Opinion statement
Since the advent of intravenous thrombolytic therapy with recombinant tissue plasminogen activator (tPA) for acute ischemic stroke, there has been a marked change in our management approach to patients with acute ischemie stroke. Although the major part of our focus in treating patients with stroke remains prevention of complications post-stroke and reduction of stroke recurrence, there is a paradigm shift to immediate “clot” lysis. This concept is being actively promoted through certification of institutions as stroke centers in order to increase the number of patients with stroke treated in an ultra-rapid fashion. However, options for acute treatment remain limited. Other than aspirin, the only US Food and Drug Administration-approved agent for acute ischemie stroke is intravenous tPA. Some physicians treating patients with acute ischemic stroke still frequently use heparin and low-molecular-weight heparinoids, but there are no firm data to support routine use of this drug class. However, a number of new lytic agents and strategies are being pursued. Some of these treatments, such as intra-arterial chemical thrombolysis or mechanical intra-arterial thrombolysis, are available only at specialized stroke centers. In addition, new antithrombotic agents are being studied. Drugs that can rescue neurons from impending hypoxiaischemia cell death represent the “holy grail” of acute stroke therapy. To date, these “neuroprotectant” strategies have been unsuccessful, although this concept remains under active investigation in animal and human trials.
Similar content being viewed by others
References and Recommended Reading
Heart Disease and Stroke Statistics-2005 Update. Dallas, IX: American Heart Association; 2005. An excellent resource for stroke epidemiology data.
National Institute of Neurological Disorders and Stroke rt-PA Stroke Study Group: Tissue plasminogen activator for acute ischemic stroke. N Engl J Med 1995,333:1581–1587. The foundation for modern acute stroke therapy (see Ingall et al. [4] and Hacke et al. [5] for elaboration).
Lenzer J, Warlow C, Saver JL, et al.: Alteplase for stroke: money and optimistic claims buttress the “brain attack” campaign (commentary); Thrombolysis in stroke: it works (commentary). BMJ 2002, 324:723–729. A fascinating debate, although somewhat of a polemic on the part of the critics of tPA.
Ingall TJ, O’Fallon WM, Asplund K, et al.: Findings from the reanalysis of the NINDS Tissue Plasminogen Activator for Acute Ischemie Stroke Trial. Stroke 2004, 35:2418–2424. Important for awareness of the current issues related to study that provides the foundation for modern acute stroke therapy[2] and the study by Lenzer et al. [3].
Hacke W, Donnan G, Fieschi C, et al.: Association of outcome with early stroke treatment: pooled analysis of ATLANTIS, ECASS and NINDS rt-PA stroke trials. Lancet 2004, 363:768–774. Highlights the importance of early stroke treatment.
Wardlaw JM, del Zoppo G, Yamaguchi T, et al.: Thrombolysis for ischemie stroke. Cochrane Database Syst Rev 2000, 2:CD00213; Update in Cochrane Database Syst Rev 2003, 3:CD000213.
Beneficial effect of carotid endarterectomy in symptomatic patients with high-grade carotid stenosis. North American Symptomatic Carotid Endarterectomy Trial Collaborators. N Engl J Med 1991, 325:445-453.
Fagan S, Morgenstern L, Petitta A, et al.: Cost-effectiveness of tissue plasminogen activator for acute ischemie stroke. Neurology 1998, 50:883–890.
Katzan IL, Furlan AJ, Lloyd LE: Use of tissue-type plasminogen activator for acute ischemie stroke: the Cleveland area experience. JAMA 2000, 283:1151–1158.
Katzan IL, Hammer MD, Furlan AJ, et al.: Quality improvement and tissue-type plasminogen activator for acute ischemie stroke. Stroke 2003, 34:799–800. Evidence of the success of quality improvement programs for stroke.
Alberts MJ, Hademenos G, Latchaw RE, et al.: Recommendations for the establishment of primary stroke centers. JAMA 2000, 283:3102–3109. Highlights the creation of organized stroke systems.
Alberts MJ, Latchaw RE, Selman WR, et al.: Recommendations for comprehensive stroke centers. A consensus statement from the Brain Attack Coalition. Stroke 2005, 36:1597–1616. Highlights the creation of organized stroke systems.
Ramsey D, Smithard DG, Kalra L: Early assessments of dysphagia and aspiration risk in acute stroke patients. Stroke 2003, 34:1252–1257.
