Acute stroke intervention by interventional cardiologists

Objectives:

To report the technical success and clinical outcomes of catheter‐based therapy (CBT) for acute ischemic stroke in patients ineligible for intravenous thrombolysis.

Background:

Acute ischemic stroke is common but undertreated. CBT for acute ischemic stroke is a therapeutic option in selected patients who are not candidates for intravenous thrombolysis.

Methods:

Consecutive stroke patients who were ineligible for intravenous thrombolysis and underwent CBT were identified by retrospective chart review. Demographic information, National Institutes of Health Stroke Scale (NIHSS), procedural characteristics, and clinical outcomes during hospitalization and at 90 days follow up were collected. Experienced interventional cardiologists with the consultative support of stroke neurologists were on call for acute strokes.

Results:

A total of 33 acute ischemic stroke patients underwent emergency cerebral angiography, with 26 patients undergoing CBT. Successful “culprit” artery recanalization was achieved in 23 (88%) of the 26 patients. In‐hospital adverse events occurred in 4 (15%) patients, with intracerebral hemorrhage (ICH) (12%) representing the most common adverse event. The baseline NIHSS for patients who underwent intervention was 16.5 ± 9.9 (median 16) and improved significantly to 9.9 ± 8.7 (median 9) (P < 0.001) at hospital discharge. A modified Rankin score of two or less (indicating mild disability) was achieved in half (n = 13) of the CBT treated patients. All cause mortality at 90 days was 8% (2/26).

Conclusions:

In selected patients, CBT provided by qualified interventional cardiologists supported by stroke neurologists, offers a safe and effective option for patients with acute stroke who are not eligible for intravenous thrombolysis. © 2008 Wiley‐Liss, Inc.     

急性缺血性卒中的溶栓治疗进展

重组组织型纤溶酶原激活剂静脉溶栓是目前惟一一种证实有效的治疗急性缺血性卒中的药物。在许多情况下,费用低廉的尿激酶不失为一种较好的选择。虽然溶栓治疗日趋成熟,但一些问题仍需进一步探讨,如新的溶栓药物用于发病3h以上的急性缺血性卒中患者、评价各种新的再灌注方法、静脉和动脉内药物溶栓联合应用、溶栓和新型抗小板药的联合应用,以及应用机械装置或经颅多普勒超声促进药物溶栓的作用等等。     

Acute Stroke Intervention

Ischemic strokes will make up most (>80%) of the three-quarters of a million strokes that will occur in Americans this year. Reperfusion therapy is the fundamental strategy for the treatment of acute ischemic stroke. Reperfusion therapy may be accomplished noninvasively (intravenous thrombolysis) or invasively with catheter-based treatments (intra-arterial thrombolysis, thrombectomy, or angioplasty). Currently, a large majority of patients with acute ischemic stroke do not receive any form of reperfusion therapy owing to their delayed presentation (>3 hours) and lack of skilled man power for on-demand endovascular treatment. Paradoxically, improved success rates for reperfusion have been reported with the newer thrombectomy catheters, called “stentreivers.” An option for broadening access for patients who need endovascular therapy would be to use interventional cardiologists with carotid stent experience who can help to provide 24×7×365 coverage.     

Innovative strategies in the management of acute stroke

Advances in acute stroke therapy are rapidly changing our approach to management of patients with ischemic stroke. Intravenous tissue-plasminogen activator (tPA) was the first treatment demonstrated in a randomized controlled trial to improve outcome if given within the first 3 hours of stroke onset. Subsequent trials failed to extend the time window for intravenous therapy beyond 3 hours. Intra-arterial thrombolysis provides an alternative approach, with several advantages over intravenous therapy. The major drawback is the additional time needed for the interventional procedure, and the equipment and personnel requirements. New strategies aimed at reducing the total time from stroke onset to recanalization of occluded arteries include a combined intravenous/ intra-arterial delivery of thrombolysis and mechanical devices. For the millions of stroke survivors, investigations are now underway into the possibility of improvement of function through neuronal transplantation.     

