非心源性缺血性脑卒中二级预防中抗栓治疗的进展

<正>脑卒中是重要的死亡和残疾病因,除各种不良生活方式和血管性危险因素外,脑卒中和短暂性脑缺血发作(TIA)史本身就是重要复发危险因素,尤其是近期发生者。因此,为预防非心源性缺血性脑卒中或TIA的复发,抗血小板治疗(APT)是一个重要的预防措施。自2014年美国卒中学会及我国的相关缺血性脑卒中二级预防指南发表,针对非心源性缺血性脑卒中开展了几项重要的随机对照试验(RCT)和一些系统分析~([1-2])。本研究就此予以介绍。1双联抗血小板治疗(DAPT)我国开展的CHANCE试验证明,对高危轻型     

北京地区缺血性脑卒中或短暂性脑缺血发作二级预防的研究

目的对入院的缺血性脑卒中或短暂性脑缺血发作(TIA)患者采取ABCDE策略治疗,分析患者出院后能否维持高水平药物治疗的符合率。方法选择2007年8～12月连续收入北京地区21家医院神经内科病房的缺血性脑卒中和(或)TIA患者1166例,记录患者二级预防中抗血小板、降压、降糖及调脂药物等治疗情况,出院后对患者进行随访,分析出院后90d、6个月和1年二级预防中抗血小板、降压、降糖和调脂治疗的符合率。结果 1166例患者中,复发性脑卒中541例,其抗血小板治疗比例为58.4%,降压、降糖和他汀类药物治疗比例分别为82.3%、85.3%和14.2%。出院后,完成90d、6个月及1年随访的患者分别为1012例、1012例和981例,其二级预防中抗血小板、降压、降糖和调脂治疗的符合率维持在较高水平。结论复发性脑卒中二级预防现状不容乐观,采取ABCDE策略治疗,对入院的缺血性脑卒中或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的差距,患者出院后,二级预防治疗的符合率维持在较高水平。     

氯吡格雷在短暂性脑缺血发作后脑卒中二级预防中的应用

目的探讨氯吡格雷在短暂性脑缺血发作(transient ischemic attack,TIA)后预防缺血性脑卒中发作的疗效。方法选择TIA患者279例,随机分为2组:氯吡格雷组158例(氯吡格雷75 mg,1次/d),长效阿司匹林组121例(拜阿司匹林100 mg,1次/d)。患者随访1.5～3.0(2.3±0.3)年,评估2组的安全性。结果氯吡格雷组患者缺血性脑卒中复发率明显低于长效阿司匹林组,差异有统计学意义(5.06% vs 12.40%,P0.05)。全部患者在TIA后缺血性脑卒中复发的危险比为0.4031,氯吡格雷组为0.1284,长效阿司匹林组为0.8129,差异有统计学意义(P0.05)。氯吡格雷组患者发生次要事件概率和胃肠道出血事件明显低于长效阿司匹林组,差异有统计学意义(1.90% vs 8.26%,1.27% vs 6.61%,P0.05)。结论氯吡格雷对TIA患者的缺血性脑卒中的预防,优于长效阿司匹林。     

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。     

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。     

缺血性脑卒中急性期抗血小板治疗

脑卒中的高病死率和高致残率是对神经科临床的巨大挑战,进一步规范缺血性脑卒中急性期的各项诊治措施,是神经科大夫面临的一个重要课题.2007年AHA/美国卒中协会(ASA)更新了2005年版缺血性脑卒中急性期治疗指南,从循证医学的角度对缺血性脑卒中急性期治疗进行了总结.     

缺血性脑卒中伴高血压患者血压控制状况调查

目的了解缺血性脑卒中患者血压控制及降血压药物使用情况,分析影响降压药物使用的因素。方法选择2014年1~12月连续收住我院神经内科病房的住院且确诊为缺血性脑卒中和短暂性脑缺血发作患者总计740例,将360例复发性脑卒中纳入分析,高血压314例(87.2%),糖尿病142例,对入选患者血压控制及降血压药物使用情况进行调查。结果 314例高血压患者中,血压达标率为28.3%;142例糖尿病患者中,血压达标率为9.2%。314例高血压患者,服用任1种抗高血压药物248例,药物治疗率79.0%,有21.0%未服用任何降压药物。2型糖尿病、冠心病、吸烟、饮酒、服用抗血小板药物与降压药物治疗有关(P0.05)。冠心病(OR=0.275,95%CI:0.094~0.804,P=0.018)及服用抗血小板药物(OR=0.547,95%CI:0.310~0.966,P=0.038)是影响患者降压治疗的独立危险因素。结论缺血性脑卒中患者血压控制达标率与指南要求存在差距,伴糖尿病患者血压控制达标率更不理想,应加强脑卒中患者血压控制。     

