Secondary prevention of stroke

Stroke is a common disorder and a leading cause of disability and death. Ischaemia is a more common cause than haemorrhage and radiological imaging is required to accurately differentiate these. Some specific risk factors for stroke are non-modifiable--these include age, gender, racial and hereditary factors. Certain risk factors for ischaemic stroke can be identified and modification of these can be used for secondary prevention--examples include hypertension, heart diseases, atrial fibrillation, diabetes mellitus, dyslipidaemia, smoking, excessive alcohol consumption and carotid stenosis. Carotid endarterectomy is valuable in selected patients. In ischaemic stroke and transient ischaemic attack antithrombotic therapy is an option used in secondary prevention. In atrial fibrillation, warfarin should be used where possible in secondary prevention. When warfarin is contraindicated aspirin should be used. In other patients, an antiplatelet regime is appropriate--aspirin is commonly used and is the least expensive regime. Other antiplatelet agents such as dipyridamole, ticlopidine and clopidogrel may have a place. Younger patients with ischaemic stroke may have a thrombophilia state and should be appropriately investigated.     

Antiplatelet therapy in ischemic stroke

Stroke is the third leading cause of death and the leading cause of disability in the developed world. Atherothrombosis is the underlying condition that results in events leading to ischemic stroke and vascular death. Antiplatelet therapy is commonly used for both acute stroke and in secondary prevention. Numerous trials and meta-analyses have left little doubt that antiplatelet therapy effectively reduces stroke risk in patients with prior stroke or transient ischemic attack. Current antiplatelet agents include acetylsalicylic acid, clopidogrel, ticlopidine and extended release dipyridamole with low doses of acetylsalicyclic acid (aspirin). The optimum doses of antiplatelet drugs depend upon several variables, such as genetic and environmental factors, so that clinical and laboratory response for dosage varies for each patient. Recently, the correlation between the laboratory-measurable effect of antiplatelet agents and the clinical effectiveness on the mortality of ischemic stroke and cardiovascular patients has been documented. Due to the side effect of bleeding with different antithrombotic drugs, their future employment will be determined in combination with low dosages of each component. Laboratory-controlled, tailored drug therapy will be needed for long-lasting secondary prevention of ischemic stroke.     

Discharge prescription for ischemic stroke patients

Stroke is a major public health issue: it affects 120 000 people in France each year. The yearly recurrence rate is thought to reach 8 percent. Secondary prevention of stroke is thus crucial and focuses on controlling vascular risk factors most often associated with antiplatelet agents. Therapeutic objectives are set depending on the individual's global cardiovascular risk. The PROGRESS study has shown the relevance of systematic blood pressure lowering using an angiotensin-converting-enzyme inhibitor (perindopril) in combination with a diuretic (indapamide) in secondary prevention of stroke, including in normotensive patients. If possible, blood pressure should be below 130/85 mmHg. Statins are indicated in stroke patients with hypercholesterolemia, coronary heart disease, diabetes mellitus or carotid stenosis, the target LDL-cholesterol level being below 1 g/L (2.58 mmol/L). There is a wide consensus on treating patients with symptomatic carotid stenoses > or = 70 percent by thrombo-endarterectomy and stroke associated with atrial fibrillation by anticoagulants. Management should be global and include changes in dietary behavior, tobacco and/or alcohol withdrawal, and regular exercising. Patient-specific therapeutic education should be offered in order to improve compliance.     

An assessment of guidelines for prevention of ischemic stroke

OBJECTIVE: To compare methods and key management recommendations from recent stroke prevention guidelines. METHODS: Systematic review of guidelines for prevention of ischemic stroke published in English between 1996 and 2001 was conducted, and recommendations were independently abstracted and compared. RESULTS: Among 22 stroke prevention guidelines, information was provided about panel selection in 24%, funding source in 36%, consensus methods in 33%, and quantitative risk/benefit estimates in 38%. Eleven recommended anticoagulation for patients with atrial fibrillation at high risk for stroke, but eight different sets of criteria to identify high-risk patients were proposed. Recommendations regarding carotid endarterectomy for asymptomatic stenosis varied from general endorsement in a setting of low perioperative risk to routinely withholding surgery. All nine relevant guidelines endorsed aspirin in dosages between 50 and 325 mg/day for initial antiplatelet therapy following cerebral ischemia; six also suggested other antiplatelet agents as options for initial therapy. CONCLUSIONS: Current stroke prevention guidelines do not provide adequate methodologic information to permit assessment of their quality, potential bias, and clinical applicability. Management recommendations are relatively consistent but differ in several important areas.     

