This Article Full Text Full Text (PDF) All Versions of this Article: 38/10/2627    most recent STROKEAHA.107.490417v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Saver, J. L. Search for Related Content PubMed PubMed Citation Articles by Saver, J. L. Pubmed/NCBI databases Medline Plus Health Information Stroke Related Collections Acute Cerebral Infarction Acute Stroke Syndromes Emergency treatment of Stroke Angiography Thrombolysis Related Article

(Stroke. 2007;38:2627.)
© 2007 American Heart Association, Inc.

Editorials

Intra-Arterial Fibrinolysis for Acute Ischemic Stroke

The Message of Melt

Jeffrey L. Saver, MD

From the Stroke Center and Department of Neurology, David Geffen School of Medicine at the University of California, Los Angeles.

Correspondence to Jeffrey L. Saver, MD, UCLA Stroke Center, 710 Westwood Plaza, Los Angeles, CA 90095. E-mail jsaver@ucla.edu

Key Words: clinical trials • endovascular • fibrinolysis • thrombolysis • urokinase

An extract of the first 250 words of the full text is provided, because this article has no abstract.

See related article, pages 2633–2639.

For nearly a decade, intra-arterial fibrinolytic therapy for acute ischemic stroke has stood poised on the threshold of a definitive evidential basis and widespread acceptance. The positive result of the phase 3 PROACT II trial in 1999 appeared to validate the pathophysiologically eminently reasonable strategy of endovascular recanalization in acute ischemic stroke.¹ Endovascular therapy delivers lytic agent at high concentration directly to the clot, increasing lysis rates compared with intravenous therapy, while minimizing systemic exposure and extracerebral bleeding complications.² Leading stroke centers adopted endovascular recanalization therapies as a common off-label treatment option for patients beyond the 3-hour window.³

However, proponents of evidence-based medicine noted that a single, small phase 3 clinical trial was insufficient to provide definitive proof of efficacy. The US Food and Drug Administration and international regulatory agencies did not approve a stroke label for pro-urokinase. The expense of a confirmatory phase 3 trial of pro-urokinase proved daunting to pharma and none was undertaken. In US national practice guidelines, intra-arterial fibrinolysis occupied a gray zone, receiving a Level B recommendation, indicating the incomplete foundation of a single dose-ranging and single positive phase 3 trial.⁴ The limitations of this evidential base have prevented regional emergency medical systems from organizing delivery of patients directly to endovascular hospitals.

The results of the MELT trial, reported in this issue of Stroke, are therefore very welcome, providing additional information regarding intra-arterial fibrinolytic therapy that complements and supports previous studies. Taking advantage of the delay until October . . . [Full Text of this Article]

Related Article:

Randomized Trial of Intraarterial Infusion of Urokinase Within 6 Hours of Middle Cerebral Artery Stroke: The Middle Cerebral Artery Embolism Local Fibrinolytic Intervention Trial (MELT) Japan

Akira Ogawa, Etsuro Mori, Kazuo Minematsu, Waro Taki, Akira Takahashi, Shigeru Nemoto, Susumu Miyamoto, Makoto Sasaki, Takashi Inoue for The MELT Japan Study Group
Stroke 2007 38: 2633-2639. [Abstract] [Full Text] [PDF]

This article has been cited by other articles:

				R. E. Latchaw, M. J. Alberts, M. H. Lev, J. J. Connors, R. E. Harbaugh, R. T. Higashida, R. Hobson, C. S. Kidwell, W. J. Koroshetz, V. Mathews, et al. Recommendations for Imaging of Acute Ischemic Stroke: A Scientific Statement From the American Heart Association Stroke, November 1, 2009; 40(11): 3646 - 3678. [Full Text] [PDF]

				R Novakovic, G Toth, and P D Purdy Review of current and emerging therapies in acute ischemic stroke JNIS, July 1, 2009; 1(1): 13 - 26. [Abstract] [Full Text] [PDF]

				J. L. Saver, G. W. Albers, B. Dunn, K. C. Johnston, M. Fisher, and for the STAIR VI Consortium Stroke Therapy Academic Industry Roundtable (STAIR) Recommendations for Extended Window Acute Stroke Therapy Trials Stroke, July 1, 2009; 40(7): 2594 - 2600. [Abstract] [Full Text] [PDF]

				R.G. Nogueira, A.J. Yoo, F.S. Buonanno, and J.A. Hirsch Endovascular Approaches to Acute Stroke, Part 2: A Comprehensive Review of Studies and Trials AJNR Am. J. Neuroradiol., May 1, 2009; 30(5): 859 - 875. [Abstract] [Full Text] [PDF]

				M. Arnold, M. Steinlin, A. Baumann, K. Nedeltchev, L. Remonda, S. J. Moser, M.-L. Mono, G. Schroth, H. P. Mattle, and R. W. Baumgartner Thrombolysis in Childhood Stroke: Report of 2 Cases and Review of the Literature Stroke, March 1, 2009; 40(3): 801 - 807. [Abstract] [Full Text] [PDF]

				A. Bose, H. Henkes, K. Alfke, W. Reith, T.E. Mayer, A. Berlis, V. Branca, S. P. Sit, and for the Penumbra Phase 1 Stroke Trial Investigator The Penumbra System: A Mechanical Device for the Treatment of Acute Stroke due to Thromboembolism AJNR Am. J. Neuroradiol., August 1, 2008; 29(7): 1409 - 1413. [Abstract] [Full Text] [PDF]