Inpharma 1279 - 17 Mar 2001

An update on thrombolytic therapy Canadian experienceInterim results from an ongoing Canadian study alsofor acute stroke

indicate that clinical trial results seen in stroke patientsThrombolytic therapy for acute stroke has yet to receiving alteplase can be carried over into the

achieve the far-reaching impact that has occurred in the community hospital setting.2

treatment of myocardial infarction. A small minority of The Canadian Activase for Stroke Effectiveness Studypatients with stroke receive thrombolytic therapy, and (CASES) involves hospitals throughout Canada,delays in presentation and treatment account for much including 56 centres that have provided data on a regularof the low rate of use. However, recent studies basis, said Dr Michael Hill, a neurologist at thepresented at the 26th International Stroke Conference University of Calgary, Alberta, Canada. The study[Fort Lauderdale, US; February 2001] show that the follows a protocol similar to that used in the NINDS trial,favourable experience seen with alteplase [t-PA] in large including a 3-hour time window for treatment. Mostclinical trials can be replicated in clinical practice, patients have been treated during the final 30 minutes ofincluding the community hospital setting. Other recent the time window. About 15% of patients have beenfindings include evidence that thrombolytics can be treated beyond 3 hours.administered ‘safely’ to very elderly patients and during Preliminary outcome data on 840 patients treatedtelemedicine consultation and that pretreatment MRI* during the first 2 years suggest that about 30% ofevaluation of patients can be performed without an patients have little or no neurological deficit at 90 daysexcessive delay in treatment. and almost half can live independently. The median

A centre that participated in the National Institute of NIHSS score at presentation was 14. SymptomaticNeurological Disorders and Stroke (NINDS) t-PA Stroke haemorrhage has occurred in 4.9% of patients and theStudy has essentially replicated the efficacy results incidence has remained stable throughout the study.achieved in that trial during a 4-year clinical experience.1 ‘We are confident that this [alteplase] is as safe as inThe NINDS t-PA Stroke Study was a 2-part randomised, the clinical trials’, Dr Hill stated. ‘The risk of intracranialdouble-blind, multicentre trial that compared IV hemorrhage has not been a deterrent to treatment’, healteplase 0.9 mg/kg with placebo in 624 patients treated added.within 3 hours of the onset of acute stroke symptoms.** Dr Hill went on to say that ‘subgroups are beginning to

emerge. Good outcomes are predicted by less severeStick to the guidelinesstrokes. Older age, severe stroke and hyperglycemia allA cohort of 269 patients treated between 1996 and present an increased risk of not making a good recovery’.2000 at the University of Texas, Houston, US, had a

median National Institutes of Health Stroke Scale Effective in the elderly(NIHSS) score of 14 at enrolment and a median Another Canadian study provided reassurance thatdischarge score of 3. The patients represented 16–17% alteplase can be administered safely and with little or noof all stroke patients who were screened for treatment at loss of thrombolytic efficacy in patients aged ≥ 80 years.3

the centre, said Professor James Grotta from the Investigators compared outcomes in patients withUniversity of Texas. The number of treated patients did stroke aged 37–79 years (n = 46) with outcomes in 16not increase dramatically over the 4 years; 73 patients patients aged 80–93 years. The older patients had morewere treated in 1996–1997, 65 in 1998 and 131 in disabling strokes as reflected by the mean pretreatment1999–2000. The median time from presentation to modified Rankin Scale score of 1.5, compared with 0.6treatment was 68 minutes and ranged between 10 and for the younger patients (p = 0.01), reported Dr Bart129 minutes. Demaerschalk from London Health Sciences Centre,

Half of the 269 treated patients achieved at least a Ontario, Canada. The mean initial NIHSS score did not4-point reduction (i.e. improvement) in scores on the differ (14 for younger patients and 17 for older patients),NIHSS, compared with 47% in the NINDS trial, said nor did the time from stroke onset to treatment (151 andProfessor Grotta. 155 minutes, respectively).

