International journal of stroke : official journal of the International Stroke Society
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Randomized Controlled Trial
Rationale, design, and baseline participant characteristics in the MRI and cognitive substudy of the cardiovascular outcomes for people using anticoagulation strategies trial.
Covert vascular disease of the brain manifests as infarcts, white matter hyperintensities, and microbleeds on MRI. Their cumulative effect is often a decline in cognition, motor impairment, and psychiatric disorders. Preventive therapies for covert brain ischemia have not been established but represent a huge unmet clinical need. ⋯ The COMPASS MRI substudy will examine the effect of the antithrombotic interventions on MRI-determined covert brain infarcts and cognition. Demonstration of a therapeutic effect of the antithrombotic regimens on brain infarcts would have implications for prevention of cognitive decline and provide insight into the pathogenesis of vascular cognitive decline.
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Stroke symptoms can be unsettling, even when symptoms resolve, but focusing on stroke prevention can be empowering provided that effective interventions for appropriate patient populations are available. Current options include interventions for symptomatic carotid artery stenosis, anticoagulation for atrial fibrillation, high-dose statins, new oral anticoagulants, new developments in atrial fibrillation detection, and new therapeutics are in development. For antiplatelet therapy, aspirin monotherapy is effective but dual antiplatelet therapy with the combination of aspirin and clopidogrel increases hemorrhage risks over the long term that outweigh potential benefits. ⋯ Furthermore, since clopidogrel is a prodrug that must be metabolized to have antiplatelet activity, it is not surprising that the treatment effect in CHANCE was limited to patients who were not carriers of loss-of-function alleles for clopidogrel metabolism. Ticagrelor, an antiplatelet agent which failed to meet its primary endpoint as monotherapy compared to aspirin in the Acute Stroke or Transient Ischaemic Attack Treated with Aspirin or Ticagrelor and Patient Outcomes (SOCRATES) trial, is currently being tested as combination therapy with aspirin compared to aspirin alone in Acute Stroke or Transient Ischaemic Attack Treated With Ticagrelor and ASA for Prevention of Stroke and Death (THALES). These developments along with improvements to the infrastructure to perform rapid evaluations and to apply intensive secondary stroke prevention interventions hold continued promise for the future.
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Treatment of individuals with asymptomatic carotid artery stenosis is still handled controversially. Recommendations for treatment of asymptomatic carotid stenosis with carotid endarterectomy (CEA) are based on trials having recruited patients more than 15 years ago. Registry data indicate that advances in best medical treatment (BMT) may lead to a markedly decreasing risk of stroke in asymptomatic carotid stenosis. The aim of the SPACE-2 trial (ISRCTN78592017) was to compare the stroke preventive effects of BMT alone with that of BMT in combination with CEA or carotid artery stenting (CAS), respectively, in patients with asymptomatic carotid artery stenosis of ≥70% European Carotid Surgery Trial (ECST) criteria. ⋯ The low sample size of this prematurely stopped trial of 513 patients implies that its power is not sufficient to show that CEA or CAS is superior to a modern medical therapy (BMT) in the primary prevention of ischemic stroke in patients with an asymptomatic carotid stenosis up to one year after treatment. Also, no evidence for differences in safety between CAS and CEA during the first year after treatment could be derived. Follow-up will be performed up to five years. Data may be used for pooled analysis with ongoing trials.
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Alteplase has been the mainstay of thrombolytic treatment since the National Institutes of Neurological Disorders and Stroke trial was published in 1995. Over recent years, several trials have investigated alternative thrombolytic agents. ⋯ We review the literature on tenecteplase for the treatment of acute ischemic stroke, with a focus on the major completed and ongoing trials. Overall, tenecteplase shows promise for treatment of acute ischemic stroke, both in populations currently eligible for alteplase and also in groups not currently treated with thrombolysis.