Cath Lab Digest

From *University at Buffalo, State University of New York, Buffalo, New York and §Millard Fillmore Gates Hospital, Kaleida Health; Departments of Neurosurgery & Radiology and Toshiba Stroke Research Center, Buffalo, New York.

Manuscript submitted July 29, 2009, provisional acceptance given August 17, 2009, accepted September 9, 2009.

Correspondence: L. Nelson Hopkins, MD, University at Buffalo, State University of New York, Neurosurgery, 3 Gates Circle, Buffalo, NY 14209. E-mail: lnhbuffns@aol.com

Disclosures: Dr. Hopkins receives research support from Toshiba; serves as a consultant to Abbott, Boston Scientific, Cordis, Micrus, and W. L. Gore; has a financial interest in AccessClosure, Boston Scientific, and Micrus; serves as a board member, trustee, or holds an officer position in AccessClosure and Micrus; and receives honoraria from Bard, Boston Scientific, and Cordis. Dr. Levy receives research grant support (principal investigator: Stent-Assisted Recanalization in acute Ischemic Stroke, SARIS), other research support (devices), and honoraria from Boston Scientific and research support from Micrus Endovascular and ev3; has ownership interests in Intratech Medical Ltd. and Mynx/Access Closure; serves as a consultant on the board of Scientific Advisors to Codman Neurovascular/Cordis Corporation; serves as a consultant per project and/or per hour for Micrus Endovascular, ev3, and TheraSyn Sensors, Inc.; and receives fees for carotid stent training from Abbott Vascular and ev3. Dr. Levy receives no consulting salary arrangements. All consulting is per project and/or per hour. Dr. Siddiqui has received research grants from the University at Buffalo and from the National Institutes of Health (NINDS 1R01NS064592-01A1, Hemodynamic induction of pathologic remodeling leading to intracranial aneurysms); is a consultant to Codman Neurovascular/Cordis Corporation, Concentric Medical, ev3, and Micrus Endovascular; serves on speakers’ bureaus for Codman Neurovascular/Cordis Corporation and Genentech; and has received honoraria from Genentech, Neocure Group LLC, an American Association of Neurological Surgeons’ course, and an Emergency Medicine Conference and from Codman Neurovascular/Cordis Corporation for training other neurointerventionists. Dr. Siddiqui receives no consulting salary arrangements. All consulting is per project and/or per hour. Dr. Karmon and Dr. Natarajan have no disclosure information to report.

Abstract

In this article, we provide a snapshot of the strengths and limitations of current FDA-approved stroke therapies and discuss the rationale, technique, outcomes, limitations, and future of stent-assisted recanalization.

Current FDA-approved Stroke Therapies

Acute ischemic stroke intervention has been galvanized by the correlation of clinical outcome with radiographic revascularization.^1–6 Data from several well-designed trials demonstrate that recanalization is associated with improved outcome.^1–10 A critical corollary to the importance of recanalization is the importance of time-to-recanalization.^6–8 These realizations are directing government policy, reimbursement patterns, and overall physician interest toward increased commitment to developing rapid recanalization tools and creating an infrastructure to ensure patients receive such therapies.

The recanalization rates achieved with intravenous (IV) recombinant tissue plasminogen activator (rt-PA) for proximal, large-vessel arterial occlusion are poor and range from only 10% for internal carotid artery (ICA) occlusion to 30% for middle cerebral artery (MCA) occlusion.¹¹ Intravenous thrombolysis (IVT) is not as effective for thromboembolic obstruction of these large proximal vessels as compared with more distal, smaller vessels.¹² A National Institutes of Health Stroke Scale (NIHSS) score of > 12 suggests an occlusion of a proximal large vessel and therefore, a high thrombus burden.¹³ The main concerns with intra-arterial (IA) and IV pharmacological thrombolysis have been the rate of hemorrhage, the inability to effectively dissolve platelet-rich clots, lengthy times to recanalization, and the inability to prevent abrupt reocclusion at the initial site of obstruction.14 Reocclusion has been reported to occur after IVT (in 34% of patients) and IA pharmacologic thrombolysis (in 17%) and is associated with poor outcomes.^15,16 Endovascular mechanical therapies yield higher recanalization rates and allow a slightly broader treatment window, and hence, lead to better outcomes in this group of patients. The Merci® mechanical clot retriever (Concentric Medical, Mountain View, California) and the Penumbra device (Penumbra, Inc., Alameda, California) are mechanical thrombectomy devices that have been approved by the FDA for patients with stroke symptoms in whom IV rt-PA therapy is a failure or a contraindication.^9,17 Although recanalization with the newer-generation Merci^® mechanical clot retriever, in conjunction with pharmacological therapy, is successful in 70% of patients,⁹ this rate is only marginally superior to the 66% recanalization rate in the Prolyse in Acute Cerebral Thromboembolism II trial.18 The recanalization rate with the device alone was only 50%, multiple passes (average 5–6) were required before establishment of flow in the occluded vessel and concomitant use of IA fibrinolytics increased the rate of hemorrhagic transformation. With the Penumbra device, despite an 81.6% recanalization rate, only 25% of patients recovered to a modified Rankin Scale (mRS) score of ≤ 2, with mortality at 3 months in 32.8% and symptomatic intracranial hemorrhage (ICH) in 11.2%; furthermore, it took an average of 40 minutes to achieve flow restoration after delivery of the device to the target vessel.¹⁹