脑血管病二级预防抗血小板药物研究进展

<正>脑血管病是我国居民首要的致残原因和第3位死亡原因,给我国卫生系统带来沉重负担,是影响我国居民健康的重大公共卫生问题^[1]。以阿司匹林为代表的抗血小板药物治疗是降低卒中事件复发的重要手段。本文对近几十年来脑血管病二级预防中抗血小板药物研究的发展过程和亟待解决的问题进行介绍,以期为抗血小板药物在脑血管病研究和临床中的应用提供思路和参考。     

抗血小板药物预防缺血性脑卒中的现状

脂质斑纹在 10～ 2 0岁时即可发现 ,2 0～ 40岁后脂质斑纹发展成纤维斑块 ,最后形成动脉粥样硬化斑块 ,这一时期可有心绞痛、TIA 和间歇性跛行 ,但在血栓形成以前多无症状 ,斑块破裂后血小板活化、聚集形成血栓 ,致缺血性脑卒中、心梗或血管性猝死等。抗血小板治疗可预防血栓形     

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。     

抗血小板聚集药物及他汀在脑梗死二级预防中的应用情况及对脑梗死复发的影响

目的 了解脑梗死患者二级预防中抗血小板聚集药物及他汀的应用情况、中断治疗的原因及脑梗死复发情况。方法 观察 2012年10月～2013年10月在上海长征医院及长征医院闸北分院神经内科就诊的180例初发脑梗死患者从脑梗死后1月到脑梗死后1年抗血小板药物及他汀的应用情况,并根据患者在长期的二级预防过程中是否规律服用抗血小板药物及他汀分为规律用药组(n=73)、单用抗血小板聚集药物组(n=80)、单用他汀组(n=9)、均未服用组(n=18),调查患者中断抗血小板药物及他汀的原因并比较4组患者脑梗死后1年的复发情况。结果 180例脑梗死患者中断抗血小板聚集治疗共有27例(15%),原因分别为不良反应19例(70.4%)、担心不良反应而不愿服用6例(22.2%)、医师未建议及门诊医师未开医嘱2例(7.4%); 中断他汀治疗共有 98 例(54.4%),原因分别为不良反应13例(13.3%)、担心不良反应而不愿服用27例(27.6%)、医师未建议及门诊医师未开医嘱25例(25.5%)、检测指标正常而自行停用30例(30.6%)、经济原因3例(3.1%); 脑梗死后1年脑梗死复发情况分别为规律用药组复发8例(11.0%)、单用抗血小板聚集药物组复发17例(21.3%)、单用他汀组复发2例(22.2%)、均未服用组复发6例(33.3%)。结论 脑梗死二级预防中抗血小板聚集药物应用较为普遍,他汀应用严重不足,抗血小板聚集联合他汀治疗脑梗死后复发率明显降低。     

阿司匹林联合双嘧达莫在缺血性脑卒中二级预防中的应用

脑卒中是世界范围内人口死亡的第三位病因和成人残疾的首要原因,同时,也是老年人认知功能障碍和情感障碍的重要病因之一。我国为脑卒中高发国家,年发病率为185～219/10万,估计每年有200万人新发卒中,约150万人死于脑卒中,存活700万     

阿司匹林对缺血性脑血管病患者抗血小板聚集作用的临床观察

阿司匹林是抗血小板聚集药物，广泛应用在心脑血管疾病的治疗和预防。本研究对日服阿刮匹林75mg的68例缺血性脑血管病（ICVD）患者通过测定其血小板聚集率观察阿司匹林的抗血小板聚集作用。     

