Introduction

TrialAuthorsOutcome
Lancet. 2005 Feb 26-Mar 4;365(9461):764-72. Effect of timing and method of enteral tube feeding for dysphagic stroke patients (FOOD): a multicentre randomised controlled trial. Dennis MS, Lewis SC, Warlow C; FOOD Trial CollaborationEarly tube feeding might reduce case fatality, but at the expense of increasing the proportion surviving with poor outcome. Our data do not support a policy of early initiation of PEG feeding in dysphagic stroke patients.
Thrombectomy TrialsAuthorsOutcome
A trial of imaging selection and endovascular treatment for ischemic stroke. N Engl J Med. 2013;368:914-23. MR RESCUE Investigators. Kidwell CS, Jahan R, Gornbein J, et alA favorable penumbral pattern on neuroimaging did not identify patients who would differentially benefit from endovascular therapy for acute ischemic stroke, nor was embolectomy shown to be superior to standard care.
Endovascular therapy for ischemic stroke with perfusion-imaging selection (EXTEND-IA). NEJM. 2015;372:1009-18. Campbell B, Mitchell P, Kleinig T, et al.In patients with ischemic stroke with a proximal cerebral arterial occlusion and salvageable tissue on CT perfusion imaging, early thrombectomy with the Solitaire FR stent retriever, as compared with alteplase alone, improved reperfusion, early neurologic recovery, and functional outcome
Stent-Retriever Thrombectomy after Intravenous t-PA vs. t-PA Alone N Engl J Med 2015; 372:2285-2295 DOI: 10.1056/NEJMoa1415061 SWIFT PRIME Investigators* In patients receiving intravenous t-PA for acute ischemic stroke due to occlusions in the proximal anterior intracranial circulation, thrombectomy with a stent retriever within 6 hours after onset improved functional outcomes at 90 days. (Funded by Covidien; SWIFT PRIME ClinicalTrials.gov number
Endovascular therapy for acute ischaemic stroke: the Pragmatic Ischaemic Stroke Thrombectomy Evaluation (PISTE) randomised, controlled trial. J Neurol Neurosurg Psychiatry 2017;88:38-44. Muir KW, Ford GA, Messow C on behalf of the PISTE Investigators, et alThe trial did not find a significant difference between treatment groups for the primary end point. However, the effect size was consistent with published data and across primary and secondary end points. Proceeding as fast as possible to MT after CTA confirmation of large artery occlusion on a background of intravenous alteplase is safe, improves excellent clinical outcomes and, in the per-protocol population, improves disability-free survival.
Thrombectomy for Stroke at 6 to 16 Hours with Selection by Perfusion Imaging February 22, 2018 N Engl J Med 2018; 378:708-718 DOI: 10.1056/NEJMoa1713973 Gregory W. Albers, M.D.et al. for the DEFUSE 3 Investigators* Endovascular thrombectomy for ischemic stroke 6 to 16 hours after a patient was last known to be well plus standard medical therapy resulted in better functional outcomes than standard medical therapy alone among patients with proximal middle-cerebral-artery or internal-carotid-artery occlusion and a region of tissue that was ischemic but not yet infarcted
Thrombectomy 6 to 24 Hours after Stroke with a Mismatch between Deficit and Infarct. January 4, 2018 N Engl J Med 2018; 378:11-21 Raul G. Nogueira, M.D. et al. for the DAWN Trial InvestigatorsAmong patients with acute stroke who had last been known to be well 6 to 24 hours earlier and who had a mismatch between clinical deficit and infarct, outcomes for disability at 90 days were better with thrombectomy plus standard care than with standard care alone.
Thrombolysis TrialsAuthorsOutcome
Tissue plasminogen activator for acute ischemic stroke. N Engl J Med. 1995;333:1581-7. 2. The National Institute of Neurological Disorders and Stroke rt-PA Study Group.Despite an increased incidence of symptomatic intracerebral hemorrhage, treatment with intravenous t-PA within three hours of the onset of ischemic stroke improved clinical outcome at three months.
Intravenous thrombolysis with recombinant tissue plasminogen activator for acute hemispheric stroke: the European Cooperative Acute Stroke Study (ECASS). JAMA 1995;274:1017-1025Hacke W, Kaste M, Fieschi C, et al. Intravenous thrombolysis in acute ischemic stroke is effective in improving some functional measures and neurologic outcome in a defined subgroup of stroke patients with moderate to severe neurologic deficit and without extended infarct signs on the initial CT scan. However, the identification of this subgroup is difficult and depends on recognition of early major CT signs of early infarction. Therefore, since treating ineligible patients is associated with an unacceptable increase of hemorrhagic complications and death, intravenous thrombolysis cannot currently be recommended for use in an unselected population of acute ischemic stroke patients.
Thrombolysis with alteplase 3 to 4.5 hours after acute ischemic stroke. NEJM. 2008;359:1317-29.ECASS 3 Hacke W, Kaste M, Bluhmki E, et al. As compared with placebo, intravenous alteplase administered between 3 and 4.5 hours after the onset of symptoms significantly improved clinical outcomes in patients with acute ischemic stroke; alteplase was more frequently associated with symptomatic intracranial hemorrhage.
