You are in: eMedicine Specialties > Neurology > Neuro-vascular Diseases Mechanical Thrombolysis in Acute StrokeArticle Last Updated: Nov 2, 2006AUTHOR AND EDITOR INFORMATIONSection 1 of 11
 
Author: Helmi L Lutsep, MD, Associate Professor, Department of Neurology, Oregon Health and Science University; Associate Director, Oregon Stroke Center Helmi L Lutsep is a member of the following medical societies: American Academy of Neurology and American Stroke Association Editors: Richard M Zweifler, MD, Professor, Director of Stroke Center, Director of Neurosonology Lab, Director of Vascular Neurology Fellowship, Director of Medical Student Education, Department of Neurology, University of South Alabama; Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine; Howard S Kirshner, MD, Professor of Neurology, Psychiatry and Hearing and Speech Sciences, Vice Chairman, Department of Neurology, Vanderbilt University School of Medicine; Director, Vanderbilt Stroke Center; Program Director, Stroke Service, Vanderbilt Stallworth Rehabilitation Hospital; Consulting Staff, Department of Neurology, Nashville Veterans Affairs Medical Center; Selim R Benbadis, MD, Professor, Director of Comprehensive Epilepsy Program, Departments of Neurology and Neurosurgery, University of South Florida School of Medicine, Tampa General Hospital; Nicholas Y Lorenzo, MD, Chief Editor, eMedicine Neurology; Consulting Staff, Neurology Specialists and Consultants Author and Editor Disclosure Synonyms and related keywords: mechanical thrombectomy, endovascular thrombectomy, intraarterial treatment of acute stroke, intra-arterial treatment of acute stroke, IA treatment of acute stroke, intraarterial thrombolysis, intra-arterial thrombolysis, IA thrombolysis, tissue-type plasminogen activator, tissue plasminogen activator, tPA, t-PA, mechanical thrombolysis in acute stroke INTRODUCTIONSection 2 of 11
 
At present, intravenous (IV) tissue-type plasminogen activator (tPA) is the only medical therapy approved for treatment of acute stroke in the United States. Almost 50% of patients treated with tPA in the trial by the National Institutes of Neurologic Disorders and Stroke (NINDS) achieved essentially full recovery. However, subgroup analyses of the NINDS data showed that patients with severe strokes have only an 8% likelihood of achieving clinically significant improvement with tPA. The poor outcome in these patients has inspired the search for acute-stroke treatments that are more effective than tPA. One treatment involves the use of catheters to directly deliver a clot-disrupting or retrieval device to a thromboembolus that is occluding a cerebral artery. Mechanical thrombolytic devices can remove a clot in a matter of minutes, whereas pharmaceutical thrombolytics, even those delivered intra-arterially (IA), take as long as 2 hours to dissolve a thrombus. This timesaving feature has encouraged the use of long treatment windows in trials of acute-stroke treatments. In addition, IA delivered devices were anticipated to lower rates of intracranial hemorrhage (ICH) compared with IA pharmaceutical lytics. A number of mechanical thrombolysis devices have entered clinical trials for treatment of acute stroke. These devices have used suction-creating saline jets, laser energy, ultrasound, and a corkscrew apparatus to treat strokes. Other mechanical approaches have not been assessed in clinical trials. One such method takes advantage of the suction created by pulling back on a syringe, and another uses a snare to retrieve a clot. Most devices are used in cerebral vessels that 2-5 mm, and mechanical clot thrombolysis should be performed at an institution where angiography is available because catheters are used to deliver the device to the clot during angiography. This article reviews these devices and the known clinical safety data. For excellent patient education resources, visit eMedicine's Stroke Center. Also, see eMedicine's patient education article Stroke. DISCONTINUED STUDY: ANGIOJET SYSTEMSection 3 of 11
The AngioJet system (Possis Medical, Inc, Minneapolis, MN) uses saline jets that are directed back into the catheter to create a low-pressure zone around the catheter tip, inducing suction (see Images 1-2). The clot is pulled into the exhaust lumen and removed from the vessel. Although US Food and Drug Administration (FDA) has approved this device for use in arteriovenous dialysis grafts and fistulae and for the treatment of coronary arteries, saphenous vein grafts, and peripheral vessels, clinical trials for the treatment of acute stroke are no longer in progress. The randomized Vein Graft AngioJet Study (VeGAS 2) trial was conducted to compare treatment with the AngioJet system with urokinase followed by percutaneous treatment to revascularize both native coronary arteries and saphenous vein bypass grafts in 349 patients. Patients receiving AngioJet treatment had in-hospital outcomes significantly better than those of the other patients, though 30-day event rates were similar in the 2 groups. However, the primary endpoints comprised a large number of events: stroke, death, myocardial infarction, target lesion revascularization, creatine kinase MB release, Thrombolysis