tPA in CVA: Blood, Sweat and Tears
Oh yes, Conference Journal Club will be a duel this week, featuring two chiefs – nearing retirement, holding back nothing, fighting for their honor and their patients' cortex… Heads will roll.
Marc's paper is available here — it's a classic, the NINDS trial from 1995 (NEJM 333:1581-1587), predating Marc's arrival at Sinai (which historians believe occurred sometime during Clinton's second term). Many of the interns were still in high school in 1995, but otherwise, pretty much nothing has changed in medicine.
Marc's discussion brought up a few key points about this landmark paper. Yes, tPA was shown to be helpful for mild stroke (numbers to follow). It was also shown to greatly increase the risk of devastating side effects. This was under the best of circumstances — neuroradiologists reading the films, stroke teams and NIH folks hovering over the case… in the "real world" or community setting, timing will be slower, neuroradiologists may not be available, and the patient may not be able to vocalize one of the dozen or so contraindications to tPA in their history.
It's worth remembering that, even in the idealized setting of the NINDS trial, the NNT (# needed to treat) for tPA was 8, the NNH (harm) was 17. So, essentially, for every 2 good outcomes you can attribute to tPA, there will be one bad outcome. I think that's a good way to think of thrombolytics in stroke, and maybe even a good way to explain it to patients.
For completeness sake, here's an excerpt from the ACEP statement on thrombolytics for stroke (note, this is not a clinical guideline, but rather a 2002 policy statement):
- Intravenous tPA may be an efficacious therapy for the management of acute ischemic stroke if properly used incorporating the guidelines established by the National Institute of Neurological Disorders and Stroke (NINDS).1
- There is insufficient evidence at this time to endorse the use of intravenous tPA in clinical practice when systems are not in place to ensure that the inclusion/exclusion criteria established by the NINDS guidelines for tPA use in acute stroke are followed. Therefore, the decision for an ED to use intravenous tPA for acute stroke should begin at the institutional level with commitments from hospital administration, the ED, neurology, neurosurgery, radiology, and laboratory services to ensure that the systems necessary for the safe use of fibrinolytic agents are in place.
Also, as ever,there's a great page summarizing stroke literature, already up at emcrit.org…
Posted
on Tuesday, June 6th, 2006 at 11:05 am by Nick. Filed under
Stroke / TIA, Journal Club.
You may post a comment.
Great post Nick, exactly what I would say if I was a smart as you. Something I really wanted to emphasize in my talk was that the exclusion criteria should always be strictly followed, esp. time of symptom onset and blood pressure control…it can be inferred from the follow up observational trials in the “real world” (Cleveland area study in JAMA) that protocol violations were likely the reason behind the higher rates of bleeding noted.
Yes, I’m old-school Sinai and I’m sad to leave. Rent Hannah and Her Sisters tonight; there is one scene in the movie where Woody Allen thinks he has a brain tumor and has his workup done at MSH…he walks out of the “old” Guggenheim Pavilion onto 5th Ave! See you on the other side…
–marc
Comment by andrem04 on June 17th, 2006 at 1:26 am