Hilker R, Poetter C, Findeisein N, et al.: Nosocomial pneumonia after acute stroke. Implications for neurological intensive care medicine. Stroke 2003, 34:975–981.
Petty GW, Brown RD Jr, Whisnant JP, et al.: Frequency of major complications of aspirin, warfarin, and intravenous heparin for secondary stroke prevention: a population-based study. Ann Intern Med 1999, 130:14–22.
The International Stroke Trial (IS): a randomized trial of aspirin, subcutaneous heparin, both, or neither among 19435 patients with acute ischaemic stroke. International Stroke Trial Collaborative Group. Lancet 1997, 349:1569-1581.
CAST: randomized placebo-controlled trial of early aspirin use in 20,000 patients with acute ischaemic stroke. CAST (Chinese Acute Stroke Trial) Collaborative Group. Lancet 1997, 349:1641-1649.
Chen ZM, Sandercock P, Han HC, et al.: Indications for early aspirin use in acute ischemic stroke: a combined analysis of 40,000 randomized patients from the Chinese Acute Stroke Trial and the International Stroke Trial. On behalf of the CAST and IST collaborative groups. Stroke 2000, 31:1240–1249.
Hochman JS, Wali AU, Gavrila D, et al.: A new regimen for heparin use in acute coronary syndromes. Am Heart J 1999, 138:313–318.
Caplan LR: Resolved: heparin may be useful in selected patients with brain ischemia. Stroke 2003, 34:230–231. Emphasizes the lack of data regarding a therapy still widely used but with limited clinical evidence.
Sandercock P: Full heparin anticoagulation should not be used in acute ischemic stroke. Stroke 2003, 34:231–232. Emphasizes the lack of data regarding a therapy still widely used but with limited clinical evidence.
Donnan GA, Davis SM: Heparin in stroke: not for most, but the controversy lingers. Stroke 2003, 34:232–233. Emphasizes the lack of data regarding a therapy still widely used but with limited clinical evidence.
Chamorro A, Busse O, Obach V, et al.: The Rapid Anticoagulation Prevents Ischemie Damage (RAPID) study in acute stroke. Cerebrovasc Dis 2005, 19:402–404.
Hankey GJ, Counsell C, Sandercock P: Low molecular weight heparins or heparinoids versus standard unfractionated heparin for acute ischemie stroke. The Cochrane Library 2002, 2.
Low molecular weight heparinoid, ORG 10172 (danaparoid) and outcome after ischemic stroke. A randomized controlled trial. TOAST Investigators. J Am Med Assoc 1998, 279:1265-1272.
Adams HP Jr, Bendixine BH, Leira E, et al.: Antithrombotic treatment of ischemie stroke among patients with occlusion or severe stenosis of the internal carotid artery: a report of the Trial of Org 10172 in Acute Stroke Treatment (TOAST). Neurology 1999, 53:122–125.
Sarma GR, Roy AK: Nadroparin plus aspirin versus aspirin alone in the treatment of acute ischemic stroke. Neurol India 2003, 51:208–210.
Kay R, Wong KS, Yu YL, et al.: Low molecular weight heparin for the treatment of acute ischemie stroke. N Engl J Med 1995, 333:1588–1593.
AdamsHP Jr, Adams RJ, Brott T, et al.: Guidelines for the early management of patients with ischemic stroke: a scientific statement from the Stroke Council of the American Stroke Association. Stroke 2003, 34:1056–1083. Important summary statement about acute stroke therapy.
Intracerebral hemorrhage after intravenous tPA therapy for ischemic stroke. The NINDS TPA Stroke Study Group. Stroke 1997, 28:2109-2118.
Haley EC Jr, Lyden PD, Johnston KC, et al.: A pilot dose-escalation safety study of tenecteplase in acute ischemic stroke. Stroke 2005, 36:607–612.
Hacke W, Albers G, Al-Rawi Y, et al.: The Desmoteplase in Acute Ischemie Stroke Trial (DIAS): a phase II MRI-based 9 hour window acute stroke thrombolysis trial with intravenous desmoteplase. Stroke 2005, 36:66–73. Important study that is one of the first stroke studies to determine enrollment based on imaging criteria.
Emergency administration of abciximab for treatment of patients with acute ischemie stroke. Results of a randomized phase 2 trial. Abciximab Emergent Stroke Treatment Trial (AbESTT) Investigators. Stroke 2005, 36:880-890. A therapy representing an alternative intravenous strategy to tPA.
