This independent literature review will inform revision of ACEM’s Statement on Intravenous Thrombolysis for Ischaemic Stroke (S129), to be undertaken in 2016. This is likely to support use of thrombolysis for treatment of ischaemic stroke (a significant change from the previous ACEM statement on this topic).
From the Executive Summary and abstract:
- Thrombolytic therapy (with rTPA) administered within 4.5 hours of ischaemic stroke increased the proportion of participants who were essentially back to baseline, as assessed by a modified Rankin Score (mRS) score of 0-1, at 90 days after stroke (odds ratio (OR) 1.58, 95% confidence interval (CI) 1.26 to 1.99). Evidence from the National Institute of Neurological Disorders and Stroke (NINDS) studies indicates that this benefit is sustained in the longer term, i.e. 12 months after treatment (OR=1.7, 95% CI= 1.2 to 2.3).
- Treatment within 3 hours of stroke (OR=1.85, 95%CI=1.38 to 2.47), provided a greater advantage for a return to independence (mRS 0-1) than treatment between 3-4.5 hours (OR=1.27, 95%CI=1.01 to 1.60). Timing of treatment within the three hour window had little impact on mortality rates.
- Numbers needed to treat (NNT) to achieve functional benefits, as measured by mRS outcome of 0-1, was 10 (i.e. 10 patients needed treatment for one additional good functional outcome).
- Timing of administration alters numbers needed to treat to benefit (NNTB), with around half the number of patients needing to be treated for one to benefit at 3 hours (NNTB = 7, 95% CI = 14 to 5), compared to treatment at 3-4.5 hours (NNTB = 18, 95% CI = 419 to 9).
- There was no statistical difference in outcomes in the proportion of patients who were independent, as assessed by a mRS of 0-2 (OR=1.21, 95% CI=0.98 to 1.50). A mRS of 2 implies slight disability but able to look after own affairs without assistance.
- Treatment with Alteplase increased the odds of symptomatic intracranial haemorrhage (sICH) during the first week to 10 days following treatment (OR=6.90, 95%CI=2.21 to 21.50) and early death from intracranial haemorrhage (ICH) (OR=7.39, 95% CI=1.93 to 28.29) However heterogeneity in the safety data suggests caution should be applied in the interpretation of these results.
- Numbers needed to harm (NNTH) was 42 for symptomatic intracranial haemorrhage (i.e. 42 patients needed treatment for one to experience sICH), however, with very large confidence intervals (13-119).
- 122 (95% CI = 830 to 30) would need to be treated for one patient to die from ICH.
- The large confidence intervals around these figures should be borne in mind when interpreting the NNT.
- Overall the risk of death at 30 days is no different if given thrombolysis or not. Whilst there is a much larger number of symptomatic intra cranial haemorrhages in those patients given thrombolysis, in the non-thrombolysis group the rate of death was the same.
- Demographic factors were examined and found no evidence that any of sex, age, ethnicity and comorbidities were predictive of patients who may respond better to rTPA.
- There is evidence that thrombolytic therapy increases the proportion of patients who were back to baseline (mRS 0-1) at 90 days after stroke, however, at a cost of increased intracranial symptomatic haemorrhage.
- A mRS of 2 implies slight disability but able to look after own affairs without assistance. If patients are willing to accept this as an outcome from their stroke, there is no evidence that thrombolysis offers any benefits but still carries a significant risk of symptomatic intracranial haemorrhage.
- Therefore, discussion with patient and family/carers by the treating clinicians, and informed consent is vital to any decision about use of thrombolytic therapy in stroke.
Dr Danny Ben-Eli, BSc, MD, FACEM