Thrombolysis for Acute Stroke in Routine Clinical Practice

Bravata, Dawn M.; Kim, Nancy; Concato, John; Krumholz, Harlan M.; Brass, Lawrence M.

doi:10.1001/archinte.162.17.1994

Cited by 105 publications

(66 citation statements)

References 28 publications

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“…23 It is also clear that if patients are not carefully selected, meeting strict inclusion and exclusion criteria, the rate of complications is increased. 24 Thus, as summarized in a practice statement of the American College of Emergency Physicians, ''There is insufficient evidence at this time to endorse the use of intravenous tPA in clinical practice when systems are not in place to ensure that the inclusion/exclusion criteria established by the NINDS guidelines for tPA use in acute stroke are followed.'' 21 When counseling patients and their families about the benefits and risks of IV tPA, one should keep in mind that the NINDS trial demonstrated increased odds of excellent outcomes despite a significant 10-fold increase in the risk of symptomatic intracranial hemorrhage (6.4% vs. 0.6%), and did not alter 30-day mortality.…”

Section: No Blood On the Ct Scan Results Back In <3 Hours From Symptmentioning

confidence: 99%

Management of ischemic stroke: Part 1. Emergency room management

Lu-Emerson

Likosky

Amin

et al. 2010

Journal of Hospital Medicine

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BACKGROUND:Acute ischemic stroke is commonly encountered by the hospitalist. There have been dramatic changes in our ability to care for these patients acutely. The Joint Commission on Accreditation of Healthcare Organizations (JCAHO) primary stroke center certification has become progressively more important to institutions nationally and includes many aspects of initial evaluation and treatment.PURPOSE:Acute treatment involves the rapid assimilation of patient characteristics, laboratory results, and imaging results. There are a growing number of potential acute therapies with a range of risk, benefit, necessary time windows, and specific eligibility criteria.DATA SOURCES:Primary trials, current guidelines.CONCLUSIONS:The hospitalist is well‐positioned to play a major role in the treatment of stroke patients as well as the systems work that aids in the management of this population. Journal of Hospital Medicine 2010;5:33–40. © 2010 Society of Hospital Medicine.

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Section: No Blood On the Ct Scan Results Back In <3 Hours From Symptmentioning

confidence: 99%

Management of ischemic stroke: Part 1. Emergency room management

Lu-Emerson

Likosky

Amin

et al. 2010

Journal of Hospital Medicine

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“…29) However, the use of rt-PA is restricted to administration within 3 h after onset of symptoms due to the risk of cerebral hemorrhage. 30) Therefore, there are strong clinical demands for neuroprotective agents that can block neuronal death associated with stroke. 31) We have developed DY-9760e, a calmodulin antagonist, which exerts neuroprotective action against cell death induced by Ca 2ϩ overload 15,17) and ameliorates brain injury that occurs after cerebral ischemia in rodents.…”

Section: Discussionmentioning

confidence: 99%

DY-9760e, a Calmodulin Antagonist, Reduces Brain Damage after Permanent Focal Cerebral Ischemia in Cats

Sugimura

Takamori

Fukushi

et al. 2005

Biological & Pharmaceutical Bulletin

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Although the cellular pathophysiological mechanisms underlying ischemic brain damage remain to be fully clarified, accumulating evidence suggests that an excessive elevation of intracellular Ca 2ϩ in neurons is a primary mechanism by which cells become injured following cerebral ischemia. 1-3)An overload of Ca 2ϩ in neurons disrupts the ionic balance and activates various Ca 2ϩ -dependent enzymes. Treatment of ischemic animals with compounds that block Ca 2ϩ entry through Ca 2ϩ -permeable channels has been shown to provide protection against the consequences of ischemia in laboratory animals, 4-6) but these treatments have not been found suitable for use in humans. 7-9)Calmodulin is a major Ca 2ϩ -binding protein found mainly in the central nervous system. 10,11) Since many of the pathways through which Ca 2ϩ acts involve Ca 2ϩ /calmodulin signaling systems, including calmodulin-dependent enzymes, inhibition of calmodulin may be a possible alternative approach towards the treatment and prevention of post-ischemic injury. In fact, it has been reported that Ca 2ϩ -bound calmodulin, which is an active form, is increased following ischemia and regional changes correlate with regions of ischemic neuronal damage.12) Furthermore, calmodulin antagonists protect cultured neurons from cell death induced by glutamate, an excitatory amino acid, and protect hippocampal CA1 neurons against hypoxia/hypoglycemia in organotypic cultures. 13,14) DY-9760e (3-[2-[4-(3-chloro-2-methylphenyl)-1-piperazinyl]ethyl]-5,6-dimethoxy-1-(4-imidazolylmethyl)-1H-indazole dihydrochloride 3.5 hydrate) is a calmodulin antagonist that is 2 to 70 times more potent than W-7, a well-known calmodulin antagonist, and can protect neurons against neuronal cell death elicited by Ca 2ϩ overload. [15][16][17] This compound ameliorates brain injury that occurs after transient or permanent focal ischemia and microembolization in rats. [18][19][20][21][22] Although these studies in various rodent models show a hopeful characteristic of DY-9760e, it is subsequently important to assess if it exerts a protective effect in a large animal model of focal cerebral ischemia. Cats, a gyrencephalic species in common with humans, have long been used both in pathophysiological studies for cerebral ischemia and in investigations for the protective efficacy of agents. [23][24][25][26][27] Therefore, the present study was designed to evaluate the potential acute therapeutic effect of DY-9760e on ischemic injury resulting from permanent middle cerebral artery (MCA) occlusion in cats. MATERIALS AND METHODSAnimals Twenty-three male Ico: Fec Eur (Tif) cats (IFFA-CREDO, L'arbresle, France), weighing 2.7 to 3.3 kg, were used in this study. The animals were maintained on canned food (CK, Oriental Yeast, Tokyo, Japan), solid food (NK-C, Nihon Nosan, Yokohama, Japan) and tap water, which were given once a day under a constant 12-h dark-light cycle. All experimental procedures were performed in accordance with the in-house guidelines of the Institutional Animal Care and Use Committee ...

