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。     

Primary and secondary stroke prevention with antiplatelet drugs

Aspirin is not effective in the primary prevention of stroke. Patients with TIA or ischemic stroke carry a risk of recurrent stroke between 5 and 20% per year. In patients with TIA or ischemic stroke of noncardiac origin antiplatelet drugs are able to decrease the risk of stroke by 11-15% and the risk of stroke, MI and vascular death by 15-22%. Aspirin is the most widely used drug. It is affordable and effective. Low doses of 50-325 mg aspirin are as effective as high doses and cause less gastrointestinal side effects. Severe bleeding complications are dose-dependent. The combination of aspirin with slow release dipyridamole is superior to aspirin alone for stroke prevention. Clopidgrel is superior to aspirin in patients at high risk of recurrence. The combination of aspirin plus clopidogrel is not more effective than clopidogrel alone but carries a higher bleeding risk. None of the antiplatelet agents is able to reduce mortality.     

Update on the treatment and prevention of ischaemic stroke

SUMMARY

Stroke continues to have a devastating impact on public health. Recent epidemiological studies suggest that stroke is becoming more common, perhaps due to the ageing of the population and increased survival of patients with cardiac disease. There are specific and well-defined risk factors in patients with stroke, the most important being hypertension. Treatment options to reverse the effect of acute ischaemic stroke are limited. The only approved therapy is intravenous tissue plasminogen activator (tPA). The disadvantage of tPA treatment is a rate of symptomatic haemorrhage of about 6%. Newer stroke prevention options are currently being investigated including statins, oestrogen, angiotensin converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs). The challenge for physicians is to select the most effective intervention, and this depends on our knowledge of the underlying stroke mechanism and the patient's risk factors.     

Update on the treatment and prevention of ischaemic stroke

Stroke continues to have a devastating impact on public health. Recent epidemiological studies suggest that stroke is becoming more common, perhaps due to the ageing of the population and increased survival of patients with cardiac disease. There are specific and well-defined risk factors in patients with stroke, the most important being hypertension. Treatment options to reverse the effect of acute ischaemic stroke are limited. The only approved therapy is intravenous tissue plasminogen activator (tPA). The disadvantage of tPA treatment is a rate of symptomatic haemorrhage of about 6%. Newer stroke prevention options are currently being investigated including statins, oestrogen, angiotensin converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs). The challenge for physicians is to select the most effective intervention, and this depends on our knowledge of the underlying stroke mechanism and the patient's risk factors.     

Atorvastatin in prevention of stroke and transient ischaemic attack

Besides blood pressure-lowering drugs and, in certain circumstances, antithrombotic agents, statins are among the most effective drugs in reducing the risk of stroke in populations of patients at high vascular risk, as well as the risk of major coronary events. In secondary prevention of stroke, statins clearly reduced the risk of major coronary events. In the SPARCL (Stroke Prevention by Aggressive Reduction in Cholesterol Levels) trial, compared with placebo, the patients with a recent stroke or transient ischaemic attack without coronary heart disease randomised to atorvastatin 80 mg/day had a significant 16% relative risk reduction of stroke and a 35% reduction in the risk of major coronary events. This was obtained despite the fact that 25% of patients allocated to the placebo arm were prescribed a commercially available statin outside the trial. A post-hoc analysis used blinded low-density lipoprotein cholesterol (LDL-C) measurements (taken at study visits during the trial) as a marker of adherence to lipid-lowering therapy. Compared with the group with no change or an increase in LDL-C (the group adherent to placebo or not taking a statin), the group with ≥ 50% reduction in LDL-C had a significant 31% reduction in the risk of stroke. The next step is to define whether or not achieving a LDL-C of < 70 mg/dl is better than a standard dose of statin (LDL ～ 100 – 110 mg/dl) in the secondary prevention of stroke. Statins are effective in reducing both first-ever and recurrent stroke, and this effect seems driven by the extent of LDL-C lowering.     

