Tissue Plasminogen Activator for Acute Ischemic Stroke National Institute of Neurological Disorders...
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Transcript of Tissue Plasminogen Activator for Acute Ischemic Stroke National Institute of Neurological Disorders...
![Page 1: Tissue Plasminogen Activator for Acute Ischemic Stroke National Institute of Neurological Disorders and Stroke rt-PA Stroke Study Group.](https://reader030.fdocuments.us/reader030/viewer/2022032607/56649ed15503460f94be01ba/html5/thumbnails/1.jpg)
Tissue Plasminogen Activator for Acute Ischemic Stroke
National Institute of Neurological Disorders and Stroke rt-PA Stroke
Study Group
![Page 2: Tissue Plasminogen Activator for Acute Ischemic Stroke National Institute of Neurological Disorders and Stroke rt-PA Stroke Study Group.](https://reader030.fdocuments.us/reader030/viewer/2022032607/56649ed15503460f94be01ba/html5/thumbnails/2.jpg)
Summarise the paper in 200 words
![Page 3: Tissue Plasminogen Activator for Acute Ischemic Stroke National Institute of Neurological Disorders and Stroke rt-PA Stroke Study Group.](https://reader030.fdocuments.us/reader030/viewer/2022032607/56649ed15503460f94be01ba/html5/thumbnails/3.jpg)
Summarise the paper in 200 words
• Aims– Compare intravenous tissue plasminogen activator (t-PA)
with placebo in treatment of acute ischaemic stroke.
• Method– 2 part double blinded multi-centre randomised controlled
trial– Patients with ischaemic stroke (no intracranial
haemorrhage on CT) within 3 hours of onset were included– Stratified block randomisation to treatment with placebo
or t-PA
![Page 4: Tissue Plasminogen Activator for Acute Ischemic Stroke National Institute of Neurological Disorders and Stroke rt-PA Stroke Study Group.](https://reader030.fdocuments.us/reader030/viewer/2022032607/56649ed15503460f94be01ba/html5/thumbnails/4.jpg)
Summarise the paper in 200 words
• Outcome measures:– Part 1: Complete resolution of neurological deficit or
improvement in NIHSS score >4 within 24 hours of onset of stroke
– Part 2: Recovery with minimal or no deficit 3 months after treatment, measured using a combination of 4 outcome measures (Barthel index, modified Rankin scale, Glasgow outcome scale, NIHSS)
![Page 5: Tissue Plasminogen Activator for Acute Ischemic Stroke National Institute of Neurological Disorders and Stroke rt-PA Stroke Study Group.](https://reader030.fdocuments.us/reader030/viewer/2022032607/56649ed15503460f94be01ba/html5/thumbnails/5.jpg)
Summarise the paper in 200 words
• Results– Part 1 (n=291): no significant difference in percentage of
patients with neurological improvement at 24 hours (relative risk =1.2 (95% CI 0.9-1.6))
– Part 2 (n=333): Odds ratio for favourable outcome in combined test statistic at 3 months in t-PA group =1.7 (95% CI 1.2-2.6, p=0.008)
– No significant difference in mortality, but higher rate of symptomatic intracerebral haemorrhage within 36hrs seen in t-PA group (p<0.001)
![Page 6: Tissue Plasminogen Activator for Acute Ischemic Stroke National Institute of Neurological Disorders and Stroke rt-PA Stroke Study Group.](https://reader030.fdocuments.us/reader030/viewer/2022032607/56649ed15503460f94be01ba/html5/thumbnails/6.jpg)
Summarise the paper in 200 words
• Conclusion– Despite an increased incidence of symptomatic
intracerebral hemorrhage, treatment with t-PA within 3 hours onset of ischemic stroke improved clinical outcome at 3 months.