New modalities and aspects of antiplatelet therapy for stroke prevention

Antiplatelet therapy is indicated for secondary prevention of ischaemic stroke. The first-line antiplatelet agent is aspirin. The effect of aspirin is, however, very limited, and this limited effect of aspirin is argued with termed 'aspirin resistance'. Strategies against aspirin resistance may include alternative use of other antiplatelet agents, combination of aspirin with other antiplatelet agents and investigation into molecular targets to develop novel antiplatelet agents. Progress in antiplatelet therapy should be directed at further reducing the risk of ischaemic events including ischaemic stroke without increasing the risk of haemorrhagic events including haemorrhagic stroke.     

Multimodal endovascular reperfusion therapies: adjunctive antithrombotic agents in acute stroke

Pharmacologic and mechanical endovascular acute ischemic stroke therapy aims to recanalize occluded cerebral vessels to achieve improved clinical outcome. Several limitations to achieving this goal have been identified; one of the least discussed challenges in the literature is reocclusion. The intraprocedure and periprocedural roles of anticoagulation and antiplatelet agents in preventing reocclusion are unclear. In this review, the role of antiplatelet and anticoagulation agents as an adjunctive to acute ischemic stroke endovascular revascularization therapy is discussed.     

Guidelines for the prevention of stroke in patients with stroke or transient ischemic attack: a guideline for healthcare professionals from the american heart association/american stroke association

The aim of this updated statement is to provide comprehensive and timely evidence-based recommendations on the prevention of ischemic stroke among survivors of ischemic stroke or transient ischemic attack. Evidence-based recommendations are included for the control of risk factors, interventional approaches for atherosclerotic disease, antithrombotic treatments for cardioembolism, and the use of antiplatelet agents for noncardioembolic stroke. Further recommendations are provided for the prevention of recurrent stroke in a variety of other specific circumstances, including arterial dissections; patent foramen ovale; hyperhomocysteinemia; hypercoagulable states; sickle cell disease; cerebral venous sinus thrombosis; stroke among women, particularly with regard to pregnancy and the use of postmenopausal hormones; the use of anticoagulation after cerebral hemorrhage; and special approaches to the implementation of guidelines and their use in high-risk populations.     

Arterial ischemic stroke in childhood: the role of plasma-phase risk factors

The role of plasma-phase risk factors for stroke in the pediatric age group is presently unclear due to the lack of sufficiently large prospective studies, and due to the fact that these risk factors do not apply uniformly to newborns, children with sickle cell disease, and older children. Available evidence indicates that factor V Leiden, prothrombin 20210A, and lipoprotein (a) are all important in the pathogenesis of arterial ischemic stroke in older children, but the role of other plasma-phase risk factors remains uncertain. The contribution of these risk factors to newborn stroke and the stroke of children with sickle cell disease is similarly unclear, likely because the ischemia in affected children is predominantly due to nonhematologic perinatal events and erythrocyte adhesion to endothelium with obstruction of flow in the cerebral microcirculation, respectively. Evaluation of childhood stroke should, in our view, always be performed from the standpoint of the presenting clinical symptoms, diagnostic imaging, and determination of plasma-phase risk factors. Therapeutic anticoagulation and use of antiplatelet agents at present focus on the older child.     

Treatment of arterial and venous brain ischemia. Experts' recommendations: stroke management in the intensive care unit

