific value of AAs for PTSD.     

Antiplatelet therapy and future intracerebral hemorrhage in hemodialysis patients with cerebral microbleeds

The use of antiplatelet drugs is thought to increase the risk for intracerebral hemorrhage (ICH) in patients with cerebral microbleeds (CMBs). However, hemodialysis (HD) patients have a high prevalence of CMBs and diverse pathologies that require antiplatelet therapy. In this study, we investigated whether the use of antiplatelet drugs increases the risk for ICH in HD patients with CMBs. Brain magnetic resonance imaging (MRI), including T2*-weighted MRI, was performed in 179 HD patients with no history of cerebrovascular events. CMBs were detected and patients were followed prospectively with a median follow-up period of 5.2 [1.4–6.2] years. To investigate whether the influence of antiplatelet therapy on the development of ICH differs in cases with and without CMBs, the inverse probability of treatment weighting method was used, including an interaction term between the presence or absence of CMBs and use of antiplatelet drugs. As a result, CMBs were detected in 45 patients (25.1%), and antiplatelet drugs were used in 66 patients (36.9%). When the effect of antiplatelet therapy on the incidence of ICH was modified by the presence of CMBs at baseline (P for interaction <0.001), the use of antiplatelet drugs was a significant risk factor for ICH in HD patients without CMBs, but not in HD patients with CMBs. Furthermore, the burden of CMBs significantly increased the risk for ICH, but the increase in this risk was slower in antiplatelet drug users as compared to non-antiplatelet drug users (P for interaction = 0.02). The influence of antiplatelet drugs on the development of ICH differed depending on the presence or absence of CMBs. In fact, the use of antiplatelet drugs did not increase the risk for ICH in HD patients with CMBs.     

Antiplatelet resistance in stroke

Although the exact prevalence of antiplatelet resistance in ischemic stroke is not known, estimates about the two most widely used antiplatelet agents - aspirin and clopidogrel - suggest that the resistance rate is high, irrespective of the definition used and parameters measured. Inadequate antiplatelet responsiveness correlates with an increased risk of recurrent ischemic vascular events in patients with stroke and acute coronary syndrome. It is not currently known whether tailoring antiplatelet therapy based on platelet function test results translates into a more effective strategy to prevent secondary vascular events after stroke. Large-scale clinical trials using a universally accepted definition and standardized measurement techniques for antiplatelet resistance are needed to demonstrate whether a 'platelet-function test-guided antiplatelet treatment' strategy translates into improved stroke care. This article gives an overview of the clinical importance of laboratory antiplatelet resistance, describes the challenges for platelet-function test-guided antiplatelet treatment and discusses practical issues about the management of patients with aspirin and/or clopidogrel resistance.     

Handling clinical comorbidity in randomized clinical trials in psychiatry

The purpose of this paper is to a) outline the importance of including patients with clinical comorbidities in Randomized Clinical Trials (RCTs) of psychiatric treatments; and b) to propose a specific approach for best handling, analyzing and interpreting the data on clinical comorbidities in terms of their impact on treatment outcomes. To do this we first define and describe clinical comorbidity and differentiate it from other forms of comorbidity. We then describe the methodological and analytical problems associated with excluding patients with clinically comorbid conditions from RCTs, including the impact on the outcomes of RCTs in psychiatry and the impact on evidence-based clinical decision-making. We then address the challenges inherent to including patients with clinical comorbidities in RCTs. Finally, we propose a methodological and analytic approach to deal with these issues in RCTs which aims to significantly improve the information yielded from RCTs in psychiatry, and thus improve clinical decision-making.     

Antiplatelet therapies and the role of antiplatelet resistance in acute coronary syndrome

Acute coronary syndrome is the number one killer in the industrialized world and, as such, continues to be one of the most well-studied disease states in all of medicine. Advancements in antiplatelet therapies for use in patients undergoing percutaneous coronary intervention have improved outcomes dramatically. However, a proportion of patients on long-term antiplatelet therapy continue to have cardiovascular events. Resistance to antiplatelet drugs may explain some of these events and this topic has become one of major interest and rapid evolution. This review describes the pathogenesis of acute coronary syndromes, outlines the evidence behind the use of the available antiplatelet agents, and examines the current data surrounding antiplatelet resistance.