Yet again, the tPA apologists dip into their bag of registry data in an attempt to defend tPA – and end up contradicting themselves.
In 2009, neurologists in India published a retrospective case series examining the outcomes following tPA at their institution. Specifically, they divided up the cases between those with arterial occlusion present on CT angiogram of the cerebral vessels, and those with no demonstrated arterial occlusion. For patients with demonstrated occlusion, there were significant differences in early NIHSS improvement favoring tPA, but no long term mRS improvements. Conversely, there were 119 without occlusion present – and the early NIHSS improvement and late mRS improvement outcomes were similar. There were, however, substantial baseline differences between those receiving tPA and those who did not – and retrospective studies are confounded by many biases – but there was at least a suggestion that some stroke subtypes might not benefit from tPA.
Clearly, that did not sit well with the authors of this study, a handful of whom are paid representatives of Boehringer Ingelheim. They performed their own retrospective review of a multi-center registry to evaluate outcomes of patients without arterial occlusion demonstrated on initial angiography, but definitive acute stroke seen on follow-up MRI. They also further subdivided stroke subtypes into lacunar (subcortical, thalamic, and pontine infarct <20mm) vs. non-lacunar (all others).
They identified 154 non-lacunar strokes, 49 of whom underwent thrombolysis, and 102 lacunar strokes, 54 of whom underwent thrombolysis. Outcomes favored tPA for non-lacunar stroke syndromes, with 51% of tPA patients mRS 0-1 at 90 days, compared with 30% for those who did not receive tPA. Symptomatic intracranial hemorrhage occurred in 6.1% of tPA patients, compared with 1% without. Lacunar strokes, however, had identical 90 day mRS outcomes – 65% vs. 63%. For lacunar strokes, sICH occured in 3.7% of tPA patients vs. 0% without. The authors still try to statistically adjust their way out of this equivalency for the primary outcome – but fail.
So, again, this is a retrospective study confounded by many biases. However, the authors have nicely demonstrated support for a hypothesis some stroke subtypes – particularly those for whom no arterial occlusion is demonstrated on angiography – might not benefit from tPA. Thus, the conclusion:
“In conclusion, this retrospective study demonstrates the efficacy of intravenous thrombolysis in patients with ischemic stroke who have no radiographically demonstrated arterial occlusion at presentation. Both subgroups, nonlacunar and lacunar strokes, were found to have had better clinical outcome after receiving r-tPA.”
Or, the opposite of what their data suggests.
Is it really so impossible conceive tPA might not be magical?
“Thrombolysis in Ischemic Stroke Without Arterial Occlusion at Presentation”
Dr. Radecki – You've morphed into a zealot about this topic. You highlight "meta analyses" like the BMJ's as it suits your belief & agenda, yet regarding the above studies you completely discredit them? The 'no occlusion' study is small but to anyone reading it through balanced lenses it does prompt one to think that imaging is not as important as what might be going on in the brain's vascalature. TPA or retaplase lyse fibrin, we know that. The sugggestion that even in the absence of clot on imaging there is a benefit by giving this agent "fits" with the broader literature thematically. I am tired of reading about the conflicts of iterest that many highlight now as certain exclusionary factors. Every drug we give was studied in trials that had sponsors. This logic you apply reveals a sense of desperation, not strength and confidence.
JMD
Hm.
While I tend to respect your opinion regarding the characterization of my attitude towards tPA, I'm afraid you've lost me a little bit on the details. Indeed, I tend to think – as far as the spectrum of pro- and con- bias, I'm fairly accepting of tPA. However, the alternative extreme – the massive expansion of tPA to all subgroups is based just as tenuously on "belief", and articles like this are examples of the selective reporting of the cross-section of results supporting their view.
And, you're correct – many drugs we give were studied in trials with sponsors. And, many of these drugs have been found to have under-reported harms or lack of benefit upon subsequent study (see: RE-LY, still somehow finding additional bleeding events, five years later).