The EndOfLitOfNote [April Fool’s]

Over the last five years, Emergency Medicine Literature of Note has grown from quite inauspicious origins to something more – with a readership greater than just my mom.

Of course, as is constant in nature, all things must end.

Today will be the final post of EMLitOfNote in its current form.  While my academic and other non-profit affiliations have either encouraged or tolerated the blog, my newest endeavor means my public-record skeptical combativeness must cease.

In partnership with Genentech, Covidien, and the American Stroke Association, I will be joining a new project – the SMart StrOKE IniTiative (SMOKE-IT).  Rather than focusing on the flaws and conflict-of-interest in the new stroke literature, I’ve been asked to consult on pre-publication messaging to prevent such naysayers as myself from nitpicking the inconsequential details.

Even though EMLitOfNote provides commentary on all disciplines of work, the legal team associated with this new partnership feels this site is best discontinued.  While it seems, frankly, unfair, this new project provides me with generous enough compensation that I am somehow able to cope.

You can read the press release here:

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”