‘Our data should be construed as representative of an Analysis of outcome data showed no significantexperienced center, as opposed to a community hospital between-group differences in the proportion of patientssetting’, he said. ‘All of our patients have been treated who had at least a 4-point improvement in the NIHSSwithin 3 hours of the onset of stroke’. score at 24 hours, who had an NIHSS score of 0–1 at 90

Furthermore, the incidence of symptomatic days or a modified Rankin Scale score of 0 or 1 at 90haemorrhage decreased as the number of treated days. An 81-year-old patient had a fatal intracranialpatients increased. The overall rate was 4.5%, which was haemorrhage, which was the only symptomaticsimilar to the 5% incidence reported in the NINDS trial. intracranial haemorrhage to occur.However, the rate declined to 2.2% during 1999–2000, Treatment via telemedicinecompared with 6.8% in 1996. Professor Grotta noted

Thrombolytic therapy also can be administered safelythat the incidence of haemorrhage was 13% in patientsand effectively via telemedicine consultation, accordingwho were not treated according to the NINDS protocol.to a small clinical study reported by US investigators.4

Most protocol violations involved elevated BP.In this study, 30 patients underwent telemedicine‘Up to 20% of all patients presenting with ischemic

evaluation from 2 different remote locations, and 5 ofstroke can be treated safely and successfully withthe 30 subsequently received alteplase, reported Drintravenous t-PA by an experienced stroke team’,Marian LaMonte from the University of Maryland SchoolProfessor Grotta concluded. However, he added ‘thereof Medicine, Baltimore, US.is room for improvement. A substantial percentage of

Four of the 5 treated patients had excellent recoveries,patients can be treated within an organized program. Thedefined as an NIHSS score of ≤ 1. The fifth patientrate of symptomatic hemorrhage can be kept low by aninitially had a good recovery but then had clinicalexperienced stroke care team that sticks to establishedsymptoms of reocclusion.guidelines’.

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Inpharma 17 Mar 2001 No. 12791173-8324/10/1279-0001/$14.95 Adis © 2010 Springer International Publishing AG. All rights reserved

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Emergency physicians at remote hospitals linked tothe University of Maryland are enthusiastic abouttelemedicine consultation for patients with acute stroke,said Dr LaMonte. The programme has had a modestimpact on extension of alteplase therapy – theproportion of patients with stroke receivingthrombolytic therapy at the remote locations hasincreased from 0 to 6%.

No delays with MRI?Finally, investigators from the US NIH presented data

showing that MRI evaluation of patients with strokeneed not lead to unnecessary delays in treatment.5

This conclusion came from a review of findings fromstroke patients who presented at Suburban Hospital,Bethesda, Maryland, US, which offers 24-hour access toboth MRI and computed tomography (CT) scanning. Thehospital mandates both CT and MRI scanning prior totreatment, reported Dr Steven Warach from the NINDSt-PA Stroke Study Group.

Of 12 patients evaluated for thrombolytic therapy, 8received alteplase and 4 were excluded on the basis ofMRI results. Two of the 4 excluded patients hadsubacute lesions, 1 had evidence of chronichaemorrhage and 1 had a normal MRI and a subsequentdiagnosis of Guillain-Barre syndrome, said Dr Warach.

The median time from presentation to treatment was83 minutes in the 8 patients screened by MRI andtreated. The median time from stroke onset to treatmentwas 134 minutes. Four of the 8 alteplase recipientsachieved a modified Rankin Score of 0 or 1 at follow-up.

Dr Warach and colleagues concluded that routineMRI screening of patients with acute stroke does notlead to the excessive treatment delays that have beenassociated with increases in risk for poor outcomes.* magnetic resonance imaging** see Inpharma 1018: 12, 23 Dec 1995; see Inpharma 1018 p12;800314860 and Inpharma 1024, 9–10, 17 Feb 1996; see Inpharma1024 p9-10; 800314928

1. Grotta JC, et al. Intravenous TPA for ischemic stroke patients: Houstonexperience 1996-2000. Stroke 32: 323, Jan 2001.

2. Hill MD, et al. The Canadian Activase for Stroke Effectiveness Study (CASES):interim results. Stroke 32: 323, Jan 2001.

3. Demaerschalk B, et al. Intravenous tissue plasminogen activator for acuteischemic stroke in patients greater than or equal to 80 years old: the London,Canada experience. Stroke 32: 368-369, Jan 2001.

4. LaMonte MP, et al. Safe rt-PA administration for ischemic stroke duringtelemedicine consultation. Stroke 32: 374, Jan 2001.

5. Warach S, et al. Routine screening for IV tPA therapy less than 3 hours withMRI: initial clinical experience. Stroke 32: 371, Jan 2001.

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