The benefits and harms of intravenous thrombolysis with recombinant tissue plasminogen activator within 6 h of acute ischaemic stroke (the third international stroke trial [IST-3]): a randomised controlled trial The Lancet , Volume 379 , Issue 9834 , 2352 - 2363 The IST-3 collaborative group For the types of patient recruited in IST-3, despite the early hazards, thrombolysis within 6 h improved functional outcome. Benefit did not seem to be diminished in elderly patients.
Randomised double-blind placebo-controlled trial of thrombolytic therapy with intravenous alteplase in acute ischaemic stroke (ECASS II). Lancet. 1998; 352: 1245-1251 Hacke, W, Kaste, M, Fieschi, C et al. The results do not confirm a statistical benefit for alteplase. However, we believe the trend towards efficacy should be interpreted in the light of evidence from previous trials. Despite the increased risk of intracranial haemorrhage, thrombolysis with alteplase at a dose of 0ยท9 mg/kg in selected patients may lead to a clinically relevant improvement in outcome.
Neurosurgical TrialsAuthorsOutcome
Surgical decompression for space-occupying cerebral infarction (the Hemicraniectomy After Middle Cerebral Artery infarction with Life-threatening Edema Trial [HAMLET]): a multicentre, open, randomised trial Lancet Neurol. 2009 Apr;8(4):326-33 HAMLET investigators Surgical decompression reduces case fatality and poor outcome in patients with space-occupying infarctions who are treated within 48 h of stroke onset. There is no evidence that this operation improves functional outcome when it is delayed for up to 96 h after stroke onset. The decision to perform the operation should depend on the emphasis patients and relatives attribute to survival and dependency.
Decompressive Surgery for the Treatment of Malignant Infarction of the Middle Cerebral Artery (DESTINY) Stroke 2007;38:2518-2525 DESTINY Study Group DESTINY showed that hemicraniectomy reduces mortality in large hemispheric stroke. With 32 patients included, the primary end point failed to demonstrate statistical superiority of hemicraniectomy, and the projected sample size was calculated to 188 patients. Despite this failure to meet the primary end point, the steering committee decided to terminate the trial in light of the results of the joint analysis of the 3 European hemicraniectomy trials.
Hemicraniectomy in Older Patients with Extensive Middle-Cerebral-Artery Stroke N Engl J Med 2014; 370:1091-1100 DESTINY II Investigators Hemicraniectomy increased survival without severe disability among patients 61 years of age or older with a malignant middle-cerebral-artery infarction. The majority of survivors required assistance with most bodily needs. DESTINY II Current Controlled Trials number,
Medical management with or without interventional therapy for unruptured brain arteriovenous malformations (ARUBA): a multicentre, non-blinded, randomised trial. Lancet 383:614-621, 2014 Mohr JP, Parides MK, Stapf C, Moquete E, Moy CS, Overbey JR, et al: The ARUBA trial showed that medical management alone is superior to medical management with interventional therapy for the prevention of death or stroke in patients with unruptured brain arteriovenous malformations followed up for 33 months. The trial is continuing its observational phase to establish whether the disparities will persist over an additional 5 years of follow-up.
Hemicraniectomy in the management of malignant middle cerebral artery infarction: Lessons from randomized, controlled trials Surg Neurol Int. 2014; 5: 72. Author Outcome
Reference Author Outcome
Reference Author Outcome
Anticoagulation for AFAuthorsOutcome
Rivaroxaban versus Warfarin in Nonvalvular Atrial Fibrillation September 8, 2011 N Engl J Med 2011; 365:883-891 The ROCKET AF Steering Committee et al. for the ROCKET AF Investigators* In patients with atrial fibrillation, rivaroxaban was noninferior to warfarin for the prevention of stroke or systemic embolism. There was no significant between-group difference in the risk of major bleeding, although intracranial and fatal bleeding occurred less frequently in the rivaroxaban group
Dabigatran versus Warfarin in Patients with Atrial Fibrillation N Engl J Med 2009; 361:1139-1151 The RE-LY Steering Committee and Investigators In patients with atrial fibrillation, dabigatran given at a dose of 110 mg was associated with rates of stroke and systemic embolism that were similar to those associated with warfarin, as well as lower rates of major hemorrhage. Dabigatran administered at a dose of 150 mg, as compared with warfarin, was associated with lower rates of stroke and systemic embolism but similar rates of major hemorrhage.
Apixaban versus Warfarin in Patients with Atrial Fibrillation N Engl J Med 2011; 365:981-992 ARISTOTLE Committees and Investigators* In patients with atrial fibrillation, apixaban was superior to warfarin in preventing stroke or systemic embolism, caused less bleeding, and resulted in lower mortality
Edoxaban versus Warfarin in Patients with Atrial Fibrillation N Engl J Med 2013; 369:2093-2104 ENGAGE AF-TIMI 48 Investigators* Both once-daily regimens of edoxaban were noninferior to warfarin with respect to the prevention of stroke or systemic embolism and were associated with significantly lower rates of bleeding and death from cardiovascular causes.
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