Innovative Strategies in the Management of Acute Stroke

Opinion statement Advances in acute stroke therapy are rapidly changing our approach to the management of patients with ischemic stroke. Intravenous tissue plasminogen activator was the first treatment demonstrated in a randomized controlled trial to improve outcome if given within the first 3 hours of stroke onset. Subsequent trials failed to extend the time window for intravenous therapy beyond 3 hours. Intraarterial thrombolysis provides an alternative approach, with several advantages over intravenous therapy. The major drawback is the additional time needed for the interventional procedure, and the equipment and personnel requirements. New strategies aimed at reducing the total time from stroke onset to recanalization of occluded arteries include a combined intravenous/intra-arterial delivery of thrombolysis and mechanical devices. For the millions of stroke survivors, investigations are now underway into the possibility of improvement of function through neuronal transplantation.     

Efficacy of coronary angioplasty following conventional coronary thrombolysis in patients with acute myocardial infarction

The efficacy of combined thrombolysis and angioplasty for the purpose of coronary reperfusion after acute myocardial infarction has been controversial. The present study was conducted, therefore, to evaluate the effects of angioplasty following administration of conventional thrombolytic agents on the long-term prognosis of acute myocardial infarction patients. A total of 409 patients admitted to the hospital within 12 hours of the onset of infarction between January 1990 and May 2001 were studied retrospectively. These included 151 patients treated with thrombolysis alone (group T), 73 patients treated with angioplasty alone (group A), and 35 patients treated with angioplasty after thrombolysis (group T&A). Group T&A had shorter intervals from onset to initial treatment than group A (3.0 hours vs 6.3 hours, p < 0.01), a higher reperfusion success rate than group T (91.4% vs 74.8%, p < 0.01), and more improved left ventricular wall motion than group A. One-year cardiac mortality rates tended to be higher in group T, which had a higher rate of unsuccessful reperfusion than groups T&A or A (8.1% vs 3.4% vs 3.5%). The frequencies of hemorrhagic complications were similar among the 3 groups. From these findings, we conclude that thrombolytic therapy with subsequent angioplasty is an effective strategy for achieving cardiac reperfusion following acute myocardial infarction.     

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.     

Reperfusion strategies in acute ST-elevation myocardial infarction: an overview of current status

Several randomized trials and meta-analyses have shown that primary angioplasty is superior to thrombolysis in the treatment of ST-segment elevation myocardial infarction (MI) in terms of death, reinfarction, and stroke. However, primary angioplasty should be regarded as the preferred strategy as long as it can not be applied with a reasonable time delay to treatment, as compared with the administration of thrombolysis. In fact, time-to-treatment has been shown to be a determinant of survival not only for thrombolysis but also for primary angioplasty. Recent guidelines consider a time from first medical contact to PCI of 90 minutes or a PCI-related delay of 60 minutes as reasonable cutoffs to identify the best reperfusion strategy. The beneficial effects of primary angioplasty could be expected particularly after the first 3 hours from symptom onset, when thrombolysis, particularly streptokinase, may be less effective, whereas within the first 3 hours, thrombolysis (started in the prehospital setting, preferably) may represent a valid therapeutic option. Because the survival benefits of primary angioplasty depends on the patient's risk profile and timely application of reperfusion, we would suggest, among patients in the first hours from symptom onset, a strategy of early pharmacologic reperfusion and transfer to primary PCI centers, where the decision of performing angiography acutely may be based on the assessment of myocardial reperfusion and risk profile, whereas after the first 3 hours from symptoms onset, primary angioplasty should be considered the preferred strategy if applicable, particularly in regions when streptokinase still represents the only available lytic therapy. However, even though primary angioplasty is able to achieve thrombolysis and TIMI 3 flow in most patients, a still relevant proportion of patients experience poor myocardial reperfusion, with negative impact on acute and long-term survival. The use of platelet glycoprotein IIb/IIIa complex inhibitors has significantly improved survival, with additional benefits obtained by early administration aiming at early reperfusion, which are to be recommended, particularly among high-risk patients and those presenting within the first hours from symptom onset. The use of adjunctive mechanical devices has reduced the incidence of distal embolization without any apparent benefit in survival. Until the results of larger randomized trials become available, these devices may be considered in patients at high risk for distal embolization, such as those with large thrombotic burden. The use of coronary stenting has significantly reduced restenosis, as compared with balloon angioplasty. Several randomized trials have recently been conducted on drug-eluting stents in ST-segment elevation MI, showing the safety and significant benefits of these devices in terms of restenosis, as compared with bare metal stents (BMSs). However, because of unpredictable compliance to long-term double oral antiplatelet therapy in acute patients, caution should be taken with extensive use of drug-eluting stents in primary angioplasty.     

