Fibrinolytic therapy in acute stroke

Acute ischemic stroke is a major cause of morbidity and mortality in Europe, North America, and Asia. Its treatment has completely changed over the past decade with different interventional approaches, such as intravenous trials, intra-arterial trials, combined intravenous/intra-arterial trials, and newer devices to mechanically remove the clot from intracranial arteries. Intravenous thrombolysis with tissue plaminogen activator (tPA) within 4.5 hours of symptoms onset significantly improved clinical outcomes in patients with acute ischemic stroke. Pharmacological intra-arterial thrombolysis has been shown effective until 6 hours after middle cerebral artery occlusion and offers a higher rate of recanalization compared with intravenous thrombolysis, whereas combined intravenous/ intra-arterial thrombolysis seems to be as safe as isolated intravenous thrombolysis. The more recent advances in reperfusion therapies have been done in mechanical embolus disruption or removal. Merci Retriever and Penumbra System have been approved for clot removal in brain arteries, but not as a therapeutic modality for acute ischemic stroke since it is no clear whether mechanical thrombectomy improves clinical outcome in acute stroke. However, mechanical devices are being used in clinical practice for patients who are ineligible for tPA or who have failed to respond to intravenous tPA. We summarize the results of the major thrombolytic trials and the latest neurointerventional approaches to ischemic stroke.     

Minimising time to treatment: targeted strategies to minimise time to thrombolysis for acute ischaemic stroke

Time to thrombolysis is a critical determinant of favourable outcomes in acute ischaemic stroke. It is not infrequent that patient outcomes are compromised due to out‐of‐hospital and in‐hospital time delays. On the other hand, time delays could be minimised through the identification of barriers and the implementation of targeted solutions. This review outlines the different strategies in minimising treatment delays and offers recommendations. Literature search in PubMed, Medline and EBSCO Host was conducted to identify studies that are relevant to reduction of time to treatment from January 1995 to December 2012. Strategies to reduce time to thrombolysis are categorised into pre‐hospital strategies, in‐hospital strategies and post‐treatment decision strategies. Proposed pre‐hospital strategies include public education on stroke symptoms awareness, prioritising stroke by emergency medical services, increasing ease of access to medical records, pre‐hospital notification, and mobile computed tomography scanning. In‐hospital strategies include a streamlined code stroke system, computed tomography scanner co‐location with emergency department, 24/7 availability of stroke physicians, point‐of‐care laboratory testing and access to expert neuroimaging interpretation. Post‐decision strategies include increasing availability of intravenous thrombolysis and simplification of informed consent procurement. Time to thrombolysis delays is multifactorial. Effective reduction of time delays for acute ischaemic stroke requires the correct identification of and targeted strategies to overcome time barriers.     

伴心房颤动的急性缺血性卒中的治疗

心房颤动是缺血性卒中的一种重要病因.研究表明,与无心房颤动者相比,伴有心房颤动的卒中患者会出现更严重的神经功能缺损和更高的病死率.此外,心房颤动还是静脉溶栓后血管未能再通的独立危险因素,与转归不良相关.机械取栓治疗为伴有心房颤动的急性缺血性卒中患者提供了新的治疗方案.文章就合并心房颤动的急性缺血性卒中患者的静脉溶栓和机械取栓治疗进行了综述.     

