Rather – as I’ve said before – it simply doesn’t work the way we’ve been taught.
The core concepts of the theoretical utility of tPA for ischemic stroke are demonstrated nicely in the new endovascular trials. Patients do well, better than the natural course of their disease if:
- There is significant viable brain distal to the vascular occlusion as a result of collateral circulation.
- The vessel is rapidly and reliably opened.
Both these criteria were met in the new endovascular trials, requiring imaging evidence of a small infarct core and use of modern retrieval devices. However, the broad population being pushed as candidates for tPA are not as fortunate – the key feature being the abysmal recanalization rate of tPA, only 46% in a meta-analysis of tiny case series from mostly the ‘90s. Comparatively, in the same report, early spontaneous recanalization was present in 24%. So, obviously, there’s only even a 1 in 5 chance a patient will receive an additive benefit from tPA for recanalization – which, with some heterogeneity, means our NNT has a maximum upper bound if we treat an unselected population of all-comers.
This study is a small case series from the ongoing PRove-IT study, looking specifically at, essentially, the permeability of intracranial thrombi. These authors hypothesized this might be an important predictor of recanalization because, after all, if there’s no flow through an impermeable occlusion, tPA can never fully contact the substrate of interest. These authors used CT angiography to estimate occult anterograde flow versus retrograde flow, and followed-up recanalization following tPA.
There are only 66 patients in this small observational study, but the results are rather compelling. They estimated 17 (25.8%) of patients had some minimal anterograde flow through the occluded vessel. These patients, with some detectable flow, had a 66.7% recanalization rate. Conversely, the 49 patients without any residual anterograde flow had a recanalization rate of only 29.7% – a rate not dissimilar to spontaneous. And, outcomes followed recanalization – logically, considering detectable anterograde flow and effective destruction of the occlusion are highly favorable features.
The moral of the story? It’s quite clear there are promising venues for determining which patients have the best chance to benefit from tPA – and those for whom the harms exceed those chances. The perpetual “tPA for all!” call being added to guidelines and quality measures is a product of conflict-of-interest and corporate sponsorship, not good medicine – and we can do better, if we simply cared to investigate.
“Occult Anterograde Flow Is an Under-Recognized But Crucial Predictor of Early Recanalization With Intravenous Tissue-Type Plasminogen Activator”