Thrombolysis debate: Almost always versus almost never
Can clot retrievers and other forms of mechanical endovascular therapy (EVT) be at least as effective as thrombolysis?
Intravenous thrombolysis (IVT) has been the cornerstone of acute stroke treatment since alteplase was approved by the Food and Drug Administration in 1996. But that cornerstone began to erode in 2015 with the publication of multiple trials showing that clot retrievers and other forms of mechanical endovascular therapy (EVT) could be at least as effective as thrombolysis.
“We have had a number of trials in the last year or so asking what happens if you withhold routine medical treatment, thrombolysis, and go straight to endovascular?” said Michael D. Hill, MD, MSc, FRCPC, professor of clinical neuroscience and Hotchkiss Brain Institute at the Cumming School of Medicine, University of Calgary & Foothills Medical Center in Calgary, Canada.
It looks like the results are very slightly in favor of giving thrombolysis as well as endovascular treatment, but not by much, Dr. Hill said.
So, the question arises, should you withhold thrombolysis?
“And then it gets to more nuanced things like how much does it cost? Is it cost-effective? What about transport? Is endovascular therapy available where the patient is right now? What if you have a distal thrombus, or you can’t get access?”
Dr. Hill will argue that IVT should be given to all eligible patients pre-thrombectomy during “Cocktails Anyone? Intravenous Thrombolysis Symposium” 9-10:30 a.m. CST on Wednesday, Feb. 9.
Yvo Roos, MD, PhD, professor of neurology at the University of Amsterdam Academic Medical Center in Amsterdam, The Netherlands, will turn a more skeptical eye to the idea that IVT should continue as the mainstay of acute stroke treatment. His take: Fall back on IVT thrombolysis only when EVT is not immediately available on-site.
The obvious concern is adverse events. Multiple clinical trials have shown that IVT can carry a notably elevated risk of bleeding compared to EVT, at least in some patient populations.
And cost can be an enormous issue, depending on the patient and the location.
Alteplase costs about 16 times more in the United States than it does in India, Dr. Hill noted, and about eight times more in the U.S. than in Australia. The growing use of tenecteplase, which is generally less expensive than alteplase, could also change cost-effectiveness calculations for IVT and treatment decisions.
There is also the question of having sufficient EVT patient volume to contribute to physician expertise. EVT outcome can be highly dependent on operator experience and expertise, much like outcomes from coronary bypass grafting or any other surgical procedure. High volume centers tend to have better outcomes than lower volume centers. And while high volume stroke centers are more concentrated in urban areas, stroke patients are more broadly distributed. If the only EVT center with reasonable reach does relatively few procedures, Dr. Hill noted, do you really want to forego IVT?
“If the door to a major center is an hour or two away, it makes sense to give IVT in the primary center so the patient is already in treatment while they are in transit to that tertiary center for potential EVT,” Dr. Hill said. “People, and stroke patients, are widely distributed, whereas high volume stroke centers are not.”
The key, he added, is understanding both sides of the IVT-EVT debate to better evaluate the most appropriate approach for each patient.
“On average, it’s pretty even whether you do or don’t use thrombolysis,” he said. “But no individual patient is average. We will be arguing the subtle nuances, and it’s those nuances that are going to help you make the individualized decision.”
