All Hail n-tPA! [April Fools]

As much of a naysayer I’ve been over the past few years, holding out as a skeptic, waiting for a study to finally settle the issue on thrombolytics in acute ischemic stroke – that day has come.

Except, it’s not tPA.  It’s a novel isoform of tPA, dissimilar to all of the versions we’re familiar with – alteplase, desmoteplase, tenecteplase, etc.  The novel effect seems to be, according to these authors, related to cross-linking between n-tPA molecules rather than the intrinsic structure of the molecule itself, in which the n-tPA forms a sort of fibrinolytic meshwork.  The best conceptual physiologic analogy is probably phagocytosis, in which the intracerebral obstruction is more devoured than lysed.  As a result, outcomes appear to be dramatically improved – both in terms of efficacy and safety.

These authors describe the first phase of a single-center dose-finding study in which ischemic stroke patients otherwise meeting criteria for tPA were given 0.8 mg/kg, 1.2 mg/kg, or 1.6 mg/kg of n-tPA.  All patients had demonstrable arterial occlusion on CT angiography prior to administration.  Recanalization, as measured by repeat angiography, was 40%, 70%, and 70% in each cohort – with zero cases of intracranial hemorrhage or neurologic deterioration.

In the second phase, the authors expanded the protocol to randomize 200 patients either to tPA or n-tPA at the 1.6 mg/kg dose.  Unfortunately, they only report functional outcomes at hospital discharge, rather than the typical long-term follow-up of contemporary stroke studies.  That said, at discharge, 59% of n-tPA patients achieved favorable outcome, mRS 0-1, compared with 28% of the usual care group.  Rates of sICH were 1% in the n-tPA cohort compared with 4.5% in usual care.

As with all relatively preliminary data – and coming from a single-center – these results should be treated with caution.  But, has the impossible happened?  Has the day finally come where I can enthusiastically support the use of thrombolytics in stroke?

“Dose-Ranging and Outcomes Using a Novel Tissue Recombinant Activator in Acute Ischemic Stroke”
http://bit.ly/1acPEXp