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Tissue Plasminogen Activator for Acute Ischemic Stroke

Tissue Plasminogen Activator for Acute Ischemic Stroke. National Institute of Neurological Disorders and Stroke rt -PA Stroke Study Group. Summarise the paper in 200 words. Summarise the paper in 200 words. Aims

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Tissue Plasminogen Activator for Acute Ischemic Stroke

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  1. Tissue Plasminogen Activator for Acute Ischemic Stroke National Institute of Neurological Disorders and Stroke rt-PA Stroke Study Group

  2. Summarise the paper in 200 words

  3. 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

  4. 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)

  5. 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)

  6. 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.

  7. Abstract

  8. The Good... • Multi-centre RCT • Clear power calculation performed • Few patients lost to follow up • Intention to treat analysis

  9. 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)

  10. 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?

  11. 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

  12. 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

  13. 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

  14. 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

  15. 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

  16. 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

  17. Further analysis of stroke thrombolysis: www.thennt.com/thrombolytics-for-stroke/

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