Combined reperfusion in patients with acute myocardial infarction

Three schemes of treatment were used in the management of 230 patients with acute myocardial infarction: immediate thrombolysis (group 1, n=71), immediate thrombolysis followed by angioplasty in 12 hours - 7 days depending of the clinical picture of the disease (group 2, n=65), primary angioplasty not later than 12 hours after onset of pain (group 3, n=94). Clopidogrel was given to all patients at least in 2 hours before primary angioplasty and no less than in 6 hours in combined reperfusion. Composite end point (total number of lethal outcomes and nonfatal reinfarctions) was significantly higher in group 1 (14.1%) compared with groups 2 (3.0%) and 3 (3.2%). Invasive intervention improved results of treatment after both effective and ineffective preceding thrombolytic therapy. Thus efficacy of combined reperfusion therapy is not inferior to primary angioplasty if interval between thrombolysis and invasive intervention varies between 12 hours and 7 days and angioplasty is carried out at the background of antiaggregant therapy with clopidogrel and aspirin.     

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.     

高龄脑梗死患者重组组织型纤溶酶原激活剂静脉溶栓的有效性和安全性

目的探讨高龄脑梗死患者应用重组组织型纤溶酶原激活剂(rt -PA)静脉溶栓治疗的有效性和安全性。方法选择急性脑梗死患者196例,根据患者年龄分为<80岁组141例和≥80岁组55例,发病<4.5 h的患者给予rt-PA静脉溶栓治疗,比较2组患者溶栓前、溶栓后14 d的美国国立卫生研究院卒中量表(NIHSS)评分,观察溶栓后颅内出血(ICH)和症状性颅内出血(sICH)的发生率。90 d随访时,采用改良Rankin's评分评定临床结局。结果 2组溶栓后14 d的NIHSS评分都较溶栓前显著降低(P<0.01),<80岁组较≥80岁组NIHSS评分降低更明显(P<0.01)。≥80岁组的病死率显著高于<80岁组(P<0.05);<80岁组和≥80岁组预后良好的比例分别为57.5%和45.5%(P>0.05),ICH发生率分别为16.3%和21.8%,sICH发生率分别为6.4%和14.5%(P>0.05)。结论高龄脑梗死患者应用rt-PA静脉溶栓和年龄<80岁者同样是安全有效的。     

急性脑梗死溶栓治疗的磁共振成像研究

目的探讨MRI对急性脑梗死溶栓后血管再通和梗死灶变化的评价。方法32例大脑前循环阻塞的急性脑梗死患者,其中20例行动脉内溶栓治疗(溶栓组),12例保守治疗(保守组)。治疗前后行MR常规T1加权成像、T2加权成像检查和磁共振血管成像(MRA)以及治疗前弥散加权成像、灌注加权成像检查。比较治疗前后MRA显示的血管再通和梗死灶变化情况。结果治疗前,MRA显示78%(25/32)血管阻塞。治疗后,溶栓组MRA显示72%(13/18)血管早期再通,而保守组中29%血管再通;两组有显著性差异(P=0.0279)。血管再通的病灶增加较小,与血管未通者比较差异有显著性意义(P<0.05)。结论MRI有助于急性脑梗死治疗后血管早期再通的显示及临床治疗效果的评价。     