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“…Moreover, the risk of major protocol violations in the administration of alteplase should be noted. In two comprehensive independent communitybased studies, the Cleveland 9 and Connecticut 10 studies (of which only the former was cited in the manufacturer's submission), such violations, most of which appeared to have been accidental, 10 affected 67% of patients receiving alteplase in Connecticut and 50% in the Cleveland area.…”

Section: Summary Of Submitted Clinical Evidencementioning

confidence: 99%

Alteplase for the treatment of acute ischaemic stroke: a single technology appraisal

Jones

Holmes

2009

Health Technol Assess

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This paper presents a summary of the evidence review group report into the clinical effectiveness and cost-effectiveness of alteplase for the treatment of acute ischaemic stroke, in accordance with the licensed indication, based upon the evidence submission from the manufacturer to the National Institute for Health and Clinical Excellence (NICE) as part of the single technology appraisal (STA) process. The submitted clinical evidence included several randomised controlled trials indicating that, in highly selected patients, alteplase administered at a licensed dose within 3 hours of the onset of acute ischaemic stroke is associated with a statistically significant reduction in the risk of death or dependency at 3 months compared with placebo, despite a significantly increased risk of symptomatic intracranial haemorrhage within the first 7-10 days. Data from the National Institute of Neurological Disorders and Stroke (NINDS) trial suggest that the benefit of treatment is sustained at 6 and 12 months. However, data from observational studies suggest that few patients with acute ischaemic stroke will be eligible for alteplase therapy under the terms of the current licensing agreement. In particular, many patients will be excluded by virtue of their age, and many more by the restriction of therapy to patients in whom treatment can be initiated within 3 hours of symptom onset. The manufacturer's submission included a state transition model evaluating the impact of treatment with alteplase within 3 hours of onset of stroke symptoms compared to standard treatment reporting that, in the base-case analysis, alteplase was both less costly and more effective than standard treatment. This increased to a maximum of approximately £4000 upon oneway sensitivity analysis of the parameters. The Discussion of ERG reports is invited. Visit the HTA website correspondence forum (www.hta.ac.uk/ correspond). DOI: 10.3310/hta13suppl2/03Alteplase for the treatment of acute ischaemic stroke: a single technology appraisal 16 probabilistic sensitivity analysis presented within the submission suggests that the probability that alteplase has a cost-effectiveness ratio greater than £20,000 per quality-adjusted life-year (QALY) gained is close to 1 (0.99). The results of the short-term model demonstrate that alteplase is cost-effective over a 12-month period, with an incremental cost-effectiveness ratio of £14,026 per QALY gained. This increased to a maximum of £50,000 upon one-way sensitivity analysis of the parameters. At 12 months, the probabilistic sensitivity analysis presented within the submission suggests that the probability that alteplase has a cost-effectiveness ratio greater than £20,000 per QALY gained is approximately 0.7. The guidance issued by NICE in April 2007 as a result of the STA states that alteplase is recommended for the treatment of acute ischaemic stroke only when used by physicians trained and experienced in the management of acute stroke and in centres with the required facilities.

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Thrombolysis for Acute Stroke in Routine Clinical Practice

Cited by 105 publications

References 28 publications

Management of ischemic stroke: Part 1. Emergency room management

Management of ischemic stroke: Part 1. Emergency room management

DY-9760e, a Calmodulin Antagonist, Reduces Brain Damage after Permanent Focal Cerebral Ischemia in Cats

Alteplase for the treatment of acute ischaemic stroke: a single technology appraisal

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