Current and future recanalization strategies for acute ischemic stroke

Abstract. Alexandrov AV (University of Alabama Hospital, Birmingham, AL, USA). Current and future recanalization strategies for acute ischemic stroke (Review). J Intern Med 2010; 267: 209–219. In a quest for stroke treatment, reperfusion proved to be the first key to the puzzle. Systemic tissue plasminogen activator (tPA), the first and currently the only approved treatment, is also the fastest way to initiate thrombolyis for acute ischemic stroke. tPA works by induction of mostly partial recanalization since stroke patients often have large thrombus burden. Thus, early augmentation of fibrinolysis and multi‐modal approach to improve recanalization are desirable. This review focuses on the following strategies available to clinicians now or being tested in clinical trials: (a) faster initiation of tPA infusion; (b) sonothrombolysis; (c) intra‐arterial revascularization, bridging intravenous and intra‐arterial thrombolysis, mechanical thrombectomy and aspiration; and (d) novel experimental approaches. Despite these technological advances, no single strategy was yet proven to be a ‘silver bullet’ solution to reverse acute ischemic stroke. Better outcomes are expected with faster treatment leading to early, at times just partial flow improvement rather than achieving complete recanalization with lengthy procedures. Arterial re‐occlusion can occur with any of these approaches, and it remains a challenge since it leads to poor outcomes and no clinical trial data are available yet to determine safe strategies to prevent or reverse re‐occlusion.     

No space left for intravenous thrombolysis in acute stroke: CONS

Recent successful clinical trials of endovascular thrombectomy for large artery ischaemic stroke have established the value of this treatment modality as an adjunct to intravenous thrombolysis, not as an alternative: thrombectomy delivery was undertaken in the context of highly efficient networks for acute thrombolysis delivery and the great majority of patients received IV thrombolytic drug treatment. Even for the minority of acute stroke patients for whom thrombectomy is potentially relevant, access will be limited by geography and service infrastructure. Developments in intravenous thrombolysis in the near future will likely produce safer and more effective intravenous treatments. Intravenous thrombolysis will remain the first line of treatment for the great majority of acute stroke patients.     

DRAGON评分对颅内大血管闭塞致急性缺血性卒中静脉溶栓桥接机械取栓临床结局的预测作用

目的评估前循环颅内大血管闭塞致急性缺血性卒中患者入院时DRAGON[dense cerebral artery,mRS(改良Rankin量表),age,glucose level,onset to treatment time,NIHSS(美国国立卫生研究院卒中量表)]评分对静脉溶栓桥接机械取栓术后患者临床结局的预测作用。方法回顾性连续纳入2015年1—12月急性缺血性卒中血管内治疗试验(EAST)中接受机械取栓及静脉溶栓桥接机械取栓治疗的急性缺血性卒中患者149例,为发病至治疗时间≤6 h,于术前经CT血管成像和(或)MR血管成像和(或)DSA证实。根据治疗后90 d mRS评分,将149例患者分为预后良好(mRS评分0~2分)组和预后不良(mRS评分3~6分)组。收集并比较两组患者的人口学资料、脑血管病危险因素(高血压病、糖尿病、心房颤动等)、入院时NIHSS评分、发病时间、卒中前mRS评分、影像学特征、实验室检查、DRAGON评分、治疗方式的差异。对静脉溶栓桥接机械取栓不同预后者上述指标进行比较,并采用受试者工作特征(ROC)曲线确定DRAGON预测静脉溶栓桥接机械取栓患者预后的最佳截断值。结果(1)预后良好组患者基线NIHSS评分低于预后不良组[14(11,18)分比18(14,21)分],男性比例高于预后不良组[71.1%(59/83)比50.0%(33/66)],组间差异均有统计学意义(均P<0.01);两组年龄、高血压病、糖尿病、心房颤动、高脂血症、卒中史、高密度征、早期脑梗死征象的差异均无统计学意义(均P>0.05)。(2)预后良好组血糖水平及基线DARGON评分均低于预后不良组,组间差异均有统计学意义[(6.5±1.5)mmol/L比(8.2±3.3)mmol/L,(4.4±1.3)分比(5.2±1.4)分;均P<0.01];两组发病至治疗时间、发病至再通时间、血肌酐、白细胞计数、卒中前mRS 0~1分比例及静脉溶栓桥接机械取栓比例的差异均无统计学意义(均P>0.05)。(3)静脉溶栓桥接机械取栓术后预后良好者基线NIHSS评分、发病至治疗时间、发病至成功再通时间、血糖水平、基线DARGON评分均低于预后不良者,二者差异均有统计学意义[14(10,16)分比19(16,24)分,168(126,134)min比239(210,295)min,199(183,285)min比275(260,345)min,(6.4±1.2)mmol/L比(9.0±2.4)mmol/L,(4.3±1.5)分比(6.1±1.2)分;均P<0.05];二者间其余基线和临床资料的差异均无统计学意义(均P>0.05)。(4)基线DRAGON评分预测静脉溶栓桥接机械取栓术后90 d预后的ROC曲线下面积为0.830,最佳截断值为6分,其敏感度为63.6%,特异度为91.7%。结论入院时DRAGON评分可能对前循环大血管闭塞致急性缺血性卒中患者接受静脉溶栓桥接机械取栓后的预后具有一定的预测作用。     

