Aspirin and heparin in acute ischaemic stroke in older patients.

Over four-fifths of all strokes are due to thrombotic or embolic occlusion of cerebral arteries. There is a strong rationale for considering antithrombotic therapy for the treatment of patients with acute ischaemic stroke. Antiplatelet therapy with 150 to 300 mg of aspirin (acetylsalicylic acid) started within the first 48 hours of an ischaemic stroke improves patient outcome in the short and long term, with a low risk of adverse effects. Anticoagulants such as heparin may reduce the risk of developing deep venous thrombosis and pulmonary embolism in patients with stroke, but randomised controlled trials have demonstrated a significant and dose-dependent risk of intracranial haemorrhage. The routine use of parenteral anticoagulants, including unfractionated heparin, low-molecular-weight heparins and heparinoids in the acute phase of ischaemic stroke is not associated with any net short or long term benefit. Aspirin is, therefore, the antithrombotic drug of choice in the treatment of acute ischaemic stroke.     

Low molecular weight heparin in acute stroke

Potential therapeutic strategies in acute ischaemic stroke include reperfusion, prevention of thrombus extension and rethrombosis and neuroprotection. Heparins inhibit thrombin and factor X and therefore may have useful effects on arterial and venous thrombosis; they are effective in the prevention and treatment of deep vein thrombosis (DVT) and pulmonary embolism (PE) and in the prevention of myocardial infarction (MI) in patients with unstable angina. Low molecular weight heparins (LMWHs) and heparinoids are known to be more effective and have a safer profile than unfractionated heparins in patients with venous thromboembolic disease and coronary artery disease. However, their role in acute ischaemic stroke is less clear. The very large International Stroke Trial found that unfractionated heparin had no overall benefit in ischaemic stroke, whilst causing significant intracranial haemorrhage. A number of Phase II and III trials of LMWH have been assessed in acute ischaemic stroke. It remains unclear whether these agents are effective and safe in acute ischaemic stroke although they do reduce the risk of DVT and PE. A systematic review is now required in order to assess the safety and efficacy of LMWH in acute stroke.     

Low molecular weight heparin in acute stroke

Potential therapeutic strategies in acute ischaemic stroke include reperfusion, prevention of thrombus extension and rethrombosis and neuroprotection. Heparins inhibit thrombin and factor X and therefore may have useful effects on arterial and venous thrombosis; they are effective in the prevention and treatment of deep vein thrombosis (DVT) and pulmonary embolism (PE) and in the prevention of myocardial infarction (MI) in patients with unstable angina. Low molecular weight heparins (LMWHs) and heparinoids are known to be more effective and have a safer profile than unfractionated heparins in patients with venous thromboembolic disease and coronary artery disease. However, their role in acute ischaemic stroke is less clear. The very large International Stroke Trial found that unfractionated heparin had no overall benefit in ischaemic stroke, whilst causing significant intracranial haemorrhage. A number of Phase II and III trials of LMWH have been assessed in acute ischaemic stroke. It remains unclear whether these agents are effective and safe in acute ischaemic stroke although they do reduce the risk of DVT and PE. A systematic review is now required in order to assess the safety and efficacy of LMWH in acute stroke.     

Aspirin and heparin in pregnancy

Introduction: A pro-coagulant state during pregnancy can be involved in the occurrence of gestational vascular complications (GVCs) and venous thromboembolism (VTE).

Areas covered: Antithrombotic drugs are used to prevent GVCs and VTE. Aspirin is not efficacious to prevent recurrences in women with previous early loss, while it can prevent pre-eclampsia in some groups of women. Heparins are not effective in the prevention of early recurrent loss and there is uncertainty about their efficacy in women carrying inherited thrombophilias. They could be efficacious in the prevention of GVCs in carriers of inherited thrombophilias, as GVCs have heterogeneous causes, and future studies have to focus on more homogeneous groups of patients. Not enough data are available regarding prophylaxis with heparins to prevent pregnancy-related VTE, but an accurate risk stratification of women during pregnancy and puerperium is crucial for administering prophylaxis in moderate-/high-risk women. Aspirin does not improve live births after assisted reproductive technologies, while heparins increase the number of clinical pregnancies and live births.

