阿司匹林联合双嘧达莫用于缺血性脑卒中二级预防的Meta分析

目的以阿司匹林为对照组,系统评价阿司匹林双嘧达莫联合用药,对缺血性脑卒中二级预防的有效性和安全性。方法通过卒中、非致死性卒中、各种原因引起的死亡及非致死性卒中与各种原因引起的死亡联合事件发生的相对危险度,分析联合用药的有效性,通过出血性并发症及脑出血发生的相对危险度,分析联合用药的安全性。结果 a.与阿司匹林相比较,联合用药能更有效的预防卒中的发生(RR=0.86 95%CI[0.74,1.00]),使非致死性卒中的发生率降低22%(RR=0.78 95%CI[0.67,0.90]),也能明显降低非致死性卒中与各种原因引起的死亡联合事件的发生率(RR=0.87 95%CI[0.79,0.96])。但是,联合用药对各种原因引起的死亡无效(RR=0.98,95%CI[0.85,1.13])。b.与阿司匹林相比较,联合用药不会增加出血性并发症的发生率(RR=0.95,95%CI[0.80,1.12]),但可以使脑出血的发生率增加14%(RR=1.14,95%CI[0.54,2.42]),尽管这一结果无明显统计学意义。结论与阿司匹林相比较,联合用药对卒中、非致死性卒中及非致死性卒中与各种原因引起的死亡联合事件的预防更有效,联合用药不会增加出血性并发症的发生率,但能轻微增加脑出血的发生率。     

Antiplatelet therapy in secondary stroke prevention

Stroke is the third leading cause of death in the United States. Antiplatelet agents are the mainstays of ischaemic stroke prevention. The therapies recommended for initial therapy include aspirin (50 - 325 mg) daily, the combination of aspirin (25 mg) and extended-release dipyridamole (200 mg) b.i.d., or clopidogrel (75 mg) daily. Ticlopidine 250 mg b.i.d. is approved for stroke prevention but is no longer a first-line therapy. This article reviews the literature on antiplatelet agents for secondary stroke prevention.     

Antiplatelet therapy as a modulator of stroke aetiology: a meta-analysis

Aims

Antiplatelet therapy reduces the incidence of ischaemic stroke. Platelet-mediated thrombosis contributes variably to the major subtypes of stroke as defined by the TOAST criteria: large artery atherosclerosis (LAA), cardioembolic (CE) and small vessel occlusion (SVO). The effect of antiplatelet therapy on the incidence of each subtype is unknown and is the subject of this meta-analysis.

Methods

Electronic databases were searched for articles comparing the effect of antiplatelet therapy on the incidence of stroke according to aetiological subtype. Studies containing subjects prescribed anticoagulant therapy or solely investigating subjects with atrial fibrillation were excluded. Pooled odds ratios (ORs) were calculated using a fixed effects model.

Results

Nine studies were included (n = 5739). In patients who had an ischaemic stroke, pre-event antiplatelet therapy was associated with significantly decreased incidence of LAA (OR 0.88, 95% CI 0.79, 0.99; P = 0.026), increased incidence of CE (OR 1.23, 95% CI 1.08, 1.41; P = 0.002) and no effect on SVO (OR 0.99, 95% CI 0.88, 1.11; P = 0.806). Concordant non-significant trends were observed in primary prevention populations (n = 751): LAA (OR 0.81, 95% CI 0.57, 1.15; P = 0.240), CE (OR 1.29, 95% CI 0.89, 1.87; P = 0.179) and SVO (OR 0.99, 95% CI 0.73, 1.36; P = 0.970). Subgroup analysis of aspirin monotherapy (n = 3786) demonstrated a significant reduction in LAA (OR 0.87, 95% CI 0.76, 1.00; P = 0.046), but non-significant effects on the incidence of CE (OR 1.17, 95% CI 0.99, 1.39; P = 0.068) and SVO (OR 1.04, 95% CI 0.91, 1.20; P = 0.570). Probability of publication bias was low (P > 0.05).

Conclusions

Antiplatelet therapy preferentially reduces the incidence of LAA stroke compared with CE and SVO subtypes.     

