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Why We Give tPA in Stroke

April 22, 2017


On the Shoulders of Giants

I want to believe…
Much has been written about NINDS.  This was the trial that gave the go-ahead to the current practice of thrombolytic therapy for acute ischemic stroke if given within 3 hours.  It was a 2-part study.  The first part enrolled 291 patients and found no improvement at 24 hours but improved outcome at 3 months.  The second part of the study enrolled 333 patients and found an increased odds of favorable outcome at 3 months, with 30% more patients having minimal or no disability at 3 months than the placebo group, NNT = 8.  But the rate of intracerebral hemorrhage was 6.4% in the tPA group and 0.6% in the placebo group, NNH = 17.

A recent meta-analysis found that thrombolysis for acute stroke was effective at improving functional outcome but came at the cost of increased risk of intracranial hemorrhage and early mortality.  Patients and families deserve an even-handed presentation of the risks and benefits when giving informed consent.  This figure was especially helpful in visualizing that.

Hat tip to Dr. Umana for the tweet and to AAEM for the figure. Click figure for the full AAEM statement on tPA in stroke.

Hat tip to Dr. Umana for the tweet and to AAEM for the figure. Click figure for the full AAEM statement on tPA in stroke.

Spoon Feed
Use of tPA within 3 hours for acute ischemic stroke improved functional outcome at 3 months but increased early risk for intracranial hemorrhage.  You need to know this study, so here are some suggested resources to get you started.

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N Engl J Med. 1995 Dec 14;333(24):1581-7.

Tissue plasminogen activator for acute ischemic stroke. The National Institute of Neurological Disorders and Stroke rt-PA Stroke Study Group.

[No authors listed]

Comment in



Thrombolytic therapy for acute ischemic stroke has been approached cautiously because there were high rates of intracerebral hemorrhage in early clinical trials. We performed a randomized, double-blind trial of intravenous recombinant tissue plasminogen activator (t-PA) for ischemic stroke after recent pilot studies suggested that t-PA was beneficial when treatment was begun within three hours of the onset of stroke.


The trial had two parts. Part 1 (in which 291 patients were enrolled) tested whether t-PA had clinical activity, as indicated by an improvement of 4 points over base-line values in the score of the National Institutes of Health stroke scale (NIHSS) or the resolution of the neurologic deficit within 24 hours of the onset of stroke. Part 2 (in which 333 patients were enrolled) used a global test statistic to assess clinical outcome at three months, according to scores on the Barthel index, modified Rankin scale, Glasgow outcome scale, and NIHSS:


In part 1, there was no significant difference between the group given t-PA and that given placebo in the percentages of patients with neurologic improvement at 24 hours, although a benefit was observed for the t-PA group at three months for all four outcome measures. In part 2, the long-term clinical benefit of t-PA predicted by the results of part 1 was confirmed (global odds ratio for a favorable outcome, 1.7; 95 percent confidence interval, 1.2 to 2.6). As compared with patients given placebo, patients treated with t-PA were at least 30 percent more likely to have minimal or no disability at three months on the assessment scales. Symptomatic intracerebral hemorrhage within 36 hours after the onset of stroke occurred in 6.4 percent of patients given t-PA but only 0.6 percent of patients given placebo (P < 0.001). Mortality at three months was 17 percent in the t-PA group and 21 percent in the placebo group (P = 0.30).


Despite an increased incidence of symptomatic intracerebral hemorrhage, treatment with intravenous t-PA within three hours of the onset of ischemic stroke improved clinical outcome at three months.

PMID: 7477192 [PubMed – indexed for MEDLINE]

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