Thrombolytics in Acute Stroke? Time is brain

According to this article in the September 25th edition of the New England Journal of Medicine, alteplase improves the outcomes in stroke patients up to 4.5 hours after symptom onset. Previously, the “window” of effectiveness was only three hours. The clinical trial criteria are here.

The percentage of patients having a favorable outcome at 90 days in this study wasn’t huge, but was statistically significant - 52% of patients receiving alteplase had good outcomes compared with 45% of patients who received placebo. At the same time 27% of patients had some type of bleeding after receiving thrombolytics compared with only 17% of patients who had bleeding after receiving placebo. The rate of symptomatic bleeding in the brain was 2.4% for thrombolytics versus 0.2% for placebo.

So while you may have an overall improvement in your outcome at 90 days if you get the medication, more than 1 in 4 patients who receive the medication will have bleeding and 1 in 40 patients will have symptomatic bleeding.

Is it worth the risk?

In the editorial article accompanying the study, one of the study authors states that “one cannot help wondering why thrombolytic therapy has traveled such a long, difficult path to wider clinical use.”

I can help wondering.

Thrombolytics are one of the few things that physicians can give that will have an immediate and significant harm on patients. Sure, patients may occasionally have bad outcomes from allergic events or they may have undesirable side effects from some medications. But 2.4% of patients will have symptomatic bleeding in their brains when they get thrombolytics. Some of those patients will die.
I like to pose this scenario to my trainees: a patient presents to you 30 minutes after the onset of a left hemispheric stroke; how long do you have to initiate thrombolytic therapy?
The correct answer is 1 minute, not 2.5 hours, and ECASS III does not now justify an answer of 4 hours. From the moment the patient arrives at the door, every minute counts, and the only justifiable delays would be for performing brain imaging studies to exclude hemorrhage and for obtaining the results of a few simple laboratory tests. In fact, the very real peril of the ECASS III data is that some may take an even more leisurely approach to treating acute stroke. Nothing could be more wrong, for as we look back on the past decade of thrombolytic therapy for stroke, it is very clear that our focus must remain on the door-to-needle time. Every minute matters during a stroke.

So the choice is …
1. Let patient continue with the stroke symptoms they have already presented with and follow the doctrine of “primum non nocere.” After all, even this study shows that if doctors do nothing, 45% of the patients will get better on their own.
-or-
2. Give a medication that may improve clinical outcome in 7% more of the patients … at the risk of getting a bad outcome from the medication.

What would you choose?

Want a simple way to immediately expand the use of thrombolytic therapy?

If an On Call physician gets a CT report from a radiologist that says “no bleed,” the patient meets the criteria for thrombolytic therapy and doesn’t have any exclusion criteria, then the Physician cannot be held liable for any bad outcomes for giving thrombolytics.

There will still be some that philosophically disagree with giving patients a medication that could kill them. Nevertheless, there would be an instant spike in thrombolytic use. I guarantee it.