With thrombolysis, intravenous alteplase (0.9 mg/kg body weight, maximum 90 mg), with 10% of the dose given as a bolus followed by a 60-minute infusion, is recommended within 4.5 hours of onset of ischemic stroke. When indicated, intravenous thrombolysis must be initiated as soon as possible. It is possible to use intravenous alteplase in patients with seizures at stroke onset, if the neurological deficit is related to acute cerebral ischemia. Intravenous alteplase can be discussed for use on a case-by-case basis, according to risk of bleeding, in selected patients under 18 years and over 80 years of age, although for the current European recommendations this would be an off-label use. In hospitals with a stroke unit, intravenous thrombolysis is prescribed by a neurologist (current French labelling) or a physician having the French certification for neurovascular diseases (outside the current French labelling). The patient must be monitored in the stroke unit or in case of multiple organ failure in an intensive and critical care unit. In hospitals without a stroke unit, thrombolysis must be decided by the neurologist from the corresponding stroke unit via telemedicine. It is recommended to perform brain imaging 24 hours after thromboysis. Intra-arterial thrombolysis can be contemplated on a case-by-case basis after multidisciplinary discussion within a 6-hour time window for patients with acute middle cerebral artery or carotid occlusions, and within a larger time window for patients with basilar artery occlusion, because of their very poor spontaneous prognosis. Mechanical thrombectomy can also be contemplated in the same situations. With antiplatelet agents, it is recommended that patients receive aspirin (160 mg-325 mg) within 48 hours of ischemic stroke onset. When thrombolysis is performed or contemplated, it is recommended to delay the initiation of aspirin or other antithrombotic drugs for 24 hours. The use of antiplatelet agents that inhibit the glycoprotein IIb/IIIa receptor is not recommended. Urgent anticoagulation using heparin, low-molecular-weight heparins or danaparoid with the goal to treat ischemic stroke patients is not recommended. Secondary prevention by anticoagulation can be used, immediately or within the first days, after minor ischemic stroke or TIA in patients with a high risk for cardioembolism, if uncontrolled hypertension is absent. In patients with large infarcts and a high risk for cardioembolism, the timing for initiating anticoagulation must be decided on a case-by-case basis. In patients with anticoagulation who had an ischemic stroke, the decision to temporarily stop or maintain anticoagulation must be made on a case-by-case basis, depending on thromboembolic risk, level of anticoagulation at stroke onset and estimated risk of hemorrhagic transformation. It is not recommended to use neuroprotective agents in ischemic stroke patients. Patients with cerebral venous thrombosis must be treated with therapeutic doses of heparin, even in case of concomitant intracranial hemorrhage related to cerebral venous thrombosis. If the patient's status worsens despite adequate anticoagulation, thrombolysis may be used in selected cases. The optimal administration route (local or intravenous), thrombolytic agent (urokinase or alteplase) and dose are unknown. There is currently no recommendation with regard to local thrombolytic therapy in patients with dural sinus thrombosis. Urgent blood transfusions are recommended to reduce hemoglobin S to <30% in patients with sickle cell disease and acute ischemic stroke.     

Choices in medical management for prevention of acute ischemic stroke

Stroke is a leading cause of death and disability. Although advances are being made in the treatment of acute ischemic stroke, its prevention is equally as important. Identification and management of risk factors are essential. Medical therapy is also helpful in the secondary prevention of ischemic stroke. There are currently four plateletantiaggregating agents used to prevent ischemic stroke: aspirin, aspirin plus dipyridamole, clopidogrel, and ticlopidine. The relevant studies proving their efficacy are noted, as are some of their similarities and differences. The use of warfarin is also discussed.     

Current strategies for ischemic stroke prevention: role of multimodal combination therapies

Stroke remains a global leading cause of death and long-term disability, highlighting the need for more effective treatment approaches. The majority of strokes are of ischemic origin, often caused by large- or small-artery atherothrombosis, or cardioembolism. Considering the systemic nature of the atherothrombotic disease process, stroke patients are at increased risk for ischemic events in several vascular territories: cerebral, coronary and peripheral. Due to the limited options for acute stroke therapies, stroke prevention is an important therapeutic approach. In addition to the management of modifiable risk factors such as hypertension, dyslipidemia and smoking through pharmacotherapy or lifestyle adjustments, anticoagulants, surgical and perhaps endovascular approaches are indicated in certain patients. Antiplatelet therapies using various agents are a cornerstone of secondary stroke prevention. To ensure the appropriate continuum of care after hospitalization for ischemic stroke, some interventions for the prevention of recurrent ischemic stroke should be initiated during the acute hospitalization setting and maintained in the out-patient setting.     

Cardioembolic stroke: an update

Embolism of cardiac origin accounts for about one fifth of ischaemic strokes. Strokes due to cardioembolism are in general severe and prone to early recurrence. The risk of long term recurrence and mortality are high after a cardioembolic stroke. Cardioembolism can be reliably predicted on clinical grounds but is difficult to document. MRI, transcranial doppler, echocardiogram, Holter monitoring, and electrophysiological studies increase our ability to identify the source of cardioembolism. Non-valvular atrial fibrillation is the commonest cause of cardioembolic stroke. Despite its enormous preventive potential, continuous oral anticoagulation is prescribed for less than half of patients with atrial fibrillation who have risk factors for cardioembolism and no contraindications for anticoagulation. Alternatives to oral anticoagulation in this setting include safer and easier to use antithrombotic drugs and definitive treatment of atrial fibrillation. Available evidence does not support routine immediate anticoagulation of acute cardioembolic stroke.     