Acute myocardial infarction and acute stroke: What are the differences? Focus on reperfusion therapy

This review compares acute myocardial infarction and acute stroke— their similarities and differences. The focus is given on reperfusion therapy: pharmacologic, mechanical or combined. The key trials and metaanalyses are described.The published data on iv. thrombolysis show, that even among a subgroup of patients treated within 90 min from stroke onset the trend to lower mortality is not significant and in all other subgroups (i.e. treated after >90 min) there is a trend towards increased mortality with thrombolytic treatment.The data on combined therapy demonstrate, that there is no benefit from facilitated intervention (iv. thrombolysis followed by ia. thrombolysis ± catheter intervention) over iv. thrombolysis alone in acute stroke. This is very similar to the situation in acute myocardial infarction 25 years ago (intracoronary thrombolysis was not superior to intravenous thrombolysis) or more recently (facilitated PCI was not shown to be superior in several trials).The latest generation of stent retrievers is able to recanalize >70% of occluded intracranial arteries—approximately twice more compared to thrombolysis. However, it is not yet known whether this translates to better clinical outcomes. The sufficient data on clinical outcomes after primary catheter-based thrombectomy (without thrombolysis) are still missing and trials comparing iv. thrombolysis versus primary catheter-based thrombectomy are urgently needed.The future trials in acute stroke may follow the way paved by acute myocardial infarction trials. If such trials would demonstrate superiority of catheter-based thrombectomy, we can face in future similar revolution in acute stroke treatment as we have been facing in acute MI treatment in the past years.     

机械取栓装置在缺血性卒中患者治疗中的应用

目前,在发病4．5h内进行静脉溶栓仍然是治疗急性缺血性卒中患者的最有效方法。对于不符合静脉溶栓治疗标准、静脉溶栓后症状无明显改善甚至恶化的患者,血管内介入治疗是一种安全的替代治疗方法。经动脉机械取栓装置能实现迅速和完全的血管再通,为急性缺血性卒中患者提供了更多的治疗选择。文章对近年来机械取栓装置相关的技术演变和临床试验进行了综述。     

Reperfusion Therapies for Acute Ischemic Stroke: An Update

Acute ischemic stroke is a major cause of morbidity and mortality in developed countries. Intravenous thrombolysis with tissue plasminogen activator (tPA) within 4.5 hours of symptoms onset significantly improves clinical outcomes in patients with acute ischemic stroke. This narrow window for treatment leads to a small proportion of eligible patients to be treated. Intravenous or intra-arterial trials, combined intravenous/intra-arterial trials, and newer devices to mechanically remove the clot from intracranial arteries have been investigated or are currently being explored to increase patient eligibility and to improve arterial recanalization and clinical outcome. New retrievable stent-based devices offer higher revascularization rates with shorter time to recanalization and are now generally preferred to first generation thrombectomy devices such as Merci Retriever or Penumbra System. These devices have been shown to be effective for opening up occluded vessels in the brain but its efficacy for improving outcomes in patients with acute stroke has not yet been demonstrated in a randomized clinical trial. We summarize the results of the major systemic thrombolytic trials and the latest trials employing different endovascular approaches to ischemic stroke.     