in Myocardial Infarction (TIMI) blood-flow grade less than 3, and stenosis less than 50% of vascular diameter. For the treatment of thromboemboli causing stroke, a device was developed to fit the size of the internal carotid artery (ICA). Two centers reported their experiences using the AngioJet system to treat ICA occlusion. In 3 patients, the device was used to debulk extensive ICA clots to allow for access to intracranial vessels. The thrombectomy was technically feasible, and clot burden was reduced in all patients. However, despite angiographic successes, clinical outcomes were poor. The authors postulated that these outcomes likely represented poor collateral flow in these patients. Possis Medical, Inc, designed a small device to allow treatment of thromboemboli in vessels other than the ICA. Safety and efficacy trials were in progress to investigate its use in occlusions of the M1 or M2 segment of the middle cerebral artery (MCA), carotid terminus, vertebral arteries, and basilar arteries within 6 hours of symptom onset. Between April 2000 and July 2003, 22 patients were enrolled in the Thrombectomy in Middle Cerebral Artery Embolism (TIME) trial. Two, and possibly 3, vessel perforations occurred, with subarachnoid hemorrhage. The company has stopped the trials. DISCONTINUED STUDY: LATIS LASER DEVICESection 4 of 11
The Latis laser device (Latis, Inc, Coon Rapids, MN) used laser energy to ablate clots. The device was evaluated in a safety and feasibility trial at 2 centers in the United States. Arteries 2-5 mm in diameter could be treated, including the ICA, M1 or M2 branch of the MCA, A1 branch of the anterior cerebral artery (ACA), basilar artery, posterior cerebral artery (PCA), and vertebral artery. Patients could receive treatment as late as 8 hours after symptom onset in the anterior circulation and within 24 hours in the posterior circulation. A preliminary account of the first 5 patients enrolled in the trial reported that the device could not be delivered to the clot in 2. Enrollment stopped at 12 patients. Although the catheter design was changed, an efficacy trial was not pursued. DISCONTINUED STUDY: ENDOVASCULAR PHOTO ACOUSTIC RECANALIZATION LASERSection 5 of 11
The first mechanical thrombolysis device for which safety and feasibility results in patients with stroke were reported was the Endovascular Photo Acoustic Recanalization (EPAR) laser system (EndoVasix, Inc, Belmont, CA). A laser power source generated energy for the system. The energy was delivered by means of fiberoptics to the tip of the catheter at the treatment site. Absorption of laser light by darkly pigmented materials (ie, the clot) occurred inside the 1-mm catheter tip, and the system was designed to minimize scattering of laser light. Absorption converted photo energy to acoustic energy, which then emulsified the clot inside the catheter tip (see Images 3-5). Initial safety results for the EPAR system in the IA treatment of acute stroke were reported in February 2001, and final results were published in 2004. The trial was performed at 6 centers in the United States and in Germany. Patients received treatment for occlusions in the ICA, vertebral artery, basilar artery, ACA, MCA, and PCA. They were treated within 6 hours of stroke onset if they had a lesion in the anterior circulation and within 12 hours if they had a lesion in the posterior circulation. The median baseline National Institutes of Health Stroke Scale (NIHSS) score was 19 (range, 6-39). In patients in whom the device was deployed, recanalization occurred in 12 (44%) of 27 who received EPAR treatment plus adjuvant therapy but only 4 (15%) treated with the device alone. ICH occurred in 2 (7%) patients: 1 (10%) of 10 treated with the device alone and in 1 (6%) of 17 who received an adjuvant in addition to the device. About 38% of patients died. The EPAR laser system showed acceptable safety, causing no complications during active lasering. However, 1 vessel ruptured during manual injection with a 1-mL syringe (instead of the recommended 3-mL syringe), causing the distal catheter to balloon and fatal vascular rupture. Although an international efficacy trial was approved to evaluate this device in treatment of acute stroke, loss of funding stopped further clinical testing. ONGOING STUDIES: EKOS ULTRASOUND DEVICE, PENUMBRA SYSTEMSection 6 of 11
EKOS ultrasound As its name suggests, the Ultrasound Thrombolytic Infusion Catheter (EKOS Corporation, Bothell, WA) combines the use of a distal ultrasound transducer with infusion of a thrombolytic agent through the microcatheter (see Images 6-8). Ultrasound changes the structure of the clot to temporarily increase its permeability while providing an acoustic pressure gradient to move the drug into the clot to speed its dissolution. In a preclinical study investigating the efficacy of the device in peripheral vascular occlusion, thrombi were induced in the bilateral superficial femoral arteries of 9 dogs. Although urokinase 5000 IU/kg was delivered to the vessels on both sides, the ultrasound transducer of the catheter was activated on only 1 side. After treatment, angiography showed good flow (ie, TIMI grade 2 or 3) in 9 (100%) of the