Effect of treatment delay, age, and stroke severity on the effects of intravenous thrombolysis with alteplase for …

Posted: Published on August 6th, 2014

This post was added by Dr Simmons

Background

Alteplase is effective for treatment of acute ischaemic stroke but debate continues about its use after longer times since stroke onset, in older patients, and among patients who have had the least or most severe strokes. We assessed the role of these factors in affecting good stroke outcome in patients given alteplase.

We did a pre-specified meta-analysis of individual patient data from 6756 patients in nine randomised trials comparing alteplase with placebo or open control. We included all completed randomised phase 3 trials of intravenous alteplase for treatment of acute ischaemic stroke for which data were available. Retrospective checks confirmed that no eligible trials had been omitted. We defined a good stroke outcome as no significant disability at 36 months, defined by a modified Rankin Score of 0 or 1. Additional outcomes included symptomatic intracranial haemorrhage (defined by type 2 parenchymal haemorrhage within 7 days and, separately, by the SITS-MOST definition of parenchymal type 2 haemorrhage within 36 h), fatal intracranial haemorrhage within 7 days, and 90-day mortality.

Alteplase increased the odds of a good stroke outcome, with earlier treatment associated with bigger proportional benefit. Treatment within 30 h resulted in a good outcome for 259 (329%) of 787 patients who received alteplase versus 176 (231%) of 762 who received control (OR 175, 95% CI 135227); delay of greater than 30 h, up to 45 h, resulted in good outcome for 485 (353%) of 1375 versus 432 (301%) of 1437 (OR 126, 95% CI 105151); and delay of more than 45 h resulted in good outcome for 401 (326%) of 1229 versus 357 (306%) of 1166 (OR 115, 95% CI 095140). Proportional treatment benefits were similar irrespective of age or stroke severity. Alteplase significantly increased the odds of symptomatic intracranial haemorrhage (type 2 parenchymal haemorrhage definition 231 [68%] of 3391 vs 44 [13%] of 3365, OR 555, 95% CI 401770, p<00001; SITS-MOST definition 124 [37%] vs 19 [06%], OR 667, 95% CI 4111084, p<00001) and of fatal intracranial haemorrhage within 7 days (91 [27%] vs 13 [04%]; OR 714, 95% CI 3981279, p<00001). The relative increase in fatal intracranial haemorrhage from alteplase was similar irrespective of treatment delay, age, or stroke severity, but the absolute excess risk attributable to alteplase was bigger among patients who had more severe strokes. There was no excess in other early causes of death and no significant effect on later causes of death. Consequently, mortality at 90 days was 608 (179%) in the alteplase group versus 556 (165%) in the control group (hazard ratio 111, 95% CI 099125, p=007). Taken together, therefore, despite an average absolute increased risk of early death from intracranial haemorrhage of about 2%, by 36 months this risk was offset by an average absolute increase in disability-free survival of about 10% for patients treated within 30 h and about 5% for patients treated after 30 h, up to 45 h.

Irrespective of age or stroke severity, and despite an increased risk of fatal intracranial haemorrhage during the first few days after treatment, alteplase significantly improves the overall odds of a good stroke outcome when delivered within 45 h of stroke onset, with earlier treatment associated with bigger proportional benefits.

UK Medical Research Council, British Heart Foundation, University of Glasgow, University of Edinburgh.

See the original post:
Effect of treatment delay, age, and stroke severity on the effects of intravenous thrombolysis with alteplase for ...

This entry was posted in Uncategorized. Bookmark the permalink.

Comments are closed.