Atorvastatin in prevention of stroke and transient ischaemic attack

Besides blood pressure-lowering drugs and, in certain circumstances, antithrombotic agents, statins are among the most effective drugs in reducing the risk of stroke in populations of patients at high vascular risk, as well as the risk of major coronary events. In secondary prevention of stroke, statins clearly reduced the risk of major coronary events. In the SPARCL (Stroke Prevention by Aggressive Reduction in Cholesterol Levels) trial, compared with placebo, the patients with a recent stroke or transient ischaemic attack without coronary heart disease randomised to atorvastatin 80 mg/day had a significant 16% relative risk reduction of stroke and a 35% reduction in the risk of major coronary events. This was obtained despite the fact that 25% of patients allocated to the placebo arm were prescribed a commercially available statin outside the trial. A post-hoc analysis used blinded low-density lipoprotein cholesterol (LDL-C) measurements (taken at study visits during the trial) as a marker of adherence to lipid-lowering therapy. Compared with the group with no change or an increase in LDL-C (the group adherent to placebo or not taking a statin), the group with >or= 50% reduction in LDL-C had a significant 31% reduction in the risk of stroke. The next step is to define whether or not achieving a LDL-C of < 70 mg/dl is better than a standard dose of statin (LDL approximately 100 - 110 mg/dl) in the secondary prevention of stroke. Statins are effective in reducing both first-ever and recurrent stroke, and this effect seems driven by the extent of LDL-C lowering.     

Economic assessment of the secondary prevention of ischaemic stroke with dipyridamole plus aspirin (Aggrenox/Asasantin) in France

OBJECTIVE: To assess the cost effectiveness of aspirin 25 mg plus dipyridamole 200 mg twice daily in the secondary prevention of ischaemic stroke, according to the French social security perspective, using efficacy data from the second European Stroke Prevention Study (ESPS-2). The ESPS-2 was a double-blind, placebo-controlled clinical trial which assessed the efficacy of four secondary prevention strategies: (i) placebo; (ii) aspirin (acetylsalicylic acid) 25 mg twice daily; (iii) dipyridamole 200 mg twice daily; and (iv) aspirin 25 mg plus dipyridamole 200 mg twice daily. METHOD: We performed a cost-effectiveness analysis with Monte Carlo simulations to compute confidence intervals. We combined data from various sources including the Dijon Stroke Registry, Institut National de la Statistique et des Etudes Economiques, Etude du Co?t de l'Infarctus Cérébral (Study of the Cost of Cerebral Infarction [ECIC]) study and the ESPS-2 trial. RESULTS: According to our findings, a preventive strategy with aspirin 25 mg plus dipyridamole 200 mg twice daily is associated with net benefits per avoided stroke recurrence amounting to USD 23,932 (95% CI -USD 32,609, USD 35,772) compared with aspirin 25 mg twice daily alone, and USD 31,555 (95% CI USD 4921, USD 74,515) compared with dipyridamole alone (1997 values). Sensitivity analysis demonstrated that dipyridamole plus aspirin was still cost effective when the average cost of adverse effects per episode (ignored in the original estimation of the cost-effectiveness ratios due to a lack of data) was assumed to be USD 8600 (50,000 French francs); this cost is unlikely as most of the adverse effects associated with aspirin plus dipyridamole are only slight to moderate in severity. CONCLUSIONS: In the secondary prevention of stroke in France, this study suggests, given its underlying assumptions and data, that aspirin 25 mg plus dipyridamole 200 mg twice daily is likely to be a cost-effective strategy from the social security perspective, when compared with other relevant strategies that were evaluated in the ESPS-2 trial.     

Economic assessment of the secondary prevention of ischaemic events with lysine acetylsalicylate