Periprocedural antithrombotic medication in acute ischemic stroke treated by catheter-based thrombectomy. A review

This review summarized limited information known about periprocedural antithrombotic therapy before, during and immediately after percutaneous catheter-based thrombectomy for acute ischemic stroke. Very few data on this topic were published so far. In general, rtPA should be used upfront whenever clinically clearly indicated (0–3 h from stroke onset, absence of contraindications) irrespective of subsequent mechanical thrombectomy. If mechanical treatment follows after thrombolysis, neither anticoagulation, nor antiplatelet agents should be used in the acute phase. No data exist about the periprocedural use of anticoagulation or antiplatelet therapy in patients who cannot receive fibrinolysis and undergo direct mechanical thrombectomy alone. Most centers use no or very low dose heparin and a single dose of aspirin.     

Two cases of successful recanalization for acute cerebral artery embolism during perioperative period of radiofrequency ablation for atrial fibrillation

To explore the strategy of acute cerebral artery embolism after radiofrequency catheter ablation (RFA) for atrial fibrillation (AF). Reporting two cases with acute cerebral infarction after RFA for AF. Two patients were both with AF, and intracardiac thrombus was excluded through transesophageal echocardiogram (TEE) before procedure. Approach of ablation: circumferential pulmonary vein ablation in left atrium to isolate pulmonary vein plus linear ablation in the top and bottom of left atrium (BOX procedure). They both received Dabigatran Etexilate 110 mg twice daily, starting 6 hr after ablation. Symptoms of major stroke appeared 30 hr after ablation in Case 1. Occlusion was detected in M1 segment of the left middle cerebral artery by MRI 2 hr after symptoms onset. Intravenous thrombolysis was given immediately. In Case 2, the patient presented symptoms of major stroke 34 hr after ablation and occlusion in the basilar artery was confirmed by MRI 4.5 hr after symptoms onset. Although it was beyond the thrombolysis time window, mechanical thrombectomy was taken 7 hr after the symptoms onset. The culprit artery was successfully revascularized in both cases. In Case 1, NIHSS score was reduced from 8 (before thrombolysis) to 0 (24 hr after thrombolysis). In Case 2, NIHSS score decreased from 18 (before embolectomy) to 3 (24 hr after embolectomy). Both of the patients live a normal life without brain function impairment and hemorrhage until the last follow‐up. Timely recanalization could attained a good cure effect when acute stoke was happened after RFA for AF.     

静脉溶栓桥接治疗急性缺血性卒中

静脉溶栓是治疗急性缺血性卒中的首选方法,但在大血管闭塞性卒中患者中的血管再通率较低.以血管内机械血栓切除术为代表的血管内治疗能有效使缺血性卒中患者闭塞血管再通和改善转归.文章对静脉溶栓桥接治疗的现状和发展方向进行了综述.     

Catheter‐based therapy for acute ischemic stroke: A national unmet need

Early reperfusion therapy for acute stroke, similar to acute myocardial infarction, has the best opportunity to reduce morbidity and mortality. Treatment options include intravenous (IV) thrombolysis therapy and/or catheter‐based therapy (CBT). Catheter‐based therapies include local intra‐arterial thrombolysis, mechanical thrombectomy, and angioplasty techniques. Intravenous thrombolysis is limited to the first three hours after symptom onset, which excludes many patients with disabling stroke deficits. Catheter‐based therapy is effective up to seven hours after onset, but availability is limited by the lack of neurointerventionalists available around the clock to provide this care. To increase the number of providers for acute stroke reperfusion therapy, we have formed a multidisciplinary team to take advantage of cardiologists' carotid stent placement experience to provide continuous coverage for emergency reperfusion therapy. We present two cases of acute stroke treated with CBT by interventional cardiologists. © 2008 Wiley‐Liss, Inc.     