伴脑出血史的缺血性卒中患者使用抗血小板药物二级预防的调查

目的 通过结局调查分析既往有脑出血史的缺血性卒中患者使用抗血小板药物(antiplatelet drugs,APD)的状况以及使用APD对再发脑出血和再发脑梗死的影响.方法 随访我院既往有过脑出血的脑梗死患者的单中心、回顾性队列研究.统计学方法采用生存曲线及Logistic回归分析APD对既往有过脑出血患者缺血性卒中二级预防结局的影响.结果 既往有过脑出血的缺血性卒中合并心房颤动和心肌梗死的患者在心内科就诊时更易接受服用APD.既往有过脑出血患者缺血性卒中二级预防中APD没有增加再发脑出血(OR=1.149,95%CI0.376～3.513,P=0.808);未良好控制的高血压和脑叶出血是再发脑出血的危险因素;APD的使用能明显降低再发脑梗死的发生(OR=0.410,95%CI0.203～0.826,P=0.013).既往有过脑出血的缺血性卒中患者服用APD再发脑出血间隔时间均值为39个月,未服APD患者为45个月(X2=1.257,P=0.262).既往有过脑出血的缺血性卒中患者服用APD再发脑梗死间隔时间均值为42个月,末服APD患者为22个月(X2=14.315,P=0.001).结论 既往有过脑出血的缺血性卒中患者,通过APD进行缺血性卒中二级预防可获益,再发肭出血未见增多.考虑到本调查中脑叶出血和高血压控制不良容易再发脑出血,使用APD时把血压控制在正常范围并排除既往有过脑叶出血的病例,也许是更为安全的选择.     

双重抗血小板治疗在预防进展性缺血性脑卒中的作用

脑梗死是神经内科的高发疾病,在急性期进展的发生率约20%～40%,进展性缺血性脑卒中预后不良。目前国内外对进展性脑卒中研究较多,但尚缺少双重抗血小板治疗与脑梗死进展发生的相关性研究,而且对双重抗血小板治疗的风险及获益尚无定论。本研究旨在探讨双重抗血小板治疗对急性脑梗死患者进展性脑卒中发生的影响。     

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。     

Lancet N：卒中二级预防长期双联抗血小板的突破

合并颈动脉和颅内动脉狭窄或多重血管危险因素的非心源性缺血性卒中患者复发风险很高。对于这一部分患者,综合预防治疗,包括抗血小板治疗,已经被证明是有益的。不过,新型抗血小板药物,比如替格瑞洛和普拉格雷,是治疗冠心病很有前景的药物,在临床应用大约10年了,但是在卒中患者的随机对照试验中并未发现它们优于传统的抗血小板药物。不同的抗血小板药物通过不同的机制发挥作用,联合用药比单药能更加有效地预防卒中。     

缺血性脑血管病二级预防他汀类药物应用现况调查

目的:了解北京市部分二级医院缺血性脑血管病二级预防他汀类药物应用现状,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,研究对象为北京市4家二级医院中诊断为急性动脉粥样硬化性脑梗死及短暂性脑缺血发作(TIA)的住院患者,调查患者住院期间以及出院3个月他汀类药物的应用现况。结果:入选患者共458例,其中408例完成了3月随访。住院期间他汀类药物的应用比率为35.6%;出院3月,他汀类药物的用药比率降为22.3%,与住院期间相比有明显差异(p<0.001);而依从性差的原因与患者的性别、经济负担、学历、危险因素的存在与否及脑血管病亚型(脑梗死或TIA)均无明显相关。3月随访发现缺血性脑血管事件发生率为4.9%(20例),冠脉综合征0.5%(2例),且22例血管事件复发患者中仅有9.1%(2例)坚持他汀治疗。结论:北京市部分二级医院脑血管病医生对他汀类调脂药用于缺血性脑血管病二级预防已经有了一定程度的认识,但与卒中降脂指南尚有距离,同时我们应对缺血性脑血管病患者他汀用于缺血性脑血管病二级预防的依从性给予关注。     

European stroke prevention study: effectiveness of antiplatelet therapy in diabetic patients in secondary prevention of stroke.

BACKGROUND AND PURPOSE: The European Stroke Prevention Study was a multicenter trial comparing the effect of a combination of 75 mg dipyridamole and 330 mg acetylsalicylic acid three times a day with the effect of a placebo in the prevention of stroke or death in 1,861 patients after one or more episodes of recent transient ischemic attack or cerebral infarction. METHODS: The present study represents a secondary analysis of the efficacy of study medication in diabetic (n = 216) and nondiabetic (n = 1,645) patients. RESULTS: The risk of end point events was greater in diabetic than in nondiabetic subjects. Total end point reduction in individuals receiving the combination of dipyridamole and acetylsalicylic acid was 39% in nondiabetic subjects and 23% in diabetic subjects in the explanatory analysis, and the reduction in the risk of stroke was 48% and 32%, respectively. However, a statistically significant reduction of risk was obtained only in nondiabetic subjects. CONCLUSIONS: The combination of dipyridamole and acetylsalicylic acid appeared to be more effective in nondiabetic subjects than in diabetic subjects in the prevention of death and stroke although the low number of diabetic patients may at least in part explain this result.     