OBJECTIVE: To analyse the economic benefits, in comparison with placebo, of the secondary prevention of ischaemic stroke and myocardial infarction (MI) with lysine acetylsalicylate (Kardégic) in patients with a history of ischaemic stroke, MI or stable and unstable angina pectoris. DESIGN AND SETTING: This was a modelling study from the perspectives of direct medical costs, the social security system and society in France. METHODS: Efficacy data for the secondary prevention of ischaemic events were derived from the Antiplatelet Trialists' Collaboration meta-analysis on antithrombotics. The rates and costs of ischaemic disease and of serious gastrointestinal adverse affects arising from long term aspirin treatment, as well as the costs of treatment with lysine acetylsalicylate, were taken from published sources, using French data where possible. RESULTS: From the social security perspective, the estimated cost-effectiveness ratios show that the prevention of MI in patients with a history of unstable angina (with a 1-year follow-up) is a cost-saving strategy, with net benefits ranging from $US5703 (1996 prices) per avoided MI for lysine acetylsalicylate 300 mg/day to $US5761 per avoided MI for lysine acetylsalicylate 75 mg/day. The prevention of MI and stroke is also a cost-saving strategy in patients with prior MI [net benefits in a 2-year follow-up (5% discount rate) ranging from $US15 to $US494 per avoided MI and from $US37 to $US1170 per avoided stroke]. This was also true in patients with prior ischaemic stroke (net benefits in a 3-year follow-up ranging from $US610 to $US2082 per avoided MI and from $US176 to $US599 per avoided stroke). Finally, a 4-year follow-up in patients with a history of stable angina pectoris shows that prophylactic treatment with lysine acetylsalicylate is associated with net costs per avoided MI, ranging from $US4375 to $US3608 per avoided event. Sensitivity analysis confirmed that prophylaxis with lysine acetylsalicylate in patients at high risk of cardiovascular and cerebrovascular events results in savings in social security expenditure. CONCLUSIONS: Our results underline the high economic benefit of using lysine acetylsalicylate to prevent secondary ischaemic stroke and MI in patients at high risk of cardiovascular and/or cerebrovascular events, leading to savings for the social security system and society.     

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.     

Clopidogrel in secondary ischemic stroke prevention

The results obtained in the CAPRIE study in 1996 led to the introduction of the clopidogrel as a new antiplatelet drug in the secondary prevention of acute myocardial infarct (AMI), ischemic stroke (IS) and symptomatic peripheral artery disease (PAD). Clopidogrel showed a similar efficacy and safety than acetylsalicylic acid (ASA). More recently, the combined use of clopidogrel with ASA has evidenced a better protection than ASA alone in some patients: patients with past history of AMI, angina pectoris, intermittent claudication or PAD, IS or TIA, coronary bypass, and diabetes mellitus, patients on treatment with statins, and patients with symptomatic carotid stenosis >/=50%. We review the reported evidence on the efficacy of clopidogrel in the secondary prevention of ischemic stroke.     

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.     

Clopidogrel for the secondary prevention of stroke

Patients suffering a transient ischaemic attack (TIA) or ischaemic stroke (IS) have a high risk of recurrence. The inhibition of platelet function is effective in the reduction of secondary vascular events in patients with TIA or stroke. This is true for acetylsalicylic acid (ASA), clopidogrel, ticlopidine and the combination of ASA plus slow-release dipyridamole. This overview analyses the results of recent trials and presents ongoing or future trials with clopidogrel as well as the combination of clopidogrel plus ASA. Clopidogrel is superior to ASA in the prevention of vascular events in patients with IS, myocardial infarction (MI) or peripheral arterial disease (PAD). The difference is highest for high-risk patients such as diabetics, patients who underwent coronary bypass surgery and patients with a remote prior history of ischaemic events. A prediction model is presented which allows the identification of patients in whom clopidogrel is superior to ASA for the secondary prevention of stroke. The combination of clopidogrel and ASA is better than ASA alone in patients undergoing coronary stent implantations and patients with unstable angina or non-Q-wave MI. In high-risk patients with TIA or stroke, the addition of ASA to clopidogrel is not superior to ASA monotherapy but results in a higher rate of bleeding complications. The long-term combination therapy is currently investigated in several large trials in > 30,000 patients, with a large number of stroke patients.     

