Thrombolysis After 3 Hours in Stroke Needs an others review
Current guidelines on giving thrombolysis 3 to 4.5 hours after stroke onset is based on uncertain evidence, and there needs to be urgent reconsideration of the available data to guides.
The review the British Medical Journal on March 17, is authored by a team led by Brian Alper, MD analyzing all the available data, tPA [tissue plasminogen activator] after 3 hours for stroke patients may not be of any benefit but has a definite risk of fatal bleeding.
He pointed out that most guidelines on tPA in stroke recommend its use up to 4.5 hours after symptom onset, including those by the American Heart Association/American Stroke Association (AHA/ASA), which give tPA a Class 1 recommendation in this time window, but he says the data do not justify such recommendations.
Other societies give weaker recommendations but the latest guidelines of the Canadian Association of Emergency Physicians give a weak recommendation against use of tPA after 3 hours. They are recognizing the uncertainty of the benefit and the greater consistency in harm.
Unless and until there are data showing unequivocal benefits to outweigh known harms, we believe that there should not be any strong recommendation or encouragement for the use of alteplase beyond 3 hours after stroke.
Data uncertaints in the results of both trials of tPA in the 3- to 4.5-hour time window in stroke the ECASS-3 suggested benefit in this time period, but there were baseline differences between the two groups: namely that the placebo group had a higher rate of previous stroke. In an analysis of only those patients who had not had a previous stroke, the results are no longer significant, and the overall difference between tPA and placebo was much smaller and the other trial IST-3 actually shows a trend toward harm with tPA given after 3 hours.
This was reported to be nonsignificant but the researchers used 99% confidence intervals for this analysis, which was not in the statistical analysis plan, It is traditional to use 95% confidence intervals for such analyses, and when this is done this result becomes significant for harm.
Cochrane review and a meta-analysis of individual-patient data, both published in 2014 and suggesting benefit of tPA in the 3- to 4.5-hour window and neither of these papers gave a clear accurate summary for tPA given between 3 and 4.5 hours which is supported by the data.
The trouble is that the data reported in the trial publications does not always match the conclusions reached, then there are new reviews of the trials which summarize the conclusions, which can compound any misunderstanding or errors made in translation.