Correspondence
Thrombolysis in acute stroke See Editorial page 1366
1394
In their meta-analysis of intravenous thrombolysis with alteplase for acute ischaemic stroke, Jonathan Emberson and colleagues (Nov 29, p 1929)1 concluded that the increased risk of early death from intracranial haemorrhage in patients taking alteplase was offset by an increase in disability-free survival. This interpretation gives the impression that the high level of mortality in the acute phase tends to diminish with time, but that is not the case. In the latest Cochrane analysis of thrombolysis for acute ischaemic stroke, 2 thrombolysis gave no survival advantage between 7 days after thrombolysis and the end of follow-up. The only study that has shown a survival advantage for thrombolysis in such a time interval was IST-3,3 a randomised controlled trial, which incidentally showed no benefit with respect to its primary outcome (proportion of patients alive and independent). Stroke patients, irrespective of treatment, have a relatively high mortality after the acute phase. A relatively large percentage difference between treatment and control groups will therefore gradually diminish. Such dilution of a security measure cannot be held in favour of the treatment. Instead, the primary endpoint should be compared with a reliable security measure, ie, short-term mortality. The findings of a 2012 meta-analysis4 of thrombolysis for acute ischaemic stroke indicated a 9·0% absolute increase (40·7% vs 31·7%, hazard ratio 1·53, 95% CI 1·26–1·86, p4·5 h
2·0%*
50*
*Not significant.
Table: Absolute risk reduction and number needed to treat by alteplase treatment delay
www.thelancet.com Vol 385 April 11, 2015
*Mattias Brunström, Bo Carlberg [email protected] Department of Public Health and Clinical Medicine, Umeå University, Umeå, Sweden 1
Emberson J, Lees KR, Lyden P, et al. Effect of treatment delay, age, and stroke severity on the effects of intravenous thrombolysis with alteplase for acute ischaemic stroke: a meta-analysis of individual patient data from randomised trials. Lancet 2014; 384: 1929–35.
I read with interest the meta-analysis by Jonathan Emberson and colleagues,1 but would have appreciated heterogeneity assessments for the major outcomes in the meta-analysis. The validity of any meta-analysis depends on the underlying clinical and statistical heterogeneity. 2 If clinical heterogeneity is substantial (ie, clinical features, such as setting, disease spectrum, or populations studied are highly variable), or if statistical heterogeneity suggests that results are affected by more than chance (typically p
Thrombolysis in acute stroke See Editorial page 1366
1394
In their meta-analysis of intravenous thrombolysis with alteplase for acute ischaemic stroke, Jonathan Emberson and colleagues (Nov 29, p 1929)1 concluded that the increased risk of early death from intracranial haemorrhage in patients taking alteplase was offset by an increase in disability-free survival. This interpretation gives the impression that the high level of mortality in the acute phase tends to diminish with time, but that is not the case. In the latest Cochrane analysis of thrombolysis for acute ischaemic stroke, 2 thrombolysis gave no survival advantage between 7 days after thrombolysis and the end of follow-up. The only study that has shown a survival advantage for thrombolysis in such a time interval was IST-3,3 a randomised controlled trial, which incidentally showed no benefit with respect to its primary outcome (proportion of patients alive and independent). Stroke patients, irrespective of treatment, have a relatively high mortality after the acute phase. A relatively large percentage difference between treatment and control groups will therefore gradually diminish. Such dilution of a security measure cannot be held in favour of the treatment. Instead, the primary endpoint should be compared with a reliable security measure, ie, short-term mortality. The findings of a 2012 meta-analysis4 of thrombolysis for acute ischaemic stroke indicated a 9·0% absolute increase (40·7% vs 31·7%, hazard ratio 1·53, 95% CI 1·26–1·86, p4·5 h
2·0%*
50*
*Not significant.
Table: Absolute risk reduction and number needed to treat by alteplase treatment delay
www.thelancet.com Vol 385 April 11, 2015
*Mattias Brunström, Bo Carlberg [email protected] Department of Public Health and Clinical Medicine, Umeå University, Umeå, Sweden 1
Emberson J, Lees KR, Lyden P, et al. Effect of treatment delay, age, and stroke severity on the effects of intravenous thrombolysis with alteplase for acute ischaemic stroke: a meta-analysis of individual patient data from randomised trials. Lancet 2014; 384: 1929–35.
I read with interest the meta-analysis by Jonathan Emberson and colleagues,1 but would have appreciated heterogeneity assessments for the major outcomes in the meta-analysis. The validity of any meta-analysis depends on the underlying clinical and statistical heterogeneity. 2 If clinical heterogeneity is substantial (ie, clinical features, such as setting, disease spectrum, or populations studied are highly variable), or if statistical heterogeneity suggests that results are affected by more than chance (typically p