Antithrombotic treatments in acute ischemic stroke

A therapeutic role for antiplatelet agents and anticoagulants within 6 hours of the onset of ischemic stroke symptoms has not been tested. With one exception, their use in early stroke (< 48 hours) did not produce a favorable outcome. The use of rt-PA in appropriate patients presenting with ischemic stroke within 3 hours of symptom onset has been accompanied by significant benefit, which has exceeded the risk of intracerebral hemorrhage in one trial. The recent group of clinical studies has provided evidence for factors which may contribute to hemorrhagic transformation. These studies also demonstrate the following: i) recanalization of carotid and vertebrobasilar artery territory occlusions is technically feasible within 3 to 6 hours of symptom onset, ii) the frequency of hemorrhage is increased in ischemic stroke patients receiving PAs, iii) the interval from symptom onset to treatment to achieve clinical improvement varies individually and contributes to hemorrhagic risk, and iv) the optimal PAs, their dose-rate, and delivery systems have not yet been defined in either the carotid or vertebrobasilar territory. Taken together, the NINDS trial, ECASS, and ECASS II indicate the enormous importance of patient selection to reduce the hemorrhagic risk which accompanies the use of PAs in stroke. However, it is currently not possible to separate benefit from hemorrhagic risk in a given patient based upon simple clinical criteria, although contributors to this risk have been identified. Clearly, attempts to reduce the risk of hemorrhage should contribute to the overall benefit of selected ischemic stroke patients treated with rt-PA and with other PAs. This experience may also provide a clinical basis for the prospective study of antiplatelet agents and anticoagulants in acute ischemic stroke.     

Medical management of patients with an acute stroke: treatment and prevention

Stroke is a common and serious disorder and will probably occur with increasing frequency due to an aging of the population. Acute therapies aimed at reversing the effects of acute ischemic stroke are limited to recombinant tissue plasminogen activator administered intravenously within 3 hours of stroke onset. Neuroprotective agents and acute anticoagulation with agents such as heparinoids and heparin are not effective in most cases. Poststroke medical complications such as infection and venous thromboembolism are common but are largely preventable. A variety of medical therapies such as antiplatelet agents, warfarin, statins, and ACE inhibitors can reduce the risk of a recurrent stroke. A key aspect of management for stroke is selection of the proper treatment regimen for each patient.     

Blood pressure and lipid lowering in the prevention of stroke: a note to neurologists

Stroke is the leading cause of adult disability and dependency in western society. Despite the determined efforts of basic science and clinical investigators, neuroprotective therapies for acute stroke have yet to be realised. Stroke prevention, therefore, remains the key route for reducing morbidity and mortality. Hypertension and hypercholesterolaemia are the most important modifiable risk factors for stroke. Several recent landmark studies have shown that lipid lowering with statins can reduce the risk of ischaemic stroke, as well as coronary heart disease. In addition, clinical trials evaluating the effects of blood pressure lowering have shown that antihypertensive agents such as angiotensin-converting enzyme (ACE) inhibitors, calcium channel blockers (CCBs) and angiotensin II receptor antagonists can reduce stroke risk. Accumulating evidence suggests certain antihypertensive agents such as CCBs might also prevent the formation and progression of carotid atheroma, independently of their blood-pressure-lowering effects. It follows that rigorous identification and targeting of high- risk or stroke-prone individuals for blood pressure and lipid-lowering interventions should be of practical importance to all physicians involved in the management of stroke.     

Transient atrial fibrillation and risk of stroke after acute myocardial infarction

Atrial fibrillation (AF) is a frequent complication of acute myocardial infarction (AMI). In the AMI setting, AF is frequently brief and attributed to acute haemodynamic changes, inflammation or ischaemia. However, it remains uncertain whether transient AF episodes are associated with a subsequent increased risk of ischaemic stroke. We studied the impact of transient new-onset AF on the one-year risk of ischaemic stroke or transient ischaemic attack (TIA) in a retrospective cohort of 2,402 patients with AMI. Patients with previous AF or AF at hospital discharge were excluded. Transient AF occurred in 174 patients (7.2%) during the initial hospitalisation. During one year follow-up after hospital discharge, stroke or TIA occurred in 16 (9.2%) and 58 (2.6%) patients with and without transient AF, respectively (p< 0.0001). Compared with patients without transient AF, the adjusted hazard ratio for stroke or TIA in patients with transient AF was 3.03 (95% CI 1.73-5.32; p< 0.0001). Stroke or TIA occurred in 2.6% of patients without AF, 6.3% of patients with transient AF treated with oral anticoagulants, and 9.9% of patients with transient AF treated with antiplatelet agents. The incidence of recurrent AF after hospital discharge was markedly higher in patients with transient AF during the index hospitalisation (22.8% vs. 2.0%, p< 0.0001). In conclusion, transient AF complicating AMI is associated with an increased future risk of ischaemic stroke and TIA, particularly in patients treated with antiplatelet agents alone. High AF recurrence rates in these patients also suggest that oral anticoagulants should be strongly considered.     