Percutaneous transluminal coronary angioplasty for acute myocardial infarction

Studies have suggested that intracoronary and intravenous thrombolysis and emergency PTCA result in decreased infarct size, improved left ventricular function, and decreased in-hospital mortality. Significant problems remain with all three treatment modalities. Thrombolysis is associated with significant bleeding, especially if acute catheterization also is performed. The intracoronary method of thrombolysis requires cardiac catheterization facilities and entails a significant delay in reperfusion. Lower rates of reperfusion initially were found with intravenous than intracoronary streptokinase, but the intravenous administration of t-PA has been associated with a reperfusion rate (75 per cent) similar to that of intracoronary streptokinase. Significant bleeding complications occur with t-PA just as with streptokinase. Furthermore, there are patients in whom thrombolysis is contraindicated because of the high risk of life-threatening hemorrhagic complications. Once thrombolysis is achieved, an underlying significant coronary artery lesion usually is present so that a significant risk of recurrent ischemia and/or reinfarction still exists. In controlled studies, the addition of cardiac catheterization and angioplasty after thrombolytic therapy is associated with a further increase in significant bleeding episodes. Also, in low-risk subgroups of patients randomized to emergency angioplasty versus elective angioplasty or noninvasive treatment after thrombolytic therapy, the complications of angioplasty may outweigh the benefits of further reduction in lesion severity. Potential problems of emergency angioplasty following thrombolytic therapy include: (1) hemorrhage into ischemic myocardium, which may have a deleterious effect on ultimate muscle recovery; (2) hemorrhage at the angioplasty site caused by thrombolytic therapy, with a resultant increased chance of occlusion of the vessel post-angioplasty, and (3) production of reperfusion arrhythmias and hypotension, predisposing to vessel reclosure and infarct extension. With primary angioplasty therapy, the reperfusion success rate is 85 to 90 per cent. This is higher than the approximately 75 per cent success rate with thrombolytic therapy alone. If angioplasty can be performed expeditiously, within 6 hours of the onset of ischemia, potential advantages of this technique include: (1) rapid reperfusion, possibly comparable to thrombolytic therapy alone; (2) higher success rate for reperfusion than thrombolytic therapy; (3) alleviation of underlying stenosis usually present after thrombolytic therapy alone; (4) avoidance of systemic thrombolysis, with a concomitant decrease in hemorrhagic risk; (5) possible avoidance of hemorrhagic infarction, which may have a deleterious effect on ultimate muscle recovery; and (6) applicability to patients in cardiogenic shock, who presently respond poorly to thrombolytic therapy alone. No large controlled randomized study exists comparing primary angioplasty with thr     

急性缺血性卒中的溶栓治疗

急性缺血性卒中的溶栓治疗是目前医学研究的热点。近年来的研究表明,溶栓治疗的时间窗应个体化。新的影像学技术有助于判断缺血半暗带和选择适合溶栓的病例。溶栓治疗的方法包括静脉溶栓、动脉溶栓和动静脉联合溶栓。影响溶栓疗效的因素包括从发病到开始溶栓治疗的时间、患者基础状况、溶栓药和联合用药、入选和治疗标准的执行情况以及是否在卒中单元内监护。     

Treatment of acute ischemic stroke: recent progress

Intravenous thrombolysis with tissue plasminogen activator is currently the most effective treatment of acute ischemic stroke if administerd within 3 hours after symptom onset. Intraarterial thrombolysis by prourokinase is the another choise if the middle cerebral artery is occluded and within less than 6 hours after onset. Although heparin especially a moderate dose is not proved to be effective, a randomized, placebo-controlled trial to determine the safety and efficacy of argatroban (a selective thrombin inhibitor) in patients with acute ischemic stroke was started in USA. Aspirin provides some benefit to patients with acute stroke. However, its effect is not fully satisfactory. Although reports of numerous trials for neuroprotective drugs have been disappointing, edaravone (free radical scavenger) was approved for the treatment of acute ischemic stroke in Japan. In the future, thrombolytic and neuroprotective drugs will be used in combination.     