Antiplatelet Drug Resistance and Drug-Drug Interactions: Role of Cytochrome P450 3A4

Antiplatelet therapy provided pivotal advances in the treatment of cardiovascular disease. Aspirin and thienopyridine, clopidogrel, is currently the treatment of choice in acute coronary syndromes and the prevention of thrombosis after coronary stent implantation. Despite the efficacy of this dual antiplatelet therapy in reduction of adverse coronary events in patients with acute coronary syndromes, complications persist in a subgroup of these patients. Emerging causes of aspirin and clopidogrel resistance may translate to increase risk for recurrent myocardial infarction, stroke, or cardiac related mortality. However, the mechanism of antiplatelet drug resistance remains incompletely characterized, and a sensitive and specific assay of aspirin and clopidogrel effect that reliably predicts treatment failure has not emerged. To date, evidence supporting antiplatelet drug resistance are pharmacokinetic response variability, drug-drug interaction through competitive inhibition a specific enzymatic pathway, genetic variability, and variability in the induction of enzymatic pathway in metabolic activation of prodrugs, like clopidogrel. Further investigation or guidelines are needed to optimize antiplatelet treatment strategies to identify and treat patients resistant to aspirin and/or clopidogrel.     

P2Y12 receptor inhibitors for secondary prevention of ischemic stroke

Introduction: Ischemic stroke (IS) is a major cause of death and disability worldwide. The P2Y₁₂ receptor plays a critical role in the formation of a stable thrombus leading to ischemic complications. Therefore, P2Y₁₂ receptor inhibitors constitute a major antiplatelet strategy in the secondary prevention of IS.

Areas covered: We searched articles about P2Y₁₂ receptor inhibitors and stroke in PubMed published until December 2014. This is a comprehensive review of the role of P2Y₁₂ receptor inhibitors alone and in combination with aspirin in the secondary prevention of noncardioembolic stroke.

Expert opinion: The potential benefit of more potent antiplatelet therapy for secondary stroke prevention must be weighed against the risk of bleeding in patients with IS. Short-term (≤ 3 months) dual antiplatelet therapy with clopidogrel and aspirin that is initiated early after IS or transient ischemic attack due to large artery atherosclerosis appears most efficient.     

Antiplatelet therapy in acute coronary syndromes

Introduction: Coronary thrombosis is a frequent cause of death and myocardial infarction most often explained by superimposition of a platelet-rich thrombus on existing coronary artery disease. Therefore, antiplatelet drugs are essential in the treatment and secondary prevention of acute coronary syndromes (ACS) and during percutaneous coronary intervention. Several novel antiplatelet drugs are now available.

Areas covered: For several years, aspirin and clopidogrel remained the cornerstone of treatment for ACS. However, prasugrel and ticagrelor have a more consistent, faster-acting and more potent antiplatelet effect than clopidogrel, which translates into improved clinical outcomes, although at the expense of an increased bleeding risk. Importantly, some patients experience cardiovascular events despite current antiplatelet treatment, because platelet activation may occur via pathways not inhibited by these agents. Therefore, improved antiplatelet strategies are warranted.

Expert opinion: Despite undisputable benefits of current antiplatelet strategies, a considerable number of patients continue to experience adverse thrombotic events, although clinical outcomes have been improved with new oral P2Y₁₂ antagonists. New drugs have been developed, including intravenous P2Y₁₂ antagonists and oral antagonist targeting the protease-activated receptor-1 platelet activation pathway stimulated by thrombin. This review provides an overview of current and novel antiplatelet strategies and also discusses unmet needs related to antiplatelet therapy for ACS.     

抗血小板药物致胃肠道出血的防治进展

抗血小板聚集是血栓栓塞性疾病防治的重要措施,但由抗血小板药物引发的胃肠道损害临床常见。本文就阿司匹林与氯吡格雷等抗血小板药物导致胃肠道出血的研究现状及其防治的研究进展作一综述。     

Non-vitamin-K oral anticoagulants (NOACs) for the prevention of secondary stroke

ABSTRACT

Introduction: In patients with atrial fibrillation (AF), oral anticoagulation with vitamin K antagonists (VKA) (warfarin, phenprocoumon) is effective both for primary and secondary stroke prevention with a 60–70% relative reduction in stroke risk compared with placebo. Mortality is reduced by 26%. VKA have a number of well-documented shortcomings which were overcome by non-vitamin-K oral anticoagulants (NOACs).

Areas covered: Results of randomized trials for four NOACs (apixaban, dabigatran, edoxaban, rivaroxaban) have been published (ARISTOTLE, RE-LY, ENGAGE, ROCKET-AF). In this review, the authors discuss the results in subgroups of patients with prior transient ischemic attacks or ischemic stroke. In aggregate, the NOACs are superior to warfarin for secondary prevention and result in a 50% reduction in intracerebral hemorrhage. Apixaban was superior to aspirin in the AVERROES trial and had a similar rate of major bleeding complications.