![Page 7: Tissue Plasminogen Activator for Acute Ischemic Stroke National Institute of Neurological Disorders and Stroke rt-PA Stroke Study Group.](https://reader030.fdocuments.us/reader030/viewer/2022032607/56649ed15503460f94be01ba/html5/thumbnails/7.jpg)
Abstract
![Page 8: Tissue Plasminogen Activator for Acute Ischemic Stroke National Institute of Neurological Disorders and Stroke rt-PA Stroke Study Group.](https://reader030.fdocuments.us/reader030/viewer/2022032607/56649ed15503460f94be01ba/html5/thumbnails/8.jpg)
The Good...
• Multi-centre RCT• Clear power calculation performed• Few patients lost to follow up• Intention to treat analysis
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The Bad...
• Patient selection – were all eligible patients randomised?• No CONSORT diagram• Differences between placebo and treatment groups
– No mean given for NIHSS score - makes comparison difficult– Higher rate of “Large-vessel occlusive stroke” in placebo group– Higher rate of edema and mass effect in placebo group
• Unconventional statistical tests applied– (Mantel-Haenszel test and Wald test)
• No p-value given for differences in adverse events – (symptomatic intracerebral haemorrhage and serious systemic
bleeding)
![Page 10: Tissue Plasminogen Activator for Acute Ischemic Stroke National Institute of Neurological Disorders and Stroke rt-PA Stroke Study Group.](https://reader030.fdocuments.us/reader030/viewer/2022032607/56649ed15503460f94be01ba/html5/thumbnails/10.jpg)
The Bad...
• Dichotomous end-point in part 2– No assessment of magnitude of effect of treatment can be made
• Randomisation method– Permuted block design with blocks of various sizes. Stratified by
clinical centre (8 centres) and time to treatment
• Was part 2 only done because part 1 failed to deliver a significant outcome?
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Definitions
• Control event rate (CER) = C/(C+D)= outcome event rate in control group
• Experimental event rate (EER) = A/(A+B) = outcome event rate in experimental group
OutcomePositive Negative
ExposurePositive A BNegative C D
![Page 12: Tissue Plasminogen Activator for Acute Ischemic Stroke National Institute of Neurological Disorders and Stroke rt-PA Stroke Study Group.](https://reader030.fdocuments.us/reader030/viewer/2022032607/56649ed15503460f94be01ba/html5/thumbnails/12.jpg)
Definitions
• Control event rate (CER) = C/(C+D)• Experimental event rate (EER) = A/(A+B)
• Absolute risk reduction (ARR) = CER-EER• Relative risk (RR) = EER/CER• Relative risk reduction (RRR) = (CER-EER)/CER
Outcome
Positive Negative
ExposurePositive A B
Negative C D
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Definitions
• Number needed to treat (NNT)– The number of subjects that must be treated with
the intervention, compared with the control, for one extra subject to experience the beneficial effect.
– NNT = 1/ARR
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Definitions
• Control event rate (CER) = C/(C+D)• Experimental event rate (EER) = A/(A+B)
• Absolute risk reduction (ARR) = CER-EER• Relative risk (RR) = EER/CER• Relative risk reduction (RRR) = (CER-EER)/CER• Number needed to treat (NNT) = 1/ARR
Outcome
Positive Negative
ExposurePositive A B
Negative C D
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Bonus Points
• Using the numbers given for the Barthel index in part 2 of the study (Table 4), calculate the number needed to treat (NNT) in order to get a favourable functional outcome.
• Absolute risk reduction = 50-38 =12%• NNT= 1/ARR = 1/0.12 = 8.3
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Bonus Points
• Using the data given in Table 6, calculate the overall number needed to harm (NNH) for symptomatic intracranial haemorrhage (parts 1 and 2 of the study combined).
• Risk of symptomatic intracranial haemorrhage– t-PA group = (8+12)/(144+168) = 0.064 = 6.4%– Placebo = (0+2)/(147+165) = 0.006 = 0.6%
• Absolute risk reduction = 6.4-0.6 = 5.8%• NNH = 1/ARR = 1/0.058 = 17.2
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• Further analysis of stroke thrombolysis:www.thennt.com/thrombolytics-for-stroke/