缺血性卒中患者二级预防相关脑微出血形成的危险因素分析

目的 探讨缺血性卒中患者二级预防时脑微出血(CMBs)形成的危险因素,为脑血管病的防治提供依据和指导.方法 收集明确诊断为急性缺血性卒中的患者,且在应用抗血小板聚集药物治疗4 d内完成磁敏感加权成像(SWI)检查,对纳入的患者随访12个月,12个月后复查SWI,记录随访前后CMBs的数量和部位.结果 共纳入了94例患者,其中发现伴CMBs患者50(53.2%)例,经二分类Logistics回归分析发现:高血压病史(OR=1.2,95%CI=1.07~1.61,P=0.004)、年龄(OR=2.2,95%CI=1.25~3.92,P=0.006)是CMBs形成的独立危险因素,且年龄每增加10岁,CMBs患病率增加2.2倍,经ROC曲线分析发现:年龄曲线下面积为0.695(95%CI=0.588~0.802),年龄预测CMBs的最佳cutoff值为62岁,当患者年龄≥62岁时,发生CMBs的风险明显增高.在12个月的随访中有22例患者复查SWI检查,发现新增CMBs病灶33个,经Wilcoxon非参数配对秩和检验结果显示随访后CMBs数量的中位数是2.5个,基线时是1个(Z=-3.1,P=0.002),随访前后CMBs数量差异有统计学意义.结论 对于年龄≥62岁、高血压病史、规律应用抗血小板聚集药物的缺血性卒中患者,应定期监测CMBs的数量和部位,以指导二级预防治疗方案.     

Treatment of arterial ischemic stroke in children

Stroke is a rare but increasingly recognized disorder in children. Current therapies for arterial ischemic stroke include thrombolytic, antithrombotic and antiplatelet agents, blood transfusion and surgery. Adult studies, pediatric case studies and expert opinion form the basis for these treatment strategies. Thrombolytic agents are increasingly used but, as in adults, the majority of arterial ischemic strokes in children are treated with antiplatelet and antithrombotic agents. Sickle-cell patients, a distinct subset of the pediatric stroke population, are treated primarily with transfusion therapy. Pediatric arterial ischemic stroke studies are needed to determine the most appropriate course of treatment. An international study is currently in progress to formally study the incidence, risk factors, treatment strategies and outcomes of stroke in children.     

Recurrent stroke/TIA in cryptogenic stroke patients with patent foramen ovale

BACKGROUND: Patent foramen ovale (PFO) is present in 40% of patients with cryptogenic stroke and may be associated with paradoxical emboli to the brain. Therapeutic options include antiplatelet agents, anticoagulation, percutaneous device and surgical closure. We assessed the hypothesis that there are differences in rates of recurrent TIA or stroke between patients in the four treatment groups. METHODS: Patients presenting from January 1997 with cryptogenic stroke or TIA and PFO were followed prospectively until June 2003. Treatment choice was made on an individual case basis. The primary outcome was recurrent stroke. The secondary outcome was a composite of stroke, TIA, and vascular death. RESULTS: Baseline. Our cohort consisted of 121 patients; 64 (53%) were men. Median age was 43 years. Sixty-nine percent presented with stroke and 31% with TIA. One or more vascular risk factor was present in 40%. Atrial septal aneurysm (ASA) was present in 24%. Treatment consisted of antiplatelet agents (34%), anticoagulation (17%), device (39%) and surgical closure (11%). Follow-up. Recurrent events occurred in 16 patients (9 antiplatelet, 3 anticoagulation, 4 device closure); 7 were strokes, 9 were TIA. Comparing individual treatments there was a trend toward more strokes in the antiplatelet arm (p = 0.072); a significant difference was seen for the composite endpoint (p = 0.012). Comparing closure versus combined medical therapy groups, a significant difference was seen for primary (p = 0.014) and secondary (p = 0.008) outcomes, favoring closure. Age and pre-study event predicted outcome. CONCLUSION: Patent foramen ovale closure was associated with fewer recurrent events. Complications of surgical and device closure were self-limited.