Expert opinion: Aspirin is efficacious in the prevention of GVCs in women at risk for pre-eclampsia and in those with antiphospholipid antibodies syndrome. Heparins could give benefit to women at risk for GVCs and/or pregnancy-related VTE.     

急性缺血性卒中患者的阿司匹林抵抗与卒中严重程度和梗死体积的相关性

目的 观察急性缺血性脑卒中患者阿司匹林抵抗与卒中严重程度及梗死灶体积的相关性.方法将发病48 h内且同时服用阿司匹林1周以上的350例急性缺血性卒中患者纳入本研究,应用PL-11血小板功能分析仪测定血小板反应性,阿司匹林抵抗即治疗后血小板高反应性(HPR)定义为花生四烯酸诱导血小板最大聚集率(MAR-AA)大于35％.梗死灶体积采用磁共振弥散加权成像(DWI)计算软件,卒中严重程度采用NIHSS评分.结果 HPR见于26.6％卒中患者;阿司匹林抵抗组初始NIHSS评分显著高于阿司匹林敏感组(10 [IQR 4～ 15]比4[IQR 2～6],P＜0.001);阿司匹林抵抗组梗死体积显著高于阿司匹林敏感组(5.3 [1.2 ～ 9.6]比1.8[0.8～8.8],P＜0.01);多变量中位数回归分析显示HPR增加NIHSS评分中位数6分(95％ CI3.68 ～ 8.31,P＜0.001),增加DWI梗死体积中位数2.8 cm3(95％ CI0.6 ～ 6.2,P＜ 0.01).结论 阿司匹林抵抗增加急性缺血性卒中患者的严重程度及梗死灶体积.     

低分子肝素治疗急性缺血性中风疗效和安全性

目的:评价低分子肝素(LMWH)治疗急性缺血性中风的疗效和安全性.方法:入选病例均用低分子右旋糖苷作基础治疗,治疗组加用LMWH.治疗组:3例进展型短暂脑缺血发作(TIA)及31例发病48h内脑梗死,LMWH4100anti-XaIU,bid,腹壁sc,连续10d.对照组:31例脑梗死.采用中风评分法在用药后1mo进行总评价.用发光底物法测定LMWH浓度.结果:3例TIA症状很快缓解.治疗组的总有效率(90.3%)明显优于对照组(64.5%),P<0.05.同时,起病24h内开始LMWH治疗的显效率(84.2%)优于起病24～48h才开始LMWH治疗的显效率(41.7%),P<0.02.高峰和低谷血药浓度分别为(0.32±0.17)及(0.26±0.19)anti-XaIU.未发现出血倾向.结论:低分子肝素治疗急性缺血性中风是安全有效的.     

Aspirin,stroke and drug-drug interactions

Low-dose aspirin, alone or in combination, is recommended for the secondary prevention of acute non-cardioembolic ischemic stroke and transient ischemic attack, starting soon after the acute event.Clinically-relevant drug-drug interactions (DDIs) are a major concern of regulatory agencies and practicing physicians. Drug's pharmacodynamics and/or pharmacokinetics account for clinically-relevant DDIs that modify efficacy and/or safety of one or more of the co-administered drugs.Some non-steroidal anti-inflammatory drugs interact with aspirin pharmacodynamics by competing on the drug target, i.e. the platelet's cyclooxygenase-1 protein. Although the molecular mechanism(s) of this DDI and its effect on the degree of platelet inhibition in vitro and ex vivo are well unraveled, nevertheless, the extent to which this DDI impacts on long-term antithrombotic efficacy of aspirin in secondary prevention remains unclear. Aspirin pharmacokinetics does not involve critical cytochrome P450 enzymes nor efflux transporters, therefore clinically-relevant DDIs competing on pharmacokinetic pathways seem unlikely. The co-administration of antiplatelet drugs with serotonin storage reuptake inhibitors can create a synergistic effect with antiplatelet agents on platelet inhibition.Low-dose aspirin, alone or in combination with other antiplatelet agents, remains a cornerstone in treating cerebrovascular disorders. The relatively straightforward pharmacokinetics of aspirin limits DDIs, giving it a unique advantage over most antiplatelet drugs.     