Preservation of global and regional left ventricular function after early thrombolysis in acute myocardial infarction

The effect of early myocardial reperfusion (within 4 hours after onset of symptoms) on regional left ventricular function in patients with acute myocardial infarction has been quantitated by analysis of segmental wall motion. Of 533 patients randomized either to conventional coronary care unit therapy or to a reperfusion strategy, in 332 high quality angiograms were obtained 2 to 8 weeks after the onset of myocardial infarction. In those assigned to thrombolytic therapy, angiographic data were also available after acute reperfusion. Analysis on an "intention to treat" basis revealed significant preservation of left ventricular function after thrombolytic therapy (ejection fraction 53%) compared with conventional treatment (ejection fraction 47%). In addition, wall motion analysis showed significant improvement of regional function in the infarct zone in both inferior and anterior infarction. In addition, significant changes occurred in regional function of the remote "noninfarct zone" in the acute as well as the chronic stage. It is concluded that improved regional and global left ventricular function can be achieved with early reperfusion and that this is the likely explanation for the reduction of early and late mortality after thrombolysis observed in this study.     

Management of Patients with Heparin-Induced Thrombocytopenia: Focus on Recombinant Hirudin

It remains controversial whether percutaneous transluminal coronary angioplasty (PTCA) performed 24 hours after the onset of acute myocardial infarction (AMI) in coronary arteries with 99% stenosis is useful in preserving left ventricular function. We investigated the effectiveness of PTCA in preventing left ventricular remodeling when it was performed 24 hours after the onset of AMI in infarct-related coronary arteries (IRCAs) having 99% stenosis and thrombolysis in myocardial infarction (TIMI) grade 3 flow. The subjects were 19 patients with AMI (anterior wall, 9 patients; inferior wall, 7 patients; and non-Q, 3 patients) who, within 24 hours of the onset of AMI, underwent coronary angiography and left ventriculography during the acute and/ or chronic phases. The patients were divided into a PTCA group, comprised of patients in whom PTCA was successfully performed 24 hours after the onset of AMI (n = 10), and a non-PTCA group (n = 9). The non-PCTA group included patients who were successfully reperfused by thrombolysis and did not include patients who had spontaneous reperfusion or reperfusion after PTCA. In the non-PTCA group, the left ventricular end-diastolic volume (mean ± SD) was significantly increased in the chronic phase (86 ± 23 mL/m² as compared with the acute phase (67 ± 13 mL/m², whereas in the PTCA group no significant difference was observed between end-diastolic volumes in the acute and chronic phases (67 ± 26 and 68 ± 13 mL/m², respectively). Left ventricular remodeling is prevented by PTCA when it is performed 24 hours after the onset of AMI in IRCAs with 99% stenosis and TIMI grade 3 flow.     

Late myocardial salvage: time to recognize its reality in the reperfusion therapy of acute myocardial infarction.

The prevailing opinion in the reperfusion therapy of patients with acute myocardial infarction (AMI) is that the benefit of reperfusion is mostly confined to the first 12 h after the symptom onset. This opinion is based on the results of the prior megatrials of thrombolytic therapy and the experimental studies. Thrombolytic studies have unequivocally proven that the efficacy of thrombolysis to salvage ischaemic myocardium is drastically reduced with the increase in the time-to-treatment interval. A relatively large number of patients present beyond the limit efficacy of thrombolysis and are considered ineligible for this reperfusion modality. Recent experimental and clinical evidence indicates that a large amount of viable myocardium is still present in the area at risk in patients with AMI presenting late after symptom onset and considered ineligible for thrombolysis. In this review, we summarized the existing data demonstrating that this viable myocardium is salvageable given the primary percutaneous coronary intervention (PCI) is used as a reperfusion therapy. By emphasizing this fact, we do not mean to contest the concept of time dependence of myocardial necrosis following coronary occlusion and time dependence of efficacy of interventions performed early (within 2-3 h) after symptom onset or to dissuade the early coronary interventions in patients with AMI. Instead, we strongly recommend the primary PCI in patients with AMI presenting late after onset of myocardial ischaemia.     