缺血性脑卒中患者二级预防中抗血栓药物使用现况调查

目的调查缺血性脑卒中患者二级预防中抗血栓药物的使用情况,并分析其影响因素。方法本研究为现况调查,其对象为在北京天坛医院神经内科门诊就诊既往诊断明确的脑梗死或短暂性脑缺血发作患者(发病后4周~5年),调查其近两周内的抗血栓药物使用情况及相关影响因素。依据患者是否使用抗血栓药物,将入选患者分为两组:即治疗组与未治疗组。结果符合入选标准的缺血性脑卒中患者共计669例,最后共有607例缺血性脑卒中患者进入本研究结果分析中。其中未接受抗血栓药物治疗者163例(26.9%)。使用阿司匹林的患者中438例,其中剂量25~40 mg/d的患者152例(34.7%)。在抗血栓药物的影响因素方面,较好的日常生活能力OR=1.009,95%CI:1.002~1.017、医疗保险OR=1.822,95%CI:1.123~2.956、高血压OR=1.533,95%CI:1.030~2.282是脑卒中患者接受药物治疗的促进因素。结论缺血性脑卒中幸存者均应给予抗血小板药物或抗凝药物,除非预计患者不久将死亡或有严重的禁忌证,其用药剂量应遵循临床指南。     

缺血性脑卒中二级预防他汀类药物应用状况调查

目的了解缺血性脑卒中患者他汀类药物使用情况,分析影响他汀类药物使用的因素。方法从2014年1~12月连续收住我院神经内科住院的740例缺血性脑卒中患者中,选择360例复发性脑卒中患者,根据患者是否应用他汀类药物分为治疗组131例,未治疗组229例。按LDL-C2.6mmol/L的标准为治疗达标,调查340例患者入院时他汀类药物应用情况,并对相关的危险因素进行logistic回归分析。结果 360例患者中,服用他汀类药物131例,药物治疗率36.4%,未用他汀类药物229例,占63.6%。治疗组与未治疗组年龄≥65岁(58.8%vs47.2%)、高脂血症(30.5%vs 19.2%)、冠心病(32.1%vs 8.3%)和2型糖尿病(55.7%vs 30.1%)比较,差异有统计学意义(P0.05,P0.01)。未服用他汀类药物的原因中,患者自行停药及病情好转停药63.3%,医师未建议服用22.7%,存在药物不良反应5.2%。LDL-C达标患者104例,达标率为28.9%。进一步logistic回归分析显示,年龄≥65岁、冠心病、高脂血症、抗血小板药物、降糖药物是影响患者他汀药物治疗的独立危险因素(P0.05,P0.01)。结论缺血性脑卒中患者他汀类药物治疗率低,LDL-C达标率更低,应加强患者教育及临床医师培训,提高患者服用他汀类药物的依从性。     

合并糖尿病或胰岛素抵抗的缺血性卒中患者的抗血小板治疗

糖尿病是缺血性卒中患者抗血小板治疗后发生血小板高反应性的独立预测因素,而后者与卒中复发风险增高密切相关.糖尿病或胰岛素抵抗患者血小板反应性增高的机制与多种因素有关,一些血液循环分子可作为预测血小板反应性增高的标记物.监测新型抗血小板药治疗后的血小板反应性,可为合并糖尿病或胰岛素抵抗的缺血性卒中患者的个体化抗栓治疗提供依据.     

缺血性卒中二级预防的药物依从性调查

目的评估缺血性卒中患者抗血栓药物和危险因素用药的依从性、停药和药物变更原因及影响因素。方法通过电话随访获得卒中患者出院后1年时用药等方面的情况。结果2002年10月至2003年4月北京天坛医院神经内科缺血性卒中患者412例,其中374例患者进入调查,其中完成电话随访者296例(79.1%)。患者抗血栓药物的依从性为35.1%;伴有高血压、糖尿病和高血脂患者1年后仍接受治疗者的比例分别为77.9%、80.2%和48.4%。医保或公费(OR2.117,95%CI1.174～3.821)可促进患者对药物的依从,非阿司匹林抗血栓药物(OR0.352,95%CI0.153～0.812)和较低的日常生活能力指数(62.5±13.3)(MannWhitneyU检验,P=0.000)可明显降低卒中患者的药物依从性。结论卒中二级预防中药物依从性差主要表现为停药和剂量减小。支付方式、收入水平、抗血栓药物的种类以及患者的个人生活能力等可影响卒中患者的药物依从性。     

缺血性卒中或短暂性脑缺血发作的双重抗血小板治疗

2013年美国心脏协会/美国卒中协会颁布的缺血性卒中早期处理指南推荐单用阿司匹林进行抗血小板治疗,并未推荐其他抗血小板药,更未推荐联合应用多种抗血小板药.然而,2013年之后发表的大量文献显示,双重抗血小板药在防治缺血性卒中和短暂性脑缺血发作方面优于单个抗血小板药,并评估了双重抗血小板药治疗的安全性.     