低分子量肝素治疗进展型脑梗死及对血流变影响

目的:探讨低分子量肝素对进展型脑梗死的疗效及血流变影响.方法:将80例进展型脑梗死患者,随机分为治疗组40例,对照组40例.两组在治疗前后均行神经功能缺损评分和临床疗效评定,并观察其疗效及有关实验室指标,追踪随访1年.结果:治疗组的有效率明显高于对照组,不良反应轻微,PLT、APTT无明显变化,但血流变指标明显下降,1年内复发率明显小于对照组.结论:低分子肝素治疗进展型脑梗死疗效肯定,对于减少复发亦有一定作用,并可改善血流变.     

巴曲酶与低分子肝素钙对急性缺血性脑卒中患者的效果对比

目的对比分析巴曲酶与低分子肝素钙对急性缺血性脑卒中患者的治疗效果。方法选取于本院接受治疗的100例急性缺血性脑卒中患者作为观察对象,将入选对象随机分为两组,对照组采用低分子肝素钙治疗,观察组采用巴曲酶治疗,观察患者治疗效果。结果观察组50例患者均达到有效及以上效果,对照组50例患者总有效率为90.00%,观察组50例患者平均口眼歪斜、半身不遂等症状改善时间均明显小于对照组,观察组50例患者中有1例恶心,1例乏力,不良反应发生率为4.00%,对照组50例患者中,2例恶心,1例头晕,2例乏力,不良反应发生率为10.00%,治疗后24h与治疗后1周观察组患者FIB评分均明显大于对照组。结论急性缺血性脑卒中发生后患者比较常见症状为神经功能缺损与脑动脉闭塞等,需要及时给予规范化治疗,而低分子肝素钙与巴曲酶等药物均能够达到较好的治疗效果,对比之下巴曲酶所能够达到的促进患者各项临床症状的改善,且不会增加不良反应。     

Dexamethasone in acute stroke.

Over 13 months 118 patients admitted to hospital with acute stroke were allocated at random to treatment with either dexamethasone or placebo. At one year there was no significant difference in the numbers of survivors or in the quality of life between the two groups. The results suggest that there is no indication for the routine administration of dexamethasone to a heterogeneous group of patients with stroke.     

替格瑞洛对轻型急性脑卒中和TIA患者血小板功能的影响

目的　探讨Sonoclot法检测替格瑞洛对轻型急性缺血性脑卒中和短暂性脑缺血发作（TIA）患者血小板功能的影响。方法　选取81例轻型急性缺血性脑卒中和TIA患者,随机数字表法分为试验组（39例）和对照组（42例）。前者入院后予以替格瑞洛联合阿司匹林治疗,21 d后改为替格瑞洛片;后者入院后予以氯吡格雷联合阿司匹林治疗,21 d后改为氯吡格雷片。于入院时、治疗7 d和治疗90 d,用Sonoclot法检测2组患者的血小板功能。结果　（1）与对照组相比,试验组在治疗7 d的激活凝血时间（ACT）、达峰时间（TP）值升高,血小板功能（PF）值降低,治疗90 d的ACT值升高（P＜0.05）,治疗前后2组间凝血速率（CR）和最大凝血标记值（MCS）差异无统计学意义（P＞0.05）。（2）与入院时相比,2组治疗7 d和90 d的ACT和TP值升高,PF、MCS降低（P＜0.05）。（3）2组治疗后不良事件比较差异无统计学意义（P＞0.05）。结论　与氯吡格雷相比,替格瑞洛能更快地抑制轻型急性缺血性脑卒中或TIA患者血小板功能,且不增加主要出血事件。     

Dysphagia in acute stroke.

A prospective study was undertaken to define the incidence, duration, and consequences of dysphagia in an unselected group of 91 consecutive patients who had suffered acute stroke. The site of the present lesion and of any previous stroke was determined clinically and was confirmed by computed tomography of the brain or necropsy in 40 cases. Of 41 patients who had dysphagia on admission, 37 had had a stroke in one cerebral hemisphere. Only seven patients showed evidence of lesions in both hemispheres. Nineteen of 22 patients who survived a stroke in a hemisphere regained their ability to swallow within 14 days. Dysphagia in patients who had had a stroke in a cerebral hemisphere was associated in this study with a higher incidence of chest infections, dehydration, and death.     

