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| 2. |
- Berge, Eivind, et al.
(författare)
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Effects of alteplase on survival after ischaemic stroke (IST-3) : 3 year follow-up of a randomised, controlled, open-label trial
- 2016
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Ingår i: Lancet Neurology. - 1474-4422 .- 1474-4465. ; 15:10, s. 1028-34
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The effect of alteplase on patient survival after ischaemic stroke is the subject of debate. We report the effect of intravenous alteplase on long-term survival after ischaemic stroke of participants in the Third International Stroke Trial (IST-3).METHODS: In IST-3, done at 156 hospitals in 12 countries (Australia, Europe, and the UK), participants (aged >18 years) were randomly assigned with a telephone voice-activated or web-based system in a 1:1 ratio to treatment with intravenous 0·9 mg/kg alteplase plus standard care or standard care alone within 6 h of ischaemic stroke. We followed up participants in the UK and Scandinavia (Sweden and Norway) for survival up to 3 years after randomisation using data from national registries and compared survival in the two groups with proportional hazards survival analysis, adjusting for key prognostic variables. IST-3 is registered with the ISRCTN registry, number ISRCTN25765518.FINDINGS: Between May 5, 2000, and July 27, 2011, 3035 participants were enrolled in IST-3. Of these, 1948 (64%) of 3035 participants were scheduled for analysis of 3 year survival, and 1946 (>99%) of these were included in the analysis (967 [50%] in the alteplase plus standard care group and 979 [50%] in the standard care alone group). By 3 years after randomisation, 453 (47%) of 967 participants in the alteplase plus standard care group and 494 (50%) of 979 in the standard care alone group had died (risk difference 3·6% [95% CI -0·8 to 8·1]). Participants allocated to alteplase had a significantly higher hazard of death during the first 7 days (99 [10%] of 967 died in the alteplase plus standard care group vs 65 [7%] of 979 in the standard care alone group; hazard ratio 1·52 [95% CI 1·11-2·08]; p=0·004) and a significantly lower hazard of death between 8 days and 3 years (354 [41%] of 868 vs 429 [47%] of 914; 0·78 [0·68-0·90]; p=0·007).INTERPRETATION: Alteplase treatment within 6 h after ischaemic stroke was associated with a small, non-significant reduction in risk of death at 3 years, but among individuals who survived the acute phase, treatment was associated with a significant increase in long-term survival. These results are reassuring for clinicians who have expressed concerns about the effect of alteplase on survival.FUNDING: Heart and Stroke Scotland, UK Medical Research Council, Health Foundation UK, Stroke Association UK, Research Council of Norway, AFA Insurance, Swedish Heart Lung Fund, Foundation of Marianne and Marcus Wallenberg, Polish Ministry of Science and Education, Australian Heart Foundation, Australian National Health and Medical Research Council, Swiss National Research Foundation, Swiss Heart Foundation, Assessorato alla Sanita (Regione dell'Umbria), and Danube University.
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- Lewis, Steff C., et al.
(författare)
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Predicting outcome in hyper-acute stroke : validation of a prognostic model in the Third International Stroke Trial (IST3)
- 2008
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Ingår i: Journal of Neurology, Neurosurgery and Psychiatry. - London, UK : BMJ Publishing Group Ltd. - 0022-3050 .- 1468-330X. ; 79:4, s. 397-400
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND AND PURPOSE: Models are used to adjust for case mix and to stratify treatment allocation in clinical trials and can, if accurate enough, be used to aid decision-making in individual patients. We aimed to validate, in patients assessed within 6 hours of onset, a previously described six simple variable (SSV) model that was developed in stroke patients who were assessed sub-acutely. The explanatory variables in the model are age, living alone, independent pre-stroke, Glasgow Coma Scale verbal score, ability to lift arms and ability to walk.METHODS: The six variables were collected at randomisation in the Third International Stroke Trial (IST3) trial of recombinant tissue plasminogen activator in ischaemic stroke. We assessed survival to 30 days and functional status at 6 months using the Oxford Handicap Scale. We constructed receiver operator characteristic (ROC) curves to establish the model's discriminatory performance and tested its calibration by charting predicted versus actual outcomes.RESULTS: 537 patients (mean age, 74 years) were included, of whom 422 (79%) survived 30 days and 179 (33%) were alive and independent at 6 months. The SSV model had an area under the ROC curve of 0.73 for 30-day survival and 0.82 for independent survival at 6 months. Calibration was satisfactory.CONCLUSIONS: This study confirms the external validity of the SSV model in an ischaemic stroke population assessed within 6 hours of symptom onset. The SSV model comprising easily collected variables can therefore be used to stratify patients in hyper-acute stroke trials, but probably is not accurate enough for decision-making in individual patients.
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| 4. |
- Mair, Grant, et al.