低分子肝素防治急性缺血性卒中合并下肢深静脉血栓的临床研究

目的探讨低分子肝素防治急性缺血性卒中合并下肢深静脉血栓(deep-vein thrombosis,DVT)的临床效果。方法选择我院收治急性缺血性脑卒中患者200例,将其分为实验组和对照组,每组100例。实验组患者在常规治疗的基础上给予低分子肝素(low-molecular-weight hep-arins,LMWH)5000u进行腹部皮下注射,每12h注射1次,连用14d;实验组患者仅作常规治疗。对比两组患者的治疗效果,治疗期间和治疗后3个月内的临床结局以及不良反应,观察DVT的发生率。结果治疗两个疗程后,实验组有效率为89.0%,对照组有效率为80.0%,实验组疗效明显优于对照组(P<0.05);治疗期间以及治疗后3个月实验组DVT的发生率为11.0%,对照组DVT的发生率为26.0%,两者差异有显著性(P<0.01),实验组患者的PE发生率、出血性阻塞发生率和死亡率也显著低于对照组;实验组和对照组不良反应的发生率相似,实验组为81.0%,实验组为86.0%,两者无统计学差异,实验组患者没有出现严重的出血并发症。结论低分子肝素可有效降低急性缺血性脑卒中患者下肢深静脉血栓的发病率,值得临床推广使用。     

氟西汀对急性缺血性脑卒中伴言语障碍患者运动功能康复的影响

目的 观察伴有言语障碍的急性缺血性脑卒中患者预防性应用抗抑郁药盐酸氟西汀分散片对运动功能康复的影响.方法 将80例伴有言语障碍的缺血性脑卒中患者完全随机分为观察组和对照组,各40例,2组均给予急性缺血性脑卒中常规治疗如抗血小板聚集、危险因素控制、稳定动脉粥样硬化斑块等.观察组加用盐酸氟西汀分散片20 mg/次,1次/d,晨服,基本疗程为3个月.卒中起病后7d内、90d,采用简化Fugl-Meyer运动功能评分(FMMS)评价运动功能,美国国立卫生研究院卒中量表(NIHSS)、日常生活Barthel指数(Barthel index) 10项评价患者的神经功能损害程度和日常生活活动能力.结果 观察组患者40例中,l例死亡(肺炎),2例退出,有效例数37例;对照组40例患者中,2例失访,有效例数为38例.卒中后90 d,观察组上、下肢FMMS评分分别为(30±22)、(24±8)分,高于对照组的(16±17)、(19±8)分;上、下肢FMMS增加分数分别为(24±20)、(12±5)分,高于对照组的(12±15)、(10±4)分;组间差异均有统计学意义(P＜0.05).卒中后90 d,观察组NIHSS评分明显低于对照组[(6±4)分比(11±4)分],Barthel指数明显高于对照组[(56±10)分比(50±9)分],差异均有统计学意义(均P＜0.01).结论 预防性应用抗抑郁药氟西汀分散片可以促进伴有言语障碍的缺血性脑卒中患者的运动功能康复,提高总体康复水平.     

Combination antiplatelet agents for secondary prevention of ischemic stroke

Stroke is a leading cause of death and the primary cause of serious, long-term disability in the United States. Joint guidelines from the American Heart Association (AHA) and American Stroke Association (ASA), as well as recent guidelines from the Eighth American College of Chest Physicians (ACCP) Conference on Antithrombotic and Antiplatelet Therapy, recommend aspirin, clopidogrel, or extended-release dipyridamole plus aspirin as acceptable first-line options for secondary prevention of ischemic events in patients with a history of ischemic stroke or transient ischemic attack (TIA). The ACCP strongly recommends the combination of extended-release dipyridamole plus aspirin over aspirin monotherapy (highest level of evidence) and suggests clopidogrel monotherapy over aspirin monotherapy (lower level of evidence). The AHA-ASA guidelines suggest that either extended-release dipyridamole plus aspirin or clopidogrel monotherapy should be used over aspirin monotherapy. Both guidelines recommend avoiding the combination of clopidogrel and aspirin for most patients with previous stroke or TIA. Results from recent trials evaluating combination antiplatelet therapy have been published that enhance the AHA-ASA recommendations and provide the foundation for the updated ACCP guideline. To identify pertinent combination antiplatelet trials, a MEDLINE search of the literature from 1967-2007 was performed. Two trials were identified--the European-Australasian Stroke Prevention in Reversible Ischemia Trial (ESPRIT) and Clopidogrel for High Atherothrombotic Risk and Ischemic Stabilization, Management, and Avoidance (CHARISMA). The ESPRIT compared aspirin monotherapy with the combination of aspirin plus extended-release dipyridamole for prevention of secondary ischemic events in patients with a history of TIA or minor stroke. The CHARISMA trial compared aspirin plus clopidogrel with aspirin alone in a population at high risk for atherothrombotic events using the composite outcome of myocardial infarction, stroke, and death from cardiovascular causes. Data from ESPRIT add to evidence that the combination of aspirin plus extended-release dipyridamole is superior to aspirin alone. The findings of the CHARISMA trial reinforce recommendations from both AHA-ASA and ACCP that the combination of aspirin and clopidogrel be reserved for special populations requiring this antiplatelet combination (e.g., those who have had coronary artery stenting).     