LaMonte MP, Nash ML, Wang DZ, et al.: Argatroban anticoagulation in patients with acute ischemie stroke (ARGIS-1): a randomized placebo-controlled safety study. Stroke 2004, 35:1677–1682.
Fisher M, Ratan R: New perspectives on developing acute stroke therapy. Ann Neurol 2003, 53:10–20.
Magnesium for acute stroke. Intravenous Magnesium Efficacy in Stroke (IMAGES) Study Investigators. Lancet 2004, 363:439-445.
Saver JL, Kidwell C, Eckstein M, et al.: Prehospital neuroprotective therapy for acute stroke: results of the Field Administration of Stroke Therapy-Magnesium (FAST-MAG) pilot trial. Stroke 2004, 35:106–108. Another alternative intravenous strategy to tPA, highlighting the importance of ultra-rapid treatment.
FurlanA, Higashida R, Wechsler L, et al.: Intra-arterial prourokinase for acute ischemie stroke. The PROACT II Study: a randomized clinical trial. JAMA 1999, 282:2003–2011. The landmark study of intra-arterial therapy.
Chalela JA, Katzan I, Liebeskind DS, et al.: Safety of intra-arterial thrombolysis in the post-operative period. Stroke 2001, 32:1365–1369.
Ramee SR, Subramanian R, Felberg RA, et al.: Catheter-based treatment for patients with acute ischemic stroke ineligible for intravenous thrombolysis. Stroke 2004, 35:109–111.
Combined intravenous and intra-arterial recanalization for acute ischemic stroke: the Interventional Management of Stroke (IMS) Study. IMS Study Investigators. Stroke 2004, 35:904-911.
Qureshi AI, Ali Z, Suri MF, et al.: Intra-arterial third generation recombinant tissue plasminogen activator (reteplase) for acute ischemie stroke. Neurosurgery 2001, 49:41–48.
Arnold M, Nedeltchev K, Schroth G, et al.: Clinical and radiological predictors of recanalization and outcome of 40 patients with acute basilar artery occlusion treated with intra-arterial thrombolysis. / Neurol Neurosurg Psychiatr 2004, 75:857–862. Evidence that the time-window for thrombolytic therapy is not uniform.
Phan TG, Wijdicks EF: Intra-arterial thrombolysis for vertebrobasilar circulation ischemia. Crit Care Clin 1999, 15:719–742.
Gobin YP, Starkman S, Duckwiler S, et al.: MERCI 1: a phase one study of mechanical embolus removal in cerebral ischemia. Stroke 2004, 35:2848–2853.
Smith WS, Sung G, Starkman S, et al.: Safety and efficacy of mechanical embolectomy in acute ischemie stroke. Results of the MERCI trial. Stroke 2005, 36:1432–1438. An interesting single-arm study.
Alexandrov AV, Molina CA, Grotta JC, et al.: Ultra-sound-enhanced systemic thrombolysis for acute ischemie stroke. N Engl J Med 2004, 351:2170–2178. An interesting application of noninvasive and portable technology in conjunction with standard drug therapies.
Polak JF: Ultrasound energy and the dissolution of thrombus. N Engl J Med 2004, 351:2154–2155.
Kammersgaard LP, Jorgensen HS, Rungby RA, et al.: Admission body temperature predicts long-term mortality after acute stroke: the Copenhagen Stroke Study. Stroke 2002, 33:1759–1762.
Hajat C, Hajat S, Sharma P: Effects of post-stroke pyrexia on stroke outcome: a meta-analysis of studies in patients. Stroke 2000, 31:410–414. A rationale for the treatment of hypothermia in stroke patients.
Krieger DW, Yenari MA: Therapeutic hypothermia for acute ischemic stroke. What do laboratory studies teach us? Stroke 2004, 35:1482–1489.
Wang H, Olivero W, Lanzino G, et al.: Rapid and selective cerebral hypothermia achieved using a cooling helmet. Neurosurg 2004, 100:272–277.
Adams RJ: Lessons from the Stroke Prevention Trial in Sickle Cell Anemia (STOP). Child Neurol2000, 15:344–349.
Gabis LV, Yangala R, Lenn NJ: Time lag to diagnosis of stroke in children. Pediatrics 2002, 110:924–928.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Schneck, M.J., Biller, J. New treatments in acute ischemic stroke. Curr Treat Options Neurol 7, 499–511 (2005). https://doi.org/10.1007/s11940-005-0050-y
Issue Date:
DOI: https://doi.org/10.1007/s11940-005-0050-y