Predicting outcome in acute stroke

The natural history of acute stroke is well defined. Predicting outcome in individuals, however, remains difficult, because prognostic studies examining associations between clinical signs or syndromes and outcome differ in patient selection, timing and choice of neurological assessments and outcome measures. Accuracy has been disappointing. Osler in 1892 stated that the 'course of the disease ... is dependent on the situation and extent of the lesion'. Until recently, it has not been possible to examine the stroke prognosis, using Osler's approach, with any great accuracy. The advent of diffusion weighted magnetic resonance imaging (DWI), which is highly sensitive to the pathophysiological changes underlying stroke, offers this possibility as it measures the site and extent of irreversible infarction. This review summarises the results of syndrome or sign-based predictive studies and shows how DWI may explain different outcomes in patients with identical neurological presentations, according to the 'situation and extent of the lesion'.     

Aspirin or amiloride for cerebral perfusion defects in cocaine dependence

Cocaine dependent (CD) patients have regional cerebral blood flow (rCBF) deficits that may be related to occlusion of blood vessels by vasoconstriction and abnormal platelet aggregation. This study determined whether aspirin, which reverses platelet aggregation, or amiloride, a vasodilator, significantly reversed this rCBF hypoperfusion. This 1-month randomized trial compared clusters of voxels with significant hypoperfusion in recently abstinent CD patients after aspirin (325 mg daily), amiloride (10 mg daily) or placebo treatment. Forty-nine primary CD patients and 18 non-drug abusing controls were compared using single photon emission computed tomography (SPECT) neuroimaging with 99mTc-hexamethyl-propyleneamine-oxime and statistical parametric mapping (SPM). Platelet aggregation to adenosine diphosphate (ADP) was examined after treatment to determine whether rCBF improvement was related to decreased platelet aggregation. Following treatment, areas of hypoperfusion were improved with amiloride, unchanged with aspirin, and worsened with placebo in comparison to baseline levels. Platelet aggregation after ADP showed no significant change during the month, but reduced rCBF significantly improved after 1-month treatment with amiloride compared with placebo and cocaine abstinence alone.     

Dosing of unfractionated heparin in acute coronary syndromes

Although the use of low-molecular-weight heparins for treatment of acute coronary syndromes (ACS) has increased in recent years, unfractionated heparin (UFH) remains the drug of choice for many patients and institutions. One reason is that this agent is safe for patients with renal dysfunction as well as those who undergo percutaneous coronary intervention or coronary artery bypass graft. The use of UFH is complicated by the increased risk of bleeding due to concurrent administration of numerous antiplatelet drugs in most patients with ACS, the limited data regarding ideal therapeutic range, and the wide variability of patient response. Knowledge regarding the optimal therapeutic range and how to achieve it efficiently may enable clinicians to improve clinical outcomes in patients with ACS. We reviewed and analyzed the available evidence to clarify how to best manage UFH therapy in patients with ACS. Current data support the use of a lower and narrower therapeutic range for patients with ACS than the range that is used for venous thromboembolism. Many factors in addition to weight affect patient response to UFH, including age, sex, diabetes mellitus, smoking status, and obesity.     

Putrescine catabolism in rats given heparin or aminoguanidine

Rats treated acutely with aminoguanidine, a potent inhibitor of diamine oxidase, or with heparin display reduced ability to metabolize 14C-putrescine to radioactive carbon dioxide. After either drug rats recover 50% of the ability to catabolize putrescine in 15--18 h. This is in close agreement with the half-time for recovery of diamine exidase activity, and indicates that putrecine-catabolizing ability of the rat reflects in a physiologically significant way the function of diamine oxidase in vivo.     

Treating acute ischemic stroke

Acute ischemic stroke (AIS) is a common disorder that has only one associated approved therapy: intravenous tissue plasminogen activator (iv t-PA). A limiting factor to the use of iv t-PA is that it must be initiated within 3 h of stroke onset. Efforts to expand the therapeutic time window are underway and include image evaluation of the ischemic penumbra to target those patients who are most appropriate for treatment. Intra-arterial t-PA is also used only in some treatment centers despite convincing proof of efficacy of this therapy. Devices to restore perfusion that have been approved in the US for recanalization exist, but these are not approved for use in stroke therapy. Many neuroprotective drugs have been evaluated as potential acute stroke therapies, but none have shown efficacy, hence the future of neuroprotection as a strategy for acute ischemic stroke therapy remains uncertain.