Antiplatelet drugs in cardiovascular prevention: stroke: acute phase and secondary prevention

(1) In the acute phase of ischaemic stroke in patients free of thrombogenic heart disease, combined treatment with aspirin + moderate-dose unfractionated heparin reduces the risk of relapse and death. Unfractionated heparin at higher anticoagulant doses has an unfavourable risk-benefit ratio. Treatment is controversial in patients with events associated with atrial fibrillation. (2) After ischaemic stroke in patients free of thrombogenic heart disease, aspirin reduces the risk of relapse and death. Other antiplatelet drugs, the aspirin + dipyridamole combination, ticlopidine and clopidogrel have similar efficacy to aspirin. (3) The risk-benefit ratio of oral anticoagulant is favourable after ischaemic stroke associated with atrial fibrillation; but it is unfavourable after stroke without thrombogenic heart disease.     

Adverse effects and drug interactions of antithrombotic agents used in prevention of ischaemic stroke

Stroke is the third most common cause of death in the US. Primary prevention of stroke can be achieved by control of risk factors including hypertension, diabetes mellitus, elevated cholesterol levels and smoking. Approximately one-third of all ischaemic strokes occur in patients with a history of stroke or transient ischaemic attack (TIA). The mainstay of secondary prevention of ischaemic stroke is the addition of medical therapy with antithrombotic agents to control the risk factors for stroke. Antithrombotic therapy is associated with significant medical complications, particularly bleeding.Low-dose aspirin (acetylsalicylic acid) has been shown to be as effective as high-dose aspirin in the prevention of stroke, with fewer adverse bleeding events. Aspirin has been shown to be as effective as warfarin in the prevention of noncardioembolic ischaemic stroke, with significantly fewer bleeding complications. Ticlopidine may be more effective in preventing stroke than aspirin, but is associated with unacceptable haematological complications. Clopidogrel may have some benefit over aspirin in preventing myocardial infarction, but has not been shown to be superior to aspirin in the prevention of stroke. The combination of clopidogrel and aspirin may be more effective than aspirin alone in acute coronary syndromes, but the incidence of adverse bleeding is significantly higher. Furthermore, the combination of aspirin with clopidogrel has not been shown to be more effective for prevention of recurrent stroke than clopidogrel alone, while the rate of bleeding complications was significantly higher with combination therapy. The combination of aspirin and extended-release dipyridamole has been demonstrated to be more effective than aspirin alone, with the same rate of adverse bleeding complications as low-dose aspirin. When selecting the appropriate antithrombotic agent for secondary prevention of stroke, the adverse event profile of the drug must be taken into account when assessing the overall efficacy of the treatment plan.     

脑卒中后细发性癫痫21例临床分析

目的 探讨癫痫与脑卒中的关系、继发性癫痫的特点及其治疗.方法 对223例脑卒中患者进行观察,对卒中后继发性癫癇21例患者的临床资料进行分析.结果 脑卒中后继发性癫癇患者多见于脑皮质卒中患者,其中脑皮质卒中组癫癇发生率为16.7%,明显高于皮质下脑卒中组癫痫发生率（5.%）,两组差异有统计学意义（P＜0.01）.＞4 cm的脑卒中病灶组癫痫发生率为17.3%,明显高于＜4 cm脑卒中病灶组癫痫发生率（5.4%）（P＜0.01）.出血性卒中组和缺血性卒中组癫痫发生率差异无统计学意义（P＞0.05）.结论 脑卒中后继发性癫痫的发生率与脑卒中类型无关,与脑卒中发生部位和面积有关.