缺血性脑血管病二级预防中阿托伐他汀应用分析

目的 了解缺血性脑血管病二级预防中阿托伐他汀的应用情况.方法 对动脉粥样硬化性脑梗死及短暂性缺血发作(TIA)患者479例及其出院6个月随访的422例,调查住院期间及出院6个月时阿托伐他汀的应用情况.结果 住院期间,患者阿托伐他汀钙的使用率为41.5%,脑梗死与TIA患者的使用率无显著统计学差异(40.8%对40.3%, P=0.9411).阿托伐他汀的使用率随基线LDL-C的增高而增高,但达标率呈下降趋势.出院6个月,阿托伐他汀的使用率、达标率分别降至28.7%和38.8%,与住院期间相比均明显降低(P=0.000,P=0.017).结论缺血性脑血管病二级预防中,阿托伐他汀的使用率及达标率均较低,临床实践与指南尚有差距.     

短暂性脑缺血发作患者血栓前状态的观察

目的 观察短暂性脑缺血发作（TIA）患者外周活血状态的改变。方法 应用布氏显微镜对18例TIA患者之末梢血的活血状态进行观察，并与0例正常体检者作对照。结果 TIA组外周血红细胞聚集率，白细胞活化率，血小板活化率及其变化程度，显著高于对照组（P＜0．001）。TIA组活血中，红细胞成串，链状及缗钱样改变较明显，白细胞胞体变 ，黏附，血小板聚集，可见血小板血栓，同时发现每个高倍视野下循环团块数明显增多。结论 TIA患者末梢血中的有形成分均有不同程度改变。布氏显微镜直观地反映了TIA患者的活血状态。可以为诊断，治疗提供较可靠的观察指标。     

The study of brain reserve using diamox perfusion - weighted MRI in TIA patients with major cerebral artery occlusive

目的 探讨颅内大动脉狭窄或闭塞TIA患者脑血流灌注和储备能力。方法 对7例经MRA联合TCD和/或DSA证实颅内大动脉狭窄或闭塞的TIA患者,进行基态MR-PWI显像,2日后再口服乙酰唑胺2g, 2小时后再行PWI显像,比较乙酰唑胺前后PWI上血流灌注参数。结果 5例患者基态PWI显示颅内存在血流灌注下降部位,乙酰唑胺后该部位血流灌注明显下降,其中2例还发现新的缺血部位。1例患者乙酰唑胺前后血流灌注无明显缺血改变。1例患者基态PWI显示左半球缺血, 乙酰唑胺后双侧脑叶无明显变化,未发现明显缺血。 结论 乙酰唑胺前后PWI可以显示颅内动脉狭窄TIA患者颅内有无血流灌注或储备能力下降,为该类患者临床诊治提供依据。     

Psychopathology in postinfarction patients implanted with cardioverter-defibrillators for secondary prevention. A cross-sectional, case-controlled study

Objective

To determine (1) the incidence of anxiety and depression in patients implanted with defibrillators for secondary arrhythmia protection after myocardial infarction; (2) the effect of comorbidity and receipt of shock therapy on psychosocial maladjustment.

Methods

Cross-sectional, one-off, questionnaire-based (HADS; MOS SF-36), case-controlled study of defibrillator recipients (n=100) from a 3-year implant period and three groups of matched controls [pacemaker (n=50), coronary intervention (n=50), atrial fibrillation (n=50)], sharing specific preselected previous health experiences. Spouses of each subgroup (n=106) were also studied. Although a cardiac rehabilitation program was available routinely for postinfarction patients, no specific rehabilitation was provided after defibrillator or pacemaker implant.

