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Treating stroke: this year’s headlines

New evidence supports an alternative to IV tPA

November 2023

WHEN IT COMES to advances in managing stroke in the hospital, it’s been a pretty impressive couple of years. That’s according to S. Andrew Josephson, MD, chair of the neurology department at the University of California, San Francisco, speaking at UCSF’s fall 2023 hospital medicine conference.

Those advances are extending the timeline for treating ischemic strokes and identifying new therapies and management tools. Here’s one example: Thrombolysis with IV tPA has for years been the standard of care for patients with ischemic stroke, as long as it’s administered within 4.5 hours of symptom onset. But the thrombolytic tenecteplase (TNK) has emerged as an alternative to tPA. Multiple trials—including one published in The Lancet in June 2022—have found that TNK is just as effective and safe.

“I don’t think tenecteplase is necessarily more effective than IV tPA,” Dr. Josephson said. “It’s just more convenient.” That’s because IV tPA is given first as a bolus and then as a one-hour infusion.

“I don’t think tenecteplase is necessarily more effective than IV tPA. It’s just more convenient.”

S. Andrew Josephson, MD
University of California, San Francisco


“TNK is just one shot, and that’s important for transfer protocols,” Dr. Josephson said. In many parts of California, for instance, patients receiving an IV tPA drip need to have critical care transport to get to another hospital, “and that can be very challenging to find. With TNK, you give one shot and the patient can be transferred with a regular transport.”

That’s why, he pointed out, a growing number of hospitals over the last 24 months have adopted TNK protocols.

Expanding the embolectomy timeline 
When a patient first presents to the ED with a stroke, you need a noncontrast CT to make sure that patient is one of the 85% of stroke patients who have had an ischemic stroke, not a hemorrhagic one.

“In addition to a noncontrast CT, we do a couple of other types of imaging that in 2023 make a real difference,” Dr. Josephson said. One is a CT angiogram of both the head and neck vessels; the other is CT perfusion. “When you see a patient in the emergency department,” he explained, “you have no idea how many of their clinical symptoms are caused by dead or by salvageable tissue. That’s why perfusion is so important.”

In 2015, five large trials published in the New England Journal of Medicine all found that embolectomy with newer-generation devices really works for stroke patients who have a large vessel occlusion (LVO). A CT angiogram allows you to identify LVOs.

“In these trials, people got IV tPA first if they came in within four and a half hours and were eligible,” Dr. Josephson pointed out, “and all these embolectomy trials were for six hours. In 2023, if you’re within six hours of symptom onset and have a LVO identified on CTA, we take the clot out no matter whether you got tPA or not.”

Other advances that pushed the treatment timeline even further came in 2018 with the DAWN and the DEFUSE 3 trials. “Those showed that we could select patients who have LVOs for embolectomy beyond six hours all the way up to 24 hours, based on perfusion imaging,” Dr. Josephson explained. “If perfusion shows a lot of salvagable tissue you can save and very little dead tissue, you take the clot out and these patients do well. This is why perfusion-based imaging is now the standard of care for stroke patients.”

Dr. Josephson added that he now has two different apps on his phone that automate perfusion readings. “The software calculates how much tissue is dead and how much is at risk, and I don’t even need a neuroradiologist to weigh in on the perfusion to make initial decisions,” he said. “I get a readout within seconds of the scan being complete.”

For patients with an LVO who are between six and 24 hours post-symptom onset, Dr. Josephson said, “we use perfusion to decide who gets an embolectomy and who doesn’t.” (See ““Not ready for prime time … ,” below.)

Many hospitals, of course, aren’t equipped to remove brain clots onsite. “That’s the idea of comprehensive stroke centers,” he noted. “If your hospital doesn’t have a transfer protocol and an arrangement for where eligible patients can be sent for embolectomy, it probably should.”

At the same time, Dr. Josephson believes that hospitals—even rural ones—that transfer patients out for embolectomy should still consider perfusion-based imaging for stroke patients. “Then you have the information you need to decide whether to transfer patients with LVOs beyond the six-hour window of time.”

Long-term monitoring
For all patients with stroke, it’s important to figure out why they had a stroke to be able to decide on secondary prevention.

“We want to know where it came from,” said Dr. Josephson. Because of his hospital’s CT angiogram protocol, “I’ve already looked at the intracranial vessels, the carotids and the aortic arch. The only thing I need to work up in the hospital is to look at the heart with an echo of some sort and monitor if patients have A fib.”

Physicians used to look for A fib in stroke patients with just an EKG and 48 hours of telemetry. “But multiple studies supported monitoring for more than 21 days—and 30 days is now the standard—of continuous telemetry in patients who leave the hospital when you don’t know why they had a stroke or a TIA. One out of five of them will be found to have A fib, which clearly changes your management.”

Here’s another headline from the last 24 months, thanks to the STROKE AF trial published in 2021 and other newer studies: If after 30 days you still don’t know what caused a patient’s stroke, monitoring for 12 months with an implantable cardiac monitor detects A fib in about 12% of patients vs. only 1.8% of those receiving usual care without long-term monitoring.

“This may not be standard yet,” said Dr. Josephson, “but most of us in the stroke field are doing it.”

Not ready for prime time …

RECENT STUDIES offer intriguing hints of what might become standard care for stroke patients, although they aren’t there yet.

Speaking at UCSF’s fall 2023 hospital medicine conference, S. Andrew Josephson, MD, chair of the UCSF neurology department, cited a trial published in 2020 in the New England Journal of Medicine that examined not doing thrombolysis with IV tPA and going straight to embolectomy.

“If you’re at a hospital that can do embolectomy and the interventionalists are available, you may just want to skip the tPA because it takes too much time,” Dr. Josephson said. If the patient has to be transferred for the embolectomy or the interventionalist is offsite, however, “go ahead and give the tPA so you don’t lose any time.”

And the New England Journal of Medicine this year published two large trials that looked at embolectomy in large infarcts. “The question is: If there’s a ton of dead tissue, far beyond the amount of dead tissue that we usually treat, and only a little bit of salvagable, do patients benefit if we open up the clot?” Given that embolectomy is a very safe procedure, “it turns out that maybe there shouldn’t be too much of a barrier to this. Maybe preserving a few neurons is worth it.”

While more such studies are needed, “I think where we’re moving to is questioning whether there should be a limit to how much infarcted tissue we won’t treat,” said Dr. Josephson. Right now, however, “we use perfusion-based imaging to select.”

Phyllis Maguire is Executive Editor of Today’s Hospitalist.

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