Stroke. Diagnosis and therapeutic management of cerebrovascular disease

Stroke is the second cause of death and the first cause of disability with an important economical cost. Thrombolysis and stroke units are the major contribution to stroke treatment of the last years changing a nihilist therapeutic attitude towards an active attitude, stroke is a medical emergency. Treatment with rtPA has shown to be effective in the first 3 hours following stroke and the FDA and the European Medical Agency (EMEA) have approved its use. A protocolised management of the acute phase to treat physiological complications is the mainstone of stroke units showing a reduction in mortality and disability. Multiple strategies are under development in order to treat more patients, drugs with a longer therapeutic window, intravenous thrombolysis followed by intrarterial thrombolysis, selection of patients with mismatch with new neuroimaging techniques and neuroprotective therapies. Preventive treatment has also experienced a change due to a better knowledge of the ethiopathogeny, the role of vascular risk factors and the development of new preventive drugs. Knowledge of cerebrovascular diseases is today's clue for the best treatment of our patients.     

动脉溶栓和动静脉联合溶栓及机械取栓治疗急性脑梗死的比较研究

目的评价动脉溶栓、动静脉联合溶栓和单纯机械取栓治疗急性脑梗死的疗效及安全性。方法选择急性脑梗死颅内血管狭窄或闭塞患者61例,根据不同溶栓方法分动脉溶栓组25例,动静脉联合溶栓组(联合溶栓组)17例,单纯机械取栓组(机械取栓组)19例。分别对治疗前后患者的美国国立卫生研究院卒中量表(NIHSS)评分、治疗的有效性、近期与远期疗效进行分析。结果与治疗前比较,动脉溶栓组、联合溶栓组治疗后2周NIHSS评分明显降低(P<0.05,P<0.01),机械取栓组治疗后3d、2周NIHSS评分明显降低(P<0.05,P<0.01)。动脉溶栓组残余狭窄率≤30%发生率、急性血管再闭塞率和病死率分别为16.0%、52.0%和12.0%,联合溶栓组分别为11.8%、52.9%和0,机械取栓组分别为47.4%、0和10.5%。3组残余狭窄率≤30%发生率、急性血管再闭塞率比较,差异有统计学意义(P<0.05,P<0.01)。结论不论采用动脉溶栓、动静脉联合溶栓还是机械取栓方法,均可使患者神经功能改善,对近期临床预后的改善有相近效果。采用机械取栓方法对神经功能改善时间较早、溶栓效果、安全性及远期临床预后较好。     

Management of Acute Ischemic Stroke

The treatment of acute ischemic stroke includes both intravenous (IV) thrombolysis and mechanical thrombectomy. Important advances regarding both treatment modalities have occurred recently that all physicians who see patients at risk for or who have had a stroke should be aware of. This review will focus on recent clinical trials of IV thrombolysis both positive and negative. Additionally, the results of a large number of early and late time window thrombectomy trials will be presented that demonstrate the remarkable efficacy of this treatment for appropriately selected patients.     

Management of acute ischaemic stroke in patients with dementia

An estimated 10% of stroke patients have an underlying dementia. As a consequence, health professionals often face the challenge of managing patients with dementia presenting with an acute stroke. Patients with dementia are less likely to receive thrombolysis (0.56–10% vs. 1–16% thrombolysis rates in the general population), be admitted to a stroke unit or receive some types of care. Anticoagulation for secondary stroke prevention is sometimes withheld, despite dementia not being listed as an exclusion criterion in current guidelines. Studies in this population are scarce, and results have been contradictory. Three observational studies have examined intravenous thrombolysis for treatment of acute ischaemic stroke in patients with dementia. In the two largest matched case–control studies, there were no significant differences between patients with and without dementia in the risks of intracerebral haemorrhage or mortality. The risk of intracerebral haemorrhage ranged between 14% and 19% for patients with dementia. Studies of other interventions for stroke are lacking for this population. Patients with dementia are less likely to be discharged home compared with controls (19% vs. 41%) and more likely to be disabled (64% vs. 59%) or die during hospitalization (22% vs. 11%). The aim of this review was to summarize current knowledge about the management of ischaemic stroke in patients with pre‐existing dementia, including organizational aspects of stroke care, intravenous thrombolysis, access to stroke unit care and use of supportive treatment. Evidence to support anticoagulation for secondary prevention of stroke in patients with atrial fibrillation and antiplatelet therapy in nonembolic stroke will be discussed, as well as rehabilitation and how these factors influence patient outcomes. Finally, ethical issues, knowledge gaps and pathways for future research will be considered.     

