Emerging therapies for cerebrovascular disorders.

New information about therapeutic interventions regarding several important aspects of cerebrovascular disease has appeared recently. This short review will focus on new therapeutic developments concerning the prevention of ischemic stroke, acute ischemic stroke therapy trials, and, lastly, the management of patients with intracranial aneurysms. Great strides have been made in the pharmacological management of patients to reduce the risk for developing ischemic stroke. Stroke prevention is now clearly a multimodal endeavor that encompasses not only the use of antithrombotic agents but also the identification and treatment of multiple, potential stroke risk factors.1 While the precise relationship of elevated total and LDL cholesterol to stroke risk remains to be determined, prior studies clearly demonstrated substantial primary stroke risk reduction with the use of various statins in patients with cardiovascular disease.2 A recent report by the Heart Protection Study Collaborative Group (HPS) suggests that the benefits of at least 1 statin, simvastatin, extend to stroke patients as well.3 In this study, 20 536 patients with 1 form of vascular disease or diabetes mellitus were randomized to 40 mg of simvastatin daily or placebo in addition to their baseline medications and followed on average for 5 years. Of patients randomized, 1820 had stroke alone and 1460 had stroke and coronary artery disease. Allocation to simvastatin was associated with an overall 25% reduction in first stroke. Patients with stroke in the study had a similar benefit for subsequent major vascular events, although precise characterization of risk reduction for secondary stroke was not provided. The results may in fact underestimate the benefits of simvastatin because on average 17% of placebo allocated patients took a nonstudy statin. The result of this study led to a change in the indications for simvastatin by the FDA, and the medication is now indicated in stroke patients, …

[1]  D. Sackett,et al.  Benefit of carotid endarterectomy in patients with symptomatic moderate or severe stenosis. North American Symptomatic Carotid Endarterectomy Trial Collaborators. , 1998, The New England journal of medicine.

[2]  AndrewJ. S. Coats.  MRC/BHF Heart Protection Study of cholesterol lowering with simvastatin in 20 536 high-risk individuals: a randomised placebocontrolled trial , 2002, The Lancet.

[3]  J. Bosch,et al.  Use of ramipril in preventing stroke: double blind randomised trial , 2002, BMJ : British Medical Journal.

[4]  P. Rothwell,et al.  Carotid endarterectomy for asymptomatic carotid stenosis: asymptomatic carotid surgery trial. , 2004, Stroke.

[5]  T. Bajwa,et al.  Protected carotid-artery stenting versus endarterectomy in high-risk patients. , 2004, The New England journal of medicine.

[6]  R. Higashida,et al.  Intra-arterial Prourokinase for Acute Ischemic Stroke: The PROACT II Study: A Randomized Controlled Trial , 1999 .

[7]  A. Demchuk,et al.  HMG-CoA reductase inhibitors (statins) , 2000, Neurology.

[8]  P. Gorelick.  Stroke Prevention Therapy Beyond Antithrombotics: Unifying Mechanisms in Ischemic Stroke Pathogenesis and Implications for Therapy: An Invited Review , 2002, Stroke.

[9]  J. Chalmers.  Perindopril Protection Against Recurrent Stroke Study (PROGRESS) , 2001 .

[10]  Mario Zuccarello,et al.  Guidelines for the Management of Spontaneous Intracerebral Hemorrhage: A Guideline for Healthcare Professionals From the American Heart Association/American Stroke Association , 2015, Stroke.

[11]  B. Davis,et al.  Major outcomes in high-risk hypertensive patients randomized to angiotensin-converting enzyme inhibitor or calcium channel blocker vs diuretic: The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT). , 2002, JAMA.

[12]  J. Farmer.  Anglo-Scandinavian cardiac outcomes trial--lipid lowering arm. , 2004, Current Atherosclerosis Reports.

[13]  S. Warach,et al.  The Desmoteplase in Acute Ischemic Stroke Trial (DIAS): A Phase II MRI-Based 9-Hour Window Acute Stroke Thrombolysis Trial With Intravenous Desmoteplase , 2005, Stroke.

[14]  D. Sackett,et al.  Beneficial effect of carotid endarterectomy in symptomatic patients with high-grade carotid stenosis. , 1991, The New England journal of medicine.

[15]  A. Mendelow,et al.  International Variations in Surgical Practice for Spontaneous Intracerebral Hemorrhage , 2003, Stroke.

[16]  R. Collins,et al.  Prevention of coronary and stroke events with atorvastatin in hypertensive patients who have average or lower-than-average cholesterol concentrations, in the Anglo-Scandinavian Cardiac Outcomes Trial—Lipid Lowering Arm (ASCOT-LLA): a multicentre randomised controlled trial , 2003, The Lancet.

[17]  H. Diener,et al.  Aspirin and clopidogrel compared with clopidogrel alone after recent ischaemic stroke or transient ischaemic attack in high-risk patients (MATCH): randomised, double-blind, placebo-controlled trial , 2004, The Lancet.

[18]  D. Nichols,et al.  Unruptured intracranial aneurysms: natural history, clinical outcome, and risks of surgical and endovascular treatment , 2003, The Lancet.

[19]  S. Yusuf.  MRC/BHF Heart Protection Study of cholesterol lowering with simvastatin in 20536 high-risk individuals: a randomised placebo-controlled trial. Commentary , 2002 .

[20]  S. Mayer.  Ultra-Early Hemostatic Therapy for Intracerebral Hemorrhage , 2003, Stroke.

[21]  H. Diener,et al.  Aspirin and clopidogrel compared with clopidogrel alone after recent ischemic stroke or transient ischemic attack in high-risk patients (MATCH): Randomized, double-blind, placebo-controlled trial , 2004 .

[22]  R. Peto,et al.  Prevention of disabling and fatal strokes by successful carotid endarterectomy in patients without recent neurological symptoms: randomised controlled trial , 2004, The Lancet.

[23]  A. Davies,et al.  Endarterectomy for asymptomatic carotid artery stenosis , 1995, BMJ.