With the publication of MR-CLEAN two days ago, the medical world (especially Covidien, Stryker, and Penumbra) is ready to throw out all previous neutral trials – MR-RESCUE, SYNTHESIS, IMS-3 – and rush headlong into endovascular therapy for acute ischemic stroke as a new standard of care.
Nonsense, you say? Not when financial and professional conflicts-of-interest coordinate to drown out the skeptics.
And, frankly, the reality is – despite trials failing to demonstrate benefit, endovascular therapy is already in widespread use. The underlying tissue-reperfusion hypothesis upon which thrombolytic therapy is predicated is too compelling to wait for proof of efficacy or effectiveness. Alas.
This is ICARO-3, essentially an ongoing prospective registry of patients considered by experts as optimal candidates for endovascular interventions. These are all proximal internal carotid artery occlusions, having the among the least favorable rates of recanalization with IV tPA alone. These authors obtained data on 324 cases between 2010 and 2013 receiving endovascular therapy and 324 matched controls (including 253 from the original ICARO study). The endovascular cohort included a distribution of patients who received intra-arterial lysis, mechanical retrieval, systemic thrombolysis, or a combination of those treatments, while the tPA cohort received systemic thrombolysis alone.
Patients were generally well-matched on baseline characteristics, with an overall median NIHSS of the entire cohort of 16. Ultimately, 18.2% of the IV tPA-only cohort had an mRS 0-1 at three months, compared with 20.7% of the endovascular cohort, and OR of 1.17 (95% CI 0.79-1.73). However, 37% of the endovascular cohort experienced intracranial bleeding of which 6% was fatal, compared with 17.3% and 2.2% in the tPA-only cohort. In summary, the outcomes – both positive and negative – were a wash. The authors try to splice out an adjusted subgroup of specific types of endovascular interventions with improved outcomes compared with controls, but these statistical calisthenics are best left unmentioned given their limited validity.
So, until MR-CLEAN, all the randomized trials for efficacy have been neutral. ICARO-3, a real-world effectiveness observation – also neutral.
Is it too late to derail the bandwagon?
“Intravenous thrombolysis or endovascular therapy for acute ischemic stroke associated with cervical internal carotid artery occlusion: the ICARO-3 study”
http://www.ncbi.nlm.nih.gov/pubmed/25451851
The problem I see in ICARO-3 is "intra-arterial lysis, mechanical retrieval, systemic thrombolysis, or a combination of those treatments" – it's a pretty heterogeneous treatment arm.
MR-CLEAN has the features I wanted for a good trial on this topic – the CT-A, the starting tPA in any case, the acceptable recanalisation success in the treatment arm.
But I have to admit that I want to believe mechanical recanalisation works for proximal clots. I'm probably biased.
Your observation is spot-on. And, if MR-CLEAN is replicated reliably, then yes – it's identified a specific subgroup of arterial occlusions for whom outcomes are dismal, but may be slightly less dismal after endovascular therapy.
The issue, unfortunately, is whether patients will be treated in the narrowest criteria like MR-CLEAN, or more broadly and heterogeneously, like ICARO-3?