ultrasound-treated segments and in 6 (67%) of the controls not treated (P = .058). Angioscopy and histopathology revealed more thrombi in the vessels that did not receive treatment than in those that did. In human studies, results from the first 14 patients with acute stroke were reported in April 2000. In a safety and feasibility study, ultrasound was used with IA tPA infusion. The EKOS catheter was placed in the proximal portion of the clot. After a 2-mg bolus of tPA was injected through the catheter, the patient received a continuous infusion of IA tPA 0.3 mg/min to a maximum of 20 mg and simultaneous ultrasound transmission for as long as 60 minutes. One patient was treated with a total of 4 units of recombinant reteplase (Retavase) hand-injected over 60 minutes. Five patients with MCA thrombi and in 5 patients with carotid-T occlusions were treated within 6 hours of symptom onset, and 4 patients with posterior-circulation strokes were treated within 24 hours. The median NIHSS score was 19.5 (range, 9-27). TIMI grade 2-3 flow was attained in 8 (57%) of 14 patients in the first hour. The average time to recanalization was 46 minutes. No adverse events attributable to the catheter occurred. After briefly considering a safety and feasibility trial using IA prourokinase in conjunction with the device, the EKOS Corporation pursued another trial with tPA. In this trial, called the Interventional Management of Stroke (IMS) II trial, patients were first treated with IV tPA at a dose of 0.6 mg/kg within 3 hours. Those with persistent clots received IA tPA in conjunction with ultrasound therapy. Indirect comparisons of the IMS II trial results with those in the NINDS tPA trial that included only those patients with an NIHSS of at least 10 and age 80 years or less suggested that outcomes were at least as favorable at 3 months in the IMS II study. IMS III will compare IV tPA treatment alone to lower-dose IV tPA plus one of a few intra-arterial treatments in patients in whom treatment is initiated within 3 hours. Penumbra system The Penumbra system (Penumbra, Inc.) provides a dual approach to clot extraction, using aspiration followed by clot retrieval with a "ring" device, if needed. An initial safety trial has been completed in Europe, and a study assessing the safety and efficacy of the system for recanalization of vessels is now in progress primarily in the United States. Patients are included up to 8 hours after symptom onset. APPROVED DEVICE: MECHANICAL EMBOLUS REMOVAL IN CEREBRAL ISCHEMIA SYSTEMSection 7 of 11
The FDA has approved the Mechanical Embolus Removal in Cerebral Ischemia (MERCI) retrieval system, a corkscrew-like apparatus, "to remove blood clots from the brain in patients experiencing an ischemic stroke" (Concentric Medical, Inc, Mountain View, CA) (see Images 9-10). The corkscrew itself resides in the catheter tip, which shields it from the wall of the vessel until it is ready to be burrowed into the clot. Once lodged in the clot, the device and clot are withdrawn from the vessel. MERCI 1 study Results for the first 28 patients treated within an 8-hour window as part of this multicenter safety trial, were published in 2004. Occlusions of the ICA, proximal segments of the MCA, basilar artery, or vertebral arteries were included. Successful recanalization (TIMI grades 2 or 3) occurred in 12 patients (43%) with the retriever alone and in 18 (64%) with additional IA tPA. No symptomatic ICH occurred. MERCI study Results of the full MERCI trial, in which the device was deployed in 141 of 151 patients, were published in 2005. The mean NIHSS score was 20.1 (standard deviation [SD] ± 6.6). Recanalization with the device occurred in 68 patients (48%), which was significantly better than the rate in the placebo arm of the Prolyse in Acute Cerebral Thromboembolism (PROACT) II trial of patients with MCA occlusions (P <.0001). Additional adjuvant therapy led to recanalization in 85 (60%) subjects. Symptomatic ICH occurred in 7 (8%) of 90 patients who were treated with the device alone and in 11 (8%) of 141 who received adjuvant treatment. Mortality rates in the 141 patients in whom the device was deployed was 44% (60 of 136), and the percentage with a modified Rankin score of 2 or less at 90 days was 28% (36 of 130). Multi-MERCI study The Multi-MERCI study included patients who had persistent clots after IV tPA treatment, as well as other patients with acute stroke who presented within 8 hours of symptom onset, like those in MERCI. Twenty-seven percent of patients received IV tPA and treatment with the MERCI Retriever. Results for 111 patients showed a recanalization rate of 54% (60 of 111) with the device alone and 69% (77 of 111) with the device plus adjuvant treatment. Symptomatic ICH occurred in 10% (8 of 81) of patients treated with the device alone and in 7% (2 of 30) of those treated with device plus IV tPA. The Retriever has approval for use in patients with persistent vessel occlusion after IV tPA. NINDS has funded a randomized trial of the MERCI Retriever compared with medical therapy as long as 8 hours after symptom onset, called Magnetic Resonance and Recanalization of Stroke Clots Using Embolectomy (MR RESCUE). The effects of therapy will be stratified by the presence of a penumbra on MRI at randomization. DEVICES NOT EVALUATED IN ACUTE-STROKE TRIALSSection 8 of 11