Results

Mean scores for each assessment were similar for each group. Individual patient scores, however, revealed similarly high incidences of anxiety (24–34%) and depression (14–22%) in all groups. Experience of implantable cardioverter-defibrillator (ICD) ‘shock(s)’ and ‘shock storm(s)’ (≥3 shocks in 24 h) increased anxiety significantly. HADS criteria for anxiety ‘caseness’ or borderline ‘caseness’ were met in 63.6% of shock-storm recipients. Abnormal anxiety scores did not differ with interval from index event. Individual HADS scores also identified high incidences of anxiety in all spouse groups (25–48%).

Conclusions

Experience of shock storm precipitates pathological levels of anxiety in ICD recipients, and need for an ICD contributes to spouse anxiety. Individual CBT is indicated for patients who experience multiple shocks along with psycho-education for spouses. Anxiolytic and antidepressant medications may be indicated as part of their psychological rehabilitation.     

Psychopathology in postinfarction patients implanted with cardioverter-defibrillators for secondary prevention. A cross-sectional,case-controlled study

ObjectiveTo determine (1) the incidence of anxiety and depression in patients implanted with defibrillators for secondary arrhythmia protection after myocardial infarction; (2) the effect of comorbidity and receipt of shock therapy on psychosocial maladjustment.MethodsCross-sectional, one-off, questionnaire-based (HADS; MOS SF-36), case-controlled study of defibrillator recipients (n=100) from a 3-year implant period and three groups of matched controls [pacemaker (n=50), coronary intervention (n=50), atrial fibrillation (n=50)], sharing specific preselected previous health experiences. Spouses of each subgroup (n=106) were also studied. Although a cardiac rehabilitation program was available routinely for postinfarction patients, no specific rehabilitation was provided after defibrillator or pacemaker implant.ResultsMean scores for each assessment were similar for each group. Individual patient scores, however, revealed similarly high incidences of anxiety (24–34%) and depression (14–22%) in all groups. Experience of implantable cardioverter-defibrillator (ICD) ‘shock(s)’ and ‘shock storm(s)’ (≥3 shocks in 24 h) increased anxiety significantly. HADS criteria for anxiety ‘caseness’ or borderline ‘caseness’ were met in 63.6% of shock-storm recipients. Abnormal anxiety scores did not differ with interval from index event. Individual HADS scores also identified high incidences of anxiety in all spouse groups (25–48%).ConclusionsExperience of shock storm precipitates pathological levels of anxiety in ICD recipients, and need for an ICD contributes to spouse anxiety. Individual CBT is indicated for patients who experience multiple shocks along with psycho-education for spouses. Anxiolytic and antidepressant medications may be indicated as part of their psychological rehabilitation.     

Comparison of secondary vascular prevention in practice after cerebral ischemia and coronary heart disease

BACKGROUND: Secondary prevention measures in patients with cerebral ischemia or coronary heart disease (CHD) consist of vascular risk factors management and antithrombotic therapy. The aim of this study was to compare how secondary prevention measures are applied in practice between patients with a history of CHD or cerebral ischemia. METHOD: We compared vascular risk factors management and antithrombotic therapy between patients with a history of CHD and patients with a history of cerebral ischemia that occurred 2 months to 6 years earlier. Whether patients were properly treated or not was determined by a comparison between their current treatments and European guidelines for stroke and CHD management. RESULTS: We included 107 consecutive patients with a history of cerebral ischemia and 85 consecutive patients with a history of CHD. We found that: (i). most patients did not receive an appropriate secondary prevention in both groups: 76 of 107 patients with previous cerebral ischemia (71 %) and 73 of 85 patients with CHD (85.9 %); (ii). identification of risk factors, such as hypercholesterolemia, diabetes mellitus and smoking, did not differ between both groups, but arterial hypertension was more frequent in CHD patients; (iii). an inappropriate management of risk factors was more frequent in patients with TIA vs. ischemic stroke, and angina pectoris vs. myocardial infarction; (iv). arterial hypertension and hypercholesterolemia were the 2 more frequent risk factors that were not properly treated; (v). more than half diabetic patients had hyperglycemia > or= 126 mg/dl in both groups; (vi). patients with previous CHD had twice more frequently stopped smoking than those with cerebral ischemia. CONCLUSION: Many patients were not properly treated in both groups, and differences between practice and guidelines were more frequent in the CHD group, where guidelines are more strict.