(författare)
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Arterial Obstruction on Computed Tomographic or Magnetic Resonance Angiography and Response to Intravenous Thrombolytics in Ischemic Stroke
- 2017
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Ingår i: Stroke. - 0039-2499 .- 1524-4628. ; 48:2, s. 353-360
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND AND PURPOSE: Computed tomographic angiography and magnetic resonance angiography are used increasingly to assess arterial patency in patients with ischemic stroke. We determined which baseline angiography features predict response to intravenous thrombolytics in ischemic stroke using randomized controlled trial data.METHODS: We analyzed angiograms from the IST-3 (Third International Stroke Trial), an international, multicenter, prospective, randomized controlled trial of intravenous alteplase. Readers, masked to clinical, treatment, and outcome data, assessed prerandomization computed tomographic angiography and magnetic resonance angiography for presence, extent, location, and completeness of obstruction and collaterals. We compared angiography findings to 6-month functional outcome (Oxford Handicap Scale) and tested for interactions with alteplase, using ordinal regression in adjusted analyses. We also meta-analyzed all available angiography data from other randomized controlled trials of intravenous thrombolytics.RESULTS: In IST-3, 300 patients had prerandomization angiography (computed tomographic angiography=271 and magnetic resonance angiography=29). On multivariable analysis, more extensive angiographic obstruction and poor collaterals independently predicted poor outcome (P<0.01). We identified no significant interaction between angiography findings and alteplase effect on Oxford Handicap Scale (P≥0.075) in IST-3. In meta-analysis (5 trials of alteplase or desmoteplase, including IST-3, n=591), there was a significantly increased benefit of thrombolytics on outcome (odds ratio>1 indicates benefit) in patients with (odds ratio, 2.07; 95% confidence interval, 1.18-3.64; P=0.011) versus without (odds ratio, 0.88; 95% confidence interval, 0.58-1.35; P=0.566) arterial obstruction (P for interaction 0.017).CONCLUSIONS: Intravenous thrombolytics provide benefit to stroke patients with computed tomographic angiography or magnetic resonance angiography evidence of arterial obstruction, but the sample was underpowered to demonstrate significant treatment benefit or harm among patients with apparently patent arteries.CLINICAL TRIAL REGISTRATION: URL: http://www.isrctn.com. Unique identifier: ISRCTN25765518.
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- Mair, Grant, et al.
(författare)
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Effect of alteplase on the CT hyperdense artery sign and outcome after ischemic stroke.
- 2016
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Ingår i: Neurology. - 0028-3878 .- 1526-632X. ; 86:2, s. 118-25
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To investigate whether the location and extent of the CT hyperdense artery sign (HAS) at presentation affects response to IV alteplase in the randomized controlled Third International Stroke Trial (IST-3).METHODS: All prerandomization and follow-up (24-48 hours) CT brain scans in IST-3 were assessed for HAS presence, location, and extent by masked raters. We assessed whether HAS grew, persisted, shrank, or disappeared at follow-up, the association with 6-month functional outcome, and effect of alteplase. IST-3 is registered (ISRCTN25765518).RESULTS: HAS presence (vs absence) independently predicted poor 6-month outcome (increased Oxford Handicap Scale [OHS]) on adjusted ordinal regression analysis (odds ratio [OR] 0.66, p < 0.001). Outcome was worse in patients with more (vs less) extensive HAS (OR 0.61, p = 0.027) but not in proximal (vs distal) HAS (p = 0.420). Increasing age was associated with more HAS growth at follow-up (OR 1.01, p = 0.013). Treatment with alteplase increased HAS shrinkage/disappearance at follow-up (OR 0.77, p = 0.006). There was no significant difference in HAS shrinkage with alteplase in proximal (vs distal) or more (vs less) extensive HAS (p = 0.516 and p = 0.580, respectively). There was no interaction between presence vs absence of HAS and benefit of alteplase on 6-month OHS (p = 0.167).CONCLUSIONS: IV alteplase promotes measurable reduction in HAS regardless of HAS location or extent. Alteplase increased independence at 6 months in patients with and without HAS.CLASSIFICATION OF EVIDENCE: This study provides Class I evidence that for patients within 6 hours of ischemic stroke with a CT hyperdense artery sign, IV alteplase reduced intra-arterial hyperdense thrombus.
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| 6. |
- Mair, Grant, et al.
(författare)
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Effect of IV alteplase on the ischemic brain lesion at 24-48 hours after ischemic stroke.
- 2018
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Ingår i: Neurology. - 0028-3878 .- 1526-632X. ; 91:22, s. e2067-e2077
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To determine whether alteplase alters the development of ischemic lesions on brain imaging after stroke.METHODS: The Third International Stroke Trial (IST-3) was a randomized controlled trial of IV alteplase for ischemic stroke. We assessed CT or brain MRI at baseline (pretreatment) and 24 to 48 hours posttreatment for acute lesion visibility, extent, and swelling, masked to all other data. We analyzed associations between treatment allocation, change in brain tissue appearances between baseline and follow-up imaging, and 6-month functional outcome in IST-3. We performed a meta-analysis of randomized trials of alteplase vs control with pre- and postrandomization imaging.RESULTS: Of 3,035 patients recruited in IST-3, 2,916 had baseline and follow-up brain imaging. Progression in either lesion extent or swelling independently predicted poorer 6-month outcome (adjusted odds ratio [OR] = 0.92, 95% confidence interval [CI] 0.88-0.96, p < 0.001; OR = 0.73, 95% CI 0.66-0.79, p < 0.001, respectively). Patients allocated alteplase were less likely than controls to develop increased lesion visibility at follow-up (OR = 0.77, 95% CI 0.67-0.89, p < 0.001), but there was no evidence that alteplase reduced progression of lesion extent or swelling. In meta-analysis of 6 trials including IST-3 (n = 4,757), allocation to alteplase was associated with a reduction in ischemic lesion extent on follow-up imaging (OR = 0.85, 95% CI 0.76-0.95, p = 0.004).CONCLUSION: Alteplase was associated with reduced short-term progression in lesion visibility. In meta-analysis, alteplase reduced lesion extent. These findings may indicate that alteplase improves functional outcome by reducing tissue damage.CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that IV alteplase impedes the progression of ischemic brain lesions on imaging after stroke.
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