Efficacy of early reperfusion therapy at the acute stage of myocardial infarction in elderly patients: the USIK database

The role of early reperfusion therapy at the acute stage of myocardial infarctus in elderly patients is debated. The aim of this study was to analyze the prognostic role of reperfusion with i.v. thrombolysis or primary PTCA in the nationwide USIK database, which prospectively included all pts admitted to a CCU for an AMI < 48 hours in France in November 1998. For the purpose of the present study, only patients admitted within 24 hours of AMI and with one-year follow-up available were included. Of the 1838 patients included, 785 were > 70 years-old, of whom 225 (29%) had early reperfusion therapy with thrombolysis (N = 173) or primary PTCA (N = 52). Patients treated with early reperfusion had a baseline profile that differed substantially from that of patients treated conventionally: women (31% vs 50%, p < 0.001), admission within six hours of symptom onset (84% vs 55%, p < 0.001), history of systemic hypertension (48% vs 60%, p < 0.002), stroke (5% vs 11%, p < 0.01), peripheral arterial disease (8% vs 18%, p < 0.001); congestive heart failure (5% vs 20%, p < 0.001) or previous MI (12% vs 25%, p < 0.001), more anterior location of current MI (40% vs 28%, p < 0.002). Overall one-year Kaplan-Meier survival was 78% for patients with versus 64% for those without reperfusion therapy (p < 0.01). In patients with Q wave myocardial infarction, Cox multivariate analysis showed that reperfusion therapy was an independent predictor of survival (RR 0.66; 95% Confidence Interval: 0.45-0.96), along with age, anterior location and history of congestive heart failure. Therefore, data from this large "real life" registry indicate that reperfusion therapy with either thrombolysis or primary PTCA is associated with improved one-year survival in patients over 70 years of age.     

Acute Ischemic Stroke Successfully Treated Using Sequenced Intravenous and Intra-Arterial Thrombolysis and Argatroban Anticoagulation: A Case Study

BACKGROUND: Direct thrombin inhibitors, a class of anticoagulants distinct from heparins, have not been evaluated for immediate use after thrombolytic therapy in acute ischemic stroke. We report a case of ischemic stroke and prothrombotic state treated using sequenced intravenous and intra-arterial thrombolytic therapy and argatroban anticoagulation. CASE DESCRIPTION: A 19-year-old man with a complicated history of recurrent life-threatening thrombosis presented at the emergency department with acute ischemic stroke. The patient received standard-dose intravenous alteplase starting 2.25 hours after symptom onset without change in his global aphasia and right hemiparesis. Five hours after symptom onset, intra-arterial reteplase was administered for treatment of a left internal carotid "T" occlusion, with successful recanalization of the left internal carotid artery, A1 and M1 segments, and right middle cerebral anterior division and with improvement in symptoms. Argatroban therapy was started after completion of intra-arterial thrombolysis, i.e., 8.5 hours after symptom onset, and was maintained for 14 days. Although the patient sustained a small left basal ganglia infarct, he improved significantly over the course of therapy and was discharged to home without bleeding or further thrombotic episodes. CONCLUSIONS: Sequenced intravenous and intra-arterial thrombolytic therapy and argatroban anticoagulation was used successfully to safely treat a patient with ischemic stroke and comorbid prothrombotic state within 8.5 hours of symptom onset.