Cost-effectiveness of new antiplatelet regimens used as secondary prevention of stroke or transient ischemic attack

BACKGROUND: Compared with aspirin alone, use of the new antiplatelet regimens, including aspirin combined with dipyridamole and clopidogrel bisulfate, has been found to further reduce the risk of stroke and other vascular events in patients who have experienced stroke or transient ischemic attack. However, their cost-effectiveness ratios relative to aspirin alone have not been estimated. METHODS: We developed a Markov model to measure the clinical benefits and the economic consequences of the following strategies to treat high-risk patients aged 65 years or older: (1) aspirin, 325 mg/d; (2) aspirin, 50 mg/d, and dipyridamole, 400 mg/d; and (3) clopidogrel bisulfate, 75 mg/d. Input data were obtained by literature review. Outcomes were expressed as US dollars per quality-adjusted life-year (QALY). RESULTS: The use of aspirin combined with dipyridamole was more effective and less costly compared with the use of aspirin alone, providing a gain of 0.3 QALY for a 65-year-old patient. This regimen remained cost-effective despite wide sensitivity analyses. Clopidogrel was more effective and more costly compared with aspirin alone, yielding a gain of 0.2 QALY with a marginal cost-effectiveness ratio of $26,580 per each additional QALY (patient aged 65 years). Sensitivity analyses demonstrated that the efficacy of clopidogrel and its cost were key factors in determining its cost-effectiveness ratio compared with aspirin, which exceeded $50,000 when its efficacy decreased by half or its cost doubled. CONCLUSION: To prevent stroke in high-risk patients, dipyridamole combined with aspirin was more effective and less costly than aspirin alone, and clopidogrel was cost-effective compared with current standards of medical practice, except in extreme scenarios.     

Update on antiplatelet therapy for stroke prevention

The high rates of mortality and long-term disability associated with ischemic stroke, coupled with its prevalence, necessitate good, long-term preventive strategies. Risk-factor management is effective for individuals with preclinical and clinical cerebrovascular disease. Patients suffering from a transient ischemic attack or stroke are particularly vulnerable to subsequent stroke. Most of these individuals are candidates for antiplatelet treatment to prevent a recurrence. Available antiplatelet therapies include aspirin, ticlopidine, and clopidogrel. The combination of low-dose aspirin plus extended-release dipyridamole has been shown to offer safe, effective antiplatelet therapy for appropriate patients. In the second European Stroke Prevention Study, the combination was found to be significantly more effective than either drug alone, at the cost of relatively few treatment-related adverse effects. This combination is currently recommended as one of the first-line treatments for stroke prevention after first transient ischemic attack or stroke.     

缺血性卒中的二级预防及其依从性

研究显示,缺血性卒中的二级预防依从性并不理想。在影响二级预防依从性的因素中,性别、年龄或病情严重程度与依从性的相关性尚无明确结论,但已婚、医疗报销比例较高、对疾病认识较好、早期干预、医生的重视程度和医患关系良好可改善缺血性卒中二级预防的依从性。     

Measurement of platelet aggregation during antiplatelet therapy in ischemic stroke

Aspirin, ticlopidine and clopidogrel are used as a pharmacological means to efficiently decrease the number of reoccurrence of ischemic stroke (100-325 mg/d). This antiplatelet treatment could prevent the secondary stroke by approximately 22%. Laboratory effective platelet inhibition for the clinician, and methods for routine screening evaluation for the laboratory were studied. (1) For the standardisation of platelet aggregation technology blood samples of 150 healthy persons were studied in 5 centres. CARAT TX computerised optical aggregometer was used for measuring with collagen (2 microg/ml), epinephrine (10 microM), arachidonic acid 0.5 mM and ADP 5 microM as inductors. (2) Laboratory tests were compared in each centres performed in platelet-rich plasma of ischemic cardiovascular and stroke patients (n=823) taking 100-325 mg aspirin/d. (3) Blood samples of 555 ischemic stroke patients treated with aspirin (100-325 mg/d), 96 patients treated with ticlopidine (500 mg/d), and 67 patients treated with clopidogrel (75 mg/d) were evaluated, respectively.(1) The mean of maximal aggregation (%) - 2SD of untreated controls (n=150) were detected for collagen with 64%, epinephrine 59% and ADP 62%. (2) In 823 aspirin treated patients were found similar inhibition in different centres with same methods for standardisation. The mean inhibition level was in case of collagen 38%, epinephrine 37% and ADP 61%. (3) The distribution of ineffective platelet inhibition was detected in 17% of aspirin group (collagen and epinephrine), 4% of ticlopidine and 18% of clopidogrel group with ADP, respectively. Our findings were in the stroke cohort: effective inhibition levels: 36% in aspirin group, 73% in ticlopidine and 25% treated with clopidogrel. Platelet aggregation tests could help to find the optimal, and "custom taylored" dose of antiaggregating drugs in the secondary prevention of ischemic stroke.