Ancrod in Acute Ischemic Stroke

Levy, David E.; Zoppo, Gregory J. del; Demaerschalk, Bart M.; Demchuk, Andrew M.; Diener, Hans‐Christoph; Howard, George; Kaste, Markku; Pancioli, Arthur; Ringelstein, E. B.; Spatareanu, Carmen; Wasiewski, Warren W.

doi:10.1161/strokeaha.109.565119

Cited by 90 publications

(34 citation statements)

References 17 publications

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“…A follow-up clinical trial, in which 500 subjects with AIS were randomized within 6 hours of symptoms to ancrod at 0.167 IU/kg IV per hour vs placebo for 2 to 3 hours, showed no difference in clinical outcome between the 2 groups. 49 A favorable functional outcome at 39.6% in the treatment arm vs 37.2% ( p ϭ 0.47) was found.…”

mentioning

confidence: 84%

Advances in thrombolytics for treatment of acute ischemic stroke

Kirmani¹,

Alkawi²,

Panezai³

et al. 2012

Neurology

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Over the past 50 years, thrombolytic agents have been devised with the aim of recanalizing occluded coronary vessels, and later on, applied in the setting of acute ischemic stroke. Pharmacologic agents have generally targeted the plasminogen-plasmin transformation, facilitating the natural process of fibrinolysis. Newer agents with varying degrees of fibrin selectivity and pharmacologic half-life have influenced both recanalization rates and hemorrhagic complications, inside and outside the CNS. Intra-arterial (IA) administration of fibrinolytic agents increases delivery of the drug to the thrombus at a higher concentration with smaller quantities and therefore lowers systemic exposure. Mechanical thrombus disruption or extraction allows for drug delivery to a greater surface area of the thrombus. Delays associated with IA therapy may worsen the risk/ benefit ratio of thrombolysis; therefore, combinations of IA-IV treatments have been studied. To date, there are no direct comparative trials to show that endovascular administration is more efficacious or carries a lower risk of hemorrhagic complications than IV tissue plasminogen activator. Neurology ® 2012;79 (Suppl 1):S119-S125

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mentioning

confidence: 84%

Advances in thrombolytics for treatment of acute ischemic stroke

Kirmani¹,

Alkawi²,

Panezai³

et al. 2012

Neurology

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“…They are characterized by longer half life and higher fibrin specificity and, hence, a possibly lower risk of bleeding. However, recent clinical trials were disappointing (38). Therefore, in order to find effective treatment options in stroke, we need to identify novel mechanism-based targets.…”

mentioning

confidence: 99%

Neuroprotection After Stroke by Targeting NOX4 As a Source of Oxidative Stress

Radermacher

Wingler

Langhauser

et al. 2013

Antioxidants & Redox Signaling

127

107

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Significance: Stroke, a leading cause of death and disability, poses a substantial burden for patients, relatives, and our healthcare systems. Only one drug is approved for treating stroke, and more than 30 contraindications exclude its use in 90% of all patients. Thus, new treatments are urgently needed. In this review, we discuss oxidative stress as a pathomechanism of poststroke neurodegeneration and the inhibition of its source, type 4 nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (NOX4), as a conceptual breakthrough in stroke therapy. Recent Advances: Among potential sources of reactive oxygen species (ROS), the NOXes stand out as the only enzyme family that is solely dedicated to forming ROS. In rodents, three cerebrovascular NOXes exist: the superoxide-forming NOX1 and 2 and the hydrogen peroxide-forming NOX4. Studies using NOX1 knockout mice gave conflicting results, which overall do not point to a role for this isoform. Several reports find NOX2 to be relevant in stroke, albeit to variable and moderate degrees. In our hands, NOX4 is, by far, the major source of oxidative stress and neurodegeneration on ischemic stroke. Critical Issues: We critically discuss the tools that have been used to validate the roles of NOX in stroke. We also highlight the relevance of different animal models and the need for advanced quality control in preclinical stroke research. Future Directions: The development of isoform-specific NOX inhibitors presents a precious tool for further clarifying the role and drugability of NOX homologues. This could pave the avenue for the first clinically effective neuroprotectant applied poststroke, and even beyond this, stroke could provide a proof of principle for antioxidative stress therapy.

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“…The tPA duteplase [54] is used primarily in Japan; the use of streptokinase is generally avoided after evidence of an unfavourable benefit/ safety balance [55][56][57]. Recent trials of desmoteplase [58] and ancrod [59] have not indicated a benefit.…”

Section: Reperfusion To Treat Ischaemic Strokementioning

confidence: 99%

Treatment of acute stroke: an update

Mikulík

Wahlgren

2015

J Intern Med

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Stroke is the second leading cause of global mortality after coronary heart disease, and a major cause of neurological disability. About 17 million strokes occur worldwide each year. Patients with stroke often require long-term rehabilitation following the acute phase, with ongoing support from the community and nursing home care. Thus, stroke is a devastating disease and a major economic burden on society. In this overview, we discuss current strategies for specific treatment of stroke in the acute phase, focusing on intravenous thrombolysis and mechanical thrombectomy. We will consider two important issues related to intravenous thrombolysis treatments: (i) how to shorten the delay between stroke onset and treatment and (ii) how to reduce the risk of symptomatic intracerebral haemorrhage. Intravenous thrombolysis has been approved treatment for acute ischaemic stroke in most countries for more than 10 years, with rapid development towards new treatment strategies during that time. Mechanical thrombectomy using a new generation of endovascular tools, stent retrievers, is found to improve functional outcome in combination with pharmacological thrombolysis when indicated. There is an urgent need to increase public awareness of how to recognize a stroke and seek immediate attention from the healthcare system, as well as shorten delays in prehospital and within-hospital settings.

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Ancrod in Acute Ischemic Stroke

Cited by 90 publications

References 17 publications

Advances in thrombolytics for treatment of acute ischemic stroke

Advances in thrombolytics for treatment of acute ischemic stroke

Neuroprotection After Stroke by Targeting NOX4 As a Source of Oxidative Stress

Treatment of acute stroke: an update

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