… taking a quick break from combating misinformation in our age of public health emergency to note this important non-COVID-19 article from the New England Journal of Medicine. Today’s question: is alteplase necessary prior to endovascular thrombectomy in acute ischemic stroke?
“It depends”.
This isn’t the first study to hit the light of day, but the largest. Previously, the “Randomized Study of Endovascular Therapy with Versus Without Intravenous Tissue Plasminogen Activator in Acute Stroke with ICA and M1 Occlusion (SKIP)” was presented at the International Stroke Conference earlier this year. Their study enrolled 204 patients and found no clinically important differences, particularly with respect to their primary outcome of mRS 0-2. Symptomatic intracranial hemorrhage was increased by a couple percent in those with bridging therapy, and there was a small excess of deaths – but, of course, none of these were “statistically significant”.
This study is three times the size, with 656 enrolled. Specifically, these are patients with large-vessel, anterior circulation occlusions for whom treatment can be initiated within 4.5 hours – the role for which alteplase is currently enshrined in the guidelines. And, these results are remarkably consistent with the prior observations. The mRS scores were, again, virtually identical. There was, again, an 2% absolute increase in sICH favoring the direct to endovascular therapy group, likely contributing to an observed ~1% excess deaths in the alteplase cohort.
The only element in “favor” of alteplase bridging is the surrogate outcome of successful reperfusion. There was a 4.6% excess of successful reperfusion before thrombectomy in the alteplase cohort, an advantage maintained to final angiographic recanalization at 24-72 hours. However, this small difference simply has minimal reliable effect on clinical outcomes – reperfusion is not synonymous with tissue salvage.
The net result of these observations ought to be the exclusion of thrombolytic therapy prior to endovascular intervention for those patients with immediate catheterization lab availability. Many patients, however, have prolonged transport times prior to endovascular intervention, and this study does not address this situation. However, prior studies likely demonstrate tenecteplase is more effective at obtaining early reperfusion in patients with large vessel occlusion, and probably should be the thrombolytic of choice in a “drip and ship” situation – if not all situations.
At this point, at least, the onus ought to rather be on proving clinical advantage to alteplase/tenecteplase prior to endovascular intevention. Given the consistent costs and harms of thrombolytic therapy, it is time to prove its value, rather than the converse.
“Endovascular Thrombectomy with or without Intravenous Alteplase in Acute Stroke”
https://www.nejm.org/doi/full/10.1056/NEJMoa2001123