Snarelike devices In anecdotal reports, interventionists used retrieval devices to remove thrombi from cerebral vessels. Snares, such as the Neuronet snare (Guidant Endovascular, Santa Clara, CA), have been developed specifically for use in the treatment of strokes. These devices are simple in design and do not require the clot to be amenable to emulsification. X-Sizer device Yet another approach to mechanical clot disruption involves a device with small, moving blades at the catheter tip. This device, the X-Sizer device (EndiCor Medical, San Clemente, CA), can be used to excise the thrombus and aspirate it. The device was being evaluated in randomized studies of coronary vessels and in a registry of patients with acute myocardial infarction. Although the manufacturer had modified the device for use in cerebral vessels, a safety and feasibility study was indefinitely suspended after only 1 patient was treated with the device in Europe. Suction thrombectomy This method of mechanical thrombolysis is one of the simplest. In this readily available technique, suction is applied with a syringe to remove thrombus in the ICA. It requires no other devices. The use of suction thrombectomy in 2 patients with angiographically visualized ICA thrombus with TIMI grade 0 or 1 flow was reported in 1999. Patient 1 (NIHSS score, 12) was treated 17 hours after the onset of progressive right hemispheric symptoms, and patient 2 (NIHSS score, 23) was treated 5 hours after an abrupt onset of a severe neurologic deficit. A catheter with a large inner diameter (Brite Tip; Cordis Corporation, Miami, FL) was placed in the symptomatic vessel and navigated over a guidewire into the thrombus. A 60-mL syringe was used to aspirate the thrombus. Each patient required angioplasty and stenting of carotid bifurcation stenosis and received daily aspirin and ticlopidine after the procedure. No complications occurred. Both patients had excellent angiographic results, which showed minimal residual ICA stenosis and improved distal flow. Patient 1 had full functional recovery and a 3-month NIHSS score of 2, but patient 2 had a 3-month NIHSS score of 22. CONCLUSIONS AND FUTURE CONSIDERATIONSSection 9 of 11
Clinical trials have shown that thrombectomy with mechanical thrombolysis devices is indeed feasible in the treatment of acute stroke. Although a number of such devices have been discontinued, some because of financial considerations, one, the Concentric MERCI Retriever, has received FDA clearance. The EKOS ultrasound device and the Penumbra System continue to be evaluated in trials and other approaches are being considered. Because few patients with stroke arrive at the hospital quickly enough to receive IV tPA, mechanical thrombolysis potentially extends the treatment window because they act promptly at the site of the thrombus. The devices can retrieve large clots that pharmaceutical agents may not successfully lyse. Patients treated with IV tPA may be considered for treatment of residual clot with some of these devices. The MERCI Retriever has shown success in recanalizing vessels, though its overall effect on clinical outcomes of the patients with severe stroke in its studies is somewhat unclear. Although researchers had also hoped that the MERCI Retriever and other IA delivered devices would lower ICH rates compared with pharmaceutical thrombolytics delivered in the same manner, study results to date have not borne this out. ICH rates have been similar to the 10% reported from a randomized trial in which patients with MCA strokes received IA prourokinase within 6 hours of symptom onset. However, hemorrhages occurring with the use of mechanical devices have included subarachnoid and intraparenchymal hemorrhages. Because relatively few patients with stroke and angiographically visualized clots present soon after symptom onset, trials have been designed to enhance the likelihood of their completion. Study designs have included the primary use of angiographic outcomes and clots in more than 1 vascular distribution, as well as the use of historical controls. The high morbidity rate of this patient population and the cost of the procedure have led to the use of historical controls instead of a traditional control group, especially one randomized to receive placebo. However, this approach to facilitate the approval of devices compared with medical therapies has been controversial. Comparisons with medical treatments must still be done to assess clinical outcomes and the financial impact of these devices. The MR RESCUE trial is the first study to begin addressing this need. In the end, clots may best be treated with a combined approach by using various devices, lytics, and antithrombotics. In the future, referring patients with acute stroke to designated stroke centers that are equipped to offer these treatments must be considered. MULTIMEDIASection 10 of 11
REFERENCESSection 11 of 11
Mechanical Thrombolysis in Acute Stroke excerpt Article Last Updated: Nov 2, 2006 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