Expert opinion: NOACs add to the therapeutic options for secondary stroke prevention in patients with AF and offer advantages over warfarin including a favorable bleeding profile and convenience of use. Aspirin should no longer be used for secondary stroke prevention in patients with AF.     

Design,Synthesis and Pharmacological Evaluation of Novel Piperlongumine derivatives as Potential Antiplatelet Aggregation Candidate

A series of novel piperlongumine derivatives ( 4a‐i , 6a‐i ) were designed and synthesized. The inhibitory activities of platelet aggregation induced by ADP and AA in vitro have been evaluated by bron turbidimetry and liver microsomal incubated assay. The assay results show that compounds 4e and 6e exhibited remarkable potency to that of the positive control piplartine and aspirin.     

瑞舒伐他汀用于缺血性脑卒中二级预防的疗效及安全性观察

目的:研究瑞舒伐他汀用于缺血性脑卒中二级预防的疗效及安全性。方法:选择我院90例缺血性脑卒中合并高脂血症患者,随机分为瑞舒伐他汀组、辛伐他汀组和饮食控制组,每组30例,瑞舒伐他汀组患者于每晚餐后顿服瑞舒伐他汀钙片10 mg,辛伐他汀组于每晚餐后顿服辛伐他汀片40 mg,饮食控制组采用饮食控制手段,不服用他汀类降脂药物,疗程均为12周。12周后观察3组患者的降脂疗效及安全性。结果:各组患者TC、TG和LDL-C水平均明显降低,但瑞舒伐他汀组的TC、TG、LDL-C水平降低较其他2组明显(P<0.05),3组疗效比较差异有统计学意义(P<0.05)。瑞舒伐他汀钙10 mg组的胆固醇达标率优于辛伐他汀组和饮食控制组,组间差异有统计学意义(χ2=7.937,P<0.05)。结论:瑞舒伐他汀钙用于缺血性脑卒中的二级预防疗效显著,且安全性好,值得临床推广。     

抗血小板治疗在缺血性脑卒中预防中的应用

抗血小板治疗是缺血性脑卒中(IS)一级和二级预防的重要组成部分,未接受溶栓治疗的急性IS患者应尽早开始阿司匹林治疗.噻吩吡啶类药物及血小板糖蛋白Ⅱ b/Ⅲ a受体抑制剂等单药用于急性IS治疗的安全性和有效性目前尚缺乏足够证据,抗血小板药物联合应用的疗效和可能的风险尚需进一步研究.对无法采用华法林治疗的高危房颤患者,阿司匹林或阿司匹林+氯吡格雷双联治疗是当前比较推崇的补充选择手段.     

血栓弹力图指导抗血小板治疗对缺血性脑卒中二级预防效果影响的研究

目的分析血栓弹力图(TEG)指导抗血小板治疗在急性缺血性脑卒中(CIS)二级预防中的应用效果。方法86例CIS患者,随机分为TEG组与常规组,每组43例。常规组接受常规抗血小板治疗,TEG组接受TEG指导下抗血小板治疗。比较两组抗血小板药物抵抗发生率、血小板计数(PLT)、花生四烯酸诱导的血小板抑制率(AA%)及二磷酸腺苷诱导的血小板抑制率(ADP%)水平变化,分析CYP2C19基因型与ADP%水平的相关性。结果治疗7 d后,两组阿司匹林抵抗及氯吡格雷抵抗发生率比较,差异无统计学意义(P>0.05)。治疗前、治疗7 d后、治疗14 d后,两组PLT水平均呈降低趋势,差异有统计学意义(P<0.05)。常规组AA%水平呈降低趋势,TEG组AA%水平呈先降低后升高趋势,差异有统计学意义(P<0.05)。常规组ADP%水平呈降低趋势,TEG组ADP%水平呈先降低后升高趋势,差异有统计学意义(P<0.05)。治疗14 d后,TEG组PLT水平(228.28±17.16)×10^9/L低于常规组的(237.31±18.52)×10^9/L,差异有统计学意义(P<0.05)。TEG组AA%水平高于常规组,差异有统计学意义(P<0.05)。TEG组ADP%水平高于常规组,差异有统计学意义(P<0.05)。经Pearson相关性分析显示,CYP2C19基因型代谢程度与ADP%水平呈正相关(r=0.692,P<0.05)。结论在CIS二级预防中TEG指导下应用抗血小板药物可有效的改善血小板药物抵抗,提高抗血小板治疗效果。     

