Landmark Trials in Stroke
Acute Stroke
Tissue plasminogen activator for acute ischemic stroke. The National Institute of Neurological Disorders and Stroke rt-PA Stroke Study Group.(NINDS)
New England Journal of Medicine. 1995;333(24):1581-1587.
Intra-arterial Prourokinase for Acute Ischemic Stroke. The PROACT II Study: A Randomized Controlled Trial.
Journal of the American Medical Association.1999;282:2003-2011.
Magnetic resonance imaging profiles predict clinical response to early reperfusion: the diffusion and perfusion imaging evaluation for understanding stroke evolution (DEFUSE) study.
Annals of Neurology. 2006;60(5):508-17.
MERCI 1. A Phase 1 Study of Mechanical Embolus Removal in Cerebral Ischemia. (MERCI)
Stroke. 2004;35(12):2848-54.
Carotid Endartectomy
Endarterectomy for asymptomatic carotid artery stenosis. Executive Committee for the Asymptomatic Carotid Atherosclerosis Study. (ACAS)
Journal of the American Medical Association. 1995;273(18):1421-1428.
Prevention of disabling and fatal strokes by successful carotid endarterectomy in patients without recent neurological symptoms: randomised controlled trial. (ACST)
Lancet. 2004;363:1491-1502.
Beneficial effect of carotid endarterectomy in symptomatic patients with high-grade carotid stenosis. North American Symptomatic Carotid Endarterectomy Trial Collaborators. (NASCET)
New England Journal of Medicine. 1991;325(7):445-453.
Randomised trial of endarterectomy for recently symptomatic carotid stenosis: final results of the MRC European Carotid Surgery Trial. (ECST)
Lancet. 1998;351(9113):1379-87.
Carotid Stenting
Endarterectomy versus stenting in patients with symptomatic severe carotid stenosis. (EVA-3S)
New England Journal of Medicine.2006;355(16):1660-71.
30 day results from the SPACE trial of stent-protected angioplasty versus carotid endarterectomy in symptomatic patients: a randomised non-inferiority trial.
Lancet. 2006;368(9543):1239-47.
Protected carotid-artery stenting versus endarterectomy in high-risk patients. Stenting and Angioplasty with Protection in Patients and High Risk for Endarterectomy Trial. (SAPPHIRE)
New England Journal of Medicine. 2004;351(15):1565-7.
Antiplatelet Therapy
A randomised, blinded, trial of clopidogrel versus aspirin in patients at risk of ischaemic events (CAPRIE). CAPRIE Steering Committee.
Lancet. 1996;348(9038):1329-1339.
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.
Lancet. 2004;364(9431):331-7.
European Stroke Prevention Study 2 (ESPS-2). Dipyridamole and acetylsalicylic acid in the secondary prevention of stroke.
Journal of the Neurological Sciences. 1996;143(1-2):1-13.
Aspirin plus dipyridamole versus aspirin alone after cerebral ischaemia of arterial origin (ESPRIT): randomised controlled trial.
Lancet. 2006;367(9523):1665-73.
Clopidogrel and Aspirin versus Aspirin Alone for the Prevention of Atherothrombotic Events. (CHARISMA)
New England Journal of Medicine. 2006;354(16):1706-17.
The United Kingdom transient ischaemic attack (UK-TIA) aspirin trial: final results.
Journal Neurology, Neurosurgury, and Psychiatry. 1991;54(12):1044-54.
Statin Therapy
Effects of intense low-density lipoprotein cholesterol reduction in patients with stroke or transient ischemic attack: the Stroke Prevention by Aggressive Reduction in Cholesterol Levels (SPARCL) trial.
Stroke. 2007;38(12):3198-204.
MRC/BHF Heart Protection Study of cholesterol lowering with simvastatin in 20,536 high-risk individuals: a randomised placebo-controlled trial.
Lancet. 2002;360(9326):7-22.
Blood Pressure Control
The ACCESS Study: evaluation of Acute Candesartan Cilexetil Therapy in Stroke Survivors.
Stroke. 2003;34:1699-1703.
Randomised trial of a perindopril-based blood-pressure-lowering regimen among 6,105 individuals with previous stroke or transient ischaemic attack. (PROGRESS)
Lancet. 2001;358(9287):1033-41.