优化急性缺血性脑卒中静脉溶栓绿色通道流程

目的 探讨优化急性缺血性脑卒中患者静脉溶栓绿色通道流程的效果.方法 选取我院收治的140例急性缺血性脑卒中患者为研究对象,2018年1月至8月本科室收治的静脉溶栓患者70例为对照组,2019年5月至12月优化急性缺血性脑卒中静脉溶栓绿色通道治疗流程后收治的患者70例为观察组.比较两组患者急诊至抽血检验时间、急诊至CT完...     

No space left for intravenous thrombolysis in acute stroke: PROS

Five recently published RCTs (MR CLEAN, EXTEND-IA, SWIFT PRIME, REVASCAT and ESCAPE) employing mechanical thrombectomy with modern stent retriever devices clearly demonstrated the superiority of endovascular treatment compared to thrombolysis alone, which is now considered standard first-line therapy for selected patients with acute severe ischemic stroke and large vessel in the anterior circulation. RCT results led to recommendations outlined in “Mechanical thrombectomy in acute ischemic stroke by ESO-Karolinska Stroke Update 2014/2015, supported by ESO, ESMINT, ESNR and EAN”. Moreover, endovascular procedures in the 5 RCTs to date were performed at high-volume referral centers with, in some trials, rigid requirements for the interventionalist to participate, which may have contributed substantially to the excellent results, supporting the concept of centralization of intra-arterial thrombolysis resources and expertise. Therefore, patients with suspected large-artery occlusion and deemed candidates for thrombectomy, should be treated at a Comprehensive Stroke Centre with 24/7 endovascular treatment services. There seems to be limited space left for intravenous thrombolysis alone in acute stroke patients with large-vessel occlusions as thrombectomy plus thrombolysis continues to be reported as being superior with regard to outcome.     

Diabetes hyperglycemia and recovery from stroke

Strokeis a major cause of death and severe disability in older people. Despite the burden of disease, there is still no safe, simple and proven medical therapy for the treatment of acute stroke. Advances in acute stroke treatment have been either consistently disappointing (neuroprotective therapy) or fraught with controversy regarding risk/benefit (thrombolysis), and attention is once again being directed towards physiological variables that may influence outcome. Both insulin-dependent and non-insulin-dependent diabetes mellitus are major risk factors for stroke. Diabetes mellitus has also been shown to be associated with increased mortality and reduced functional outcome after stroke. Hyperglycemia is a frequent finding following stroke and may reflect the metabolic stress of the acute event, so-called stress hyperglycemia, and/or underlying impaired glucose metabolism. Several large clinical studies have now demonstrated a positive association between a raised blood glucose and poor outcome from stroke; greater mortality and reduced functional recovery. What is not clear is to what extent hyperglycemia is a 'normal' physiological response to stroke or whether hyperglycemia per se increases cerebral damage in the acute phase. There are many potential mechanisms by which hyperglycemia can exert a harmful effect upon cerebral tissue and it is probable that an important relationship exists, not only between glucose and stroke outcome, but also between insulin and neuroprotection. It remains to be determined whether lowering and maintaining 'normal' glucose levels in the immediate aftermath of stroke, combined with the administration of insulin as an acute treatment, can modify this outcome.