PCI术后抗血小板联合抗凝治疗患者消化道出血危险因素及治疗策略分析

目的 分析抗血小板及抗凝药物致消化道出血的危险因素及治疗策略。方法 临床药师参与1例消化道出血患者的治疗过程,从具体案例着手,结合患者病情进行系统分析。结果 双联抗血小板、华法林、未系统监测INR、高龄、未预防性使用质子泵抑制剂等引起患者慢性消化道出血加重,通过对症止血、补血处理及停用抗血小板及抗凝药物,患者出血症状得到有效控制。结论 对于消化道出血高危人群,应及时加用质子泵抑制剂至少3个月预防治疗。新型胃黏膜保护剂如瑞巴匹特等对抗血小板药物导致的消化道损伤亦有显著的预防作用,可考虑作为质子泵抑制剂的替代治疗。     

Antiplatelet therapy in acute coronary syndromes

Introduction: Antiplatelet therapy is the cornerstone of treatment for patients with acute coronary syndromes in the acute phase and in long-term management. Over the last few years, new antiplatelet drugs have been developed and the therapeutic landscape has rapidly evolved.

Areas covered: We review the available evidence and most recent data concerning all of the principal classes of antiplatelet agents, including aspirin, thienopyridines and glycoprotein IIb/IIIa inhibitors, as well the impact of the new drugs prasugrel and ticagrelor and the available data concerning cangrelor, elinogrel and PAR-1 inhibitors (still under development).

Expert opinion: This review considers the management of antiplatelet therapy in the light of recent advances, highlighting how to identify patients who will receive the greatest benefit from the older and newer agents, and underscoring the importance of carefully balancing the risks of ischaemia and bleeding in order to improve clinical outcomes. Finally, the paper discusses the potential role of functional and genetic tests in guiding the choice of antiplatelet therapy in a future perspective of ‘personalised medicine’.     

抗血小板药物的合理应用(一)

心、脑血管疾病是导致人类死亡的主要病因,动脉粥样硬化血栓形成是心、脑血管疾病的病理基础,其中血小板激活和聚集在其形成过程中起核心作用。抗血小板治疗有助于减少心、脑血管不良事件的发生。根据循证医学的要求,重点介绍目前临床应用较多的5类抗血小板药物中的4个代表性药物,包括其适应证、用法用量、注意事项和联合用药等。     

抗血小板药物的合理应用(二)

心、脑血管疾病是导致人类死亡的主要病因,动脉粥样硬化血栓形成是心、脑血管疾病的病理基础,其中血小板激活和聚集在其形成过程中起核心作用。抗血小板治疗有助于减少心、脑血管不良事件的发生。根据循证医学的要求,重点介绍目前临床应用较多的5类抗血小板药物中的4个代表性药物,包括其适应证、用法用量、注意事项和联合用药等。     

高龄急性冠脉综合征患者双联抗血小板治疗的疗效及安全性探讨

目前,双联抗血小板治疗(dual antiplatelet therapy,DAPT)仍然是急性冠脉综合征(ACS)的一线治疗方法。强化抗血小板治疗带来心血管获益的同时,由此引起的出血风险的增加也值得关注。文中通过回顾近些年来国内外几项大型临床试验,综述得出:高龄ACS患者给予DAPT有效且相对安全;对于有出血危险因素及需要长期应用阿司匹林(尤其是接受DAPT)者,可选择较低剂量阿司匹林(75～81 mg.d-1);年龄>75岁者,不推荐给予氯吡格雷负荷剂量(300 mg);服用阿司匹林和(或)氯吡格雷时,不推荐常规应用质子泵抑制剂预防胃肠道不良反应。     

灯盏生脉胶囊用于缺血性脑卒中二级预防的成本效用分析

目的:对于中国缺血性脑卒中患者,分析使用灯盏生脉胶囊联合标准二级预防方案或单用标准预防方案进行二级预防的成本效用.方法:基于全社会视角,构建Markov模型,模拟患者5年的成本和质量调整生命年.模型包括4个健康状态,分别是未复发卒中、复发卒中不依赖他人照料(mRSO-2)、复发卒中依赖他人照料(mRS3-5)和死亡.临...