Cardiovascular morbidity and mortality in the Losartan Intervention For Endpoint reduction in hypertension study (LIFE): a randomised trial against atenolol.
Lancet. 2002;359(9311):995-1003.
Morbidity and Mortality After Stroke, Eprosartan Compared with Nitrendipine for Secondary Prevention: principal results of a prospective randomized controlled study (MOSES).
Stroke. 2005;36(6):1218-26.
A comparison of outcomes with angiotensin-converting--enzyme inhibitors and diuretics for hypertension in the elderly. (ANBP)
New England Journal of Medicine. 2003;348(7):583-92.
Hemicraniectomy
Early decompressive surgery in malignant infarction of the middle cerebral artery: a pooled analysis of three randomised controlled trials
Lancet Neurology. 2007;6(3):215-22.
Sickle Cell Disease
Prevention of a first stroke by transfusions in children with sickle cell anemia and abnormal results on transcranial Doppler ultrasonography. (STOP 1)
New England Journal of Medicine. 1998;339(1):5-11
Discontinuing prophylactic transfusions used to prevent stroke in sickle cell disease. (STOP 2)
New England Journal of Medicine. 2005;353:2769-78.
Atrial Fibrillation
Stroke Prevention in Atrial Fibrillation Study. (SPAF I) Final results.
Circulation.1991;84:527-539.
Warfarin versus aspirin for prevention of thromboembolism in atrial fibrillation: Stroke Prevention in Atrial Fibrillation II Study. (SPAF II).
Lancet.1994;343:687-91.
Adjusted-dose warfarin versus low-intensity, fixed-dose warfarin plus aspirin for high-risk patients with atrial fibrillation: Stroke Prevention in Atrial Fibrillation III randomised clinical trial. (SPAF III)
Lancet. 1996;348(9028):633-638.
Secondary prevention in non-rheumatic atrial fibrillation after transient ischaemic attack or minor stroke. EAFT (European Atrial Fibrillation Trial) Study Group.
Lancet. 1993;342(8882):1255-62.
Warfarin versus aspirin for stroke prevention in an elderly community population with atrial fibrillation (the Birmingham Atrial Fibrillation Treatment of the Aged Study, BAFTA): a randomised controlled trial.
Lancet. 2007;370:493-503.
Intracranial Disease
Comparison of Warfarin and Aspirin for Symptomatic Intracranial Arterial Stenosis. (WASID)
New England Journal of Medicine. 2005;352(13):1305-16.
Anticoagulation
A comparison of warfarin and aspirin for the prevention of recurrent ischemic stroke. Warfarin-Aspirin Recurrent Stroke Study Group. (WARSS)
New England Journal of Medicine. 2001;345(20):1444-51.
A randomized trial of anticoagulants versus aspirin after cerebral ischemia of presumed arterial origin. The Stroke Prevention in Reversible Ischemia Trial (SPIRIT) Study Group.
Annals of Neurology. 1997;42(6):857-865
Intracerebral Hemorrhage
Early surgery versus initial conservative treatment in patients with spontaneous supratentorial intracerebral haematomas in the International Surgical Trial in Intracerebral Haemorrhage (STICH): a randomised trial.
Lancet. 2005;365(9457):387-397.
Recombinant Activated Factor VII Intracerebral Hemorrhage Trial Investigators. Recombinant activated factor VII for acute intracerebral hemorrhage.
New England Journal of Medicine. 2005;352(8):777-85.
Transient Ischemic Attack
Transient ischemic attack--proposal for a new definition.
New Engand Journal of Medicine. 2002;347(21):1713-6.
Short-term prognosis after emergency department diagnosis of TIA.
Journal of the American Medical Association. 2000;284(22):2901-6.
Validation and refinement of scores to predict very early stroke risk after transient ischaemic attack.
Lancet. 2007;369:283-92.
An expanded list of completed and ongoing trials in stroke is available through the Stroke Trials Registry website.
Many thanks to Drs. David Hess, Jeffrey Switzer, and Fenwick Nichols for their assistance in compiling this list of landmark clinical trials. The full text access is password protected in order to protect the integrity of the original authors work and is intended for the academic use of members of the Department of Neurology at the Medical College of Georgia.