Today’s big headlines in stroke care
Recent advances include an expanded timeline for IV tPA
Keywords: New research on stroke patients recommends antiplatelets, and expands the timeline for IV tPA
by Sara Jackson
Published in the April 2009 issue of Today's Hospitalist
The good news for hospitalists who treat stroke—and that’s just about all of you, according to a show of hands at a recent conference—is that several “very big headlines” from the last year or two translate into new tools and timelines to improve the treatment of acute ischemic stroke.
That’s according to S. Andrew Josephson, MD, director of the neurohospitalist program and assistant professor of neurology at the University of California, San Francisco (UCSF). Dr. Josephson examined these new studies and their importance for stroke care at last year’s UCSF annual hospital medicine
|“TIA is our version of unstable angina. It is our opportunity to intervene and really make a difference.”|
–S. Andrew Josephson, MD
University of California, San Francisco
One important new finding is a green light to widen the current three-hour window for administering tissue plasminogen activator (tPA) to four-and-a-half hours. That is, said Dr. Josephson, “a very important advance that brings a number of people into the fold for acute lytic treatment.”
But he added that physicians should incorporate other new developments into their clinical practice as well. Those include performing a very aggressive work-up on patients with a transient ischemic attack (TIA) and following new guidance on the use of both antiplatelet and anticoagulant therapies and stents.
Expanding the use of tPA
All acute treatments for stroke are time-based, Dr. Josephson noted. (The onset of stroke, he reminded the audience, is the last time the patient was seen normal.) As of last fall, the timeline for one key treatment just got longer.
Findings from the ECASS 3 trial published in the Sept. 25, 2008, New England Journal of Medicine (NEJM) found that, at a median time of just under four hours, patients still had favorable outcomes with IV tPA. According to Dr. Josephson, the FDA will likely consider an application to increase the approved tPA-administration time to four-and-a-half hours.
Other tPA research has found that hospitalists do not need to work at large academic centers or have extensive experience with tPA to administer it safely, as long as they adhere to published guidelines and protocols.
A 6,500-patient study published in the Jan. 27, 2007, issue of The Lancet found tPA could be given safely in a large cohort of patients in the European Union, even at hospitals where physicians used the drug infrequently. “Some of these places had the opportunity to give this treatment very, very rarely,” he explained. “It was still very safe in that setting.”
The treatment timeline
Dr. Josephson said he also makes use of intraarterial tPA and mechanical embolectomy, treatments that are probably effective out to six and eight hours respectively. “Similar to the cardiac analogy, we can either lyse patients with IV tPA or take them to a neuro-interventional suite, do a four-vessel angiogram, see exactly where the clot is, advance a micro catheter, and either give tPA directly into that clot or remove the clot with an embolectomy device,” he pointed out.
Dr. Josephson emphasized that intraarterial tPA, although used widely, is not approved by the FDA because the initial studies of intraarterial lysis were performed by prourokinase. As of 2008 for embolectomy, however, two different devices are FDA-approved to open arteries in the brain.
As a hub-and-spoke model of stroke care continues to evolve in American hospitals—with some hospitals being certified as primary stroke centers—Dr. Josephson said he envisions a system of care where patients given IV tPA at a local stroke center would then be shipped to a facility like his own that can provide specialized care, such as intraarterial tPA or embolectomy.
Phasing out anticoagulants
Only 10 years ago, anticoagulants were standard therapy for most stroke patients. A growing body of evidence, however, has led to a drastic reduction in the use of blood thinners in most ischemic stroke cases.
Dr. Josephson said that multiple trials have found that “in almost every single scenario, antiplatelet drugs are just as good if not better.” Exceptions are patients with atrial fibrillation; stroke caused by some very specific cardioembolic sources; a vertebral or carotid artery dissection; or venous strokes.
New data last year in the September Archives of Neurology also showed that bridging patients with heparin, even for patients with atrial fibrillation (A-Fib), “has little effect,” Dr. Josephson said. “It increased the risk of hemorrhage and it didn’t help the patients at all.”
In those few patients he does treat with some bridging anticoagulation, “we never give a loading dose,” he explained. “Start them on an infusion, and be very careful not to make them supratherapeutic.”
Plavix v. Aggrenox: Flip a coin
It’s now your choice whether to give stroke patients Plavix or Aggrenox as antiplatelet therapy, according to the randomized PRoFESS study published in the Sept. 18, 2008, NEJM.
The 20,000-patient trial followed patients with both major and minor strokes for four years. It found that the two medications “are exactly the same” in terms of secondary prevention, Dr. Josephson said.
Each medication has pros and cons, he noted. Aggrenox has several complicating factors, including severe headaches in many patients; a slightly higher rate of hemorrhage compared with Plavix in the PRoFESS trial; and the fact that the drug can’t be crushed and placed in feeding tubes for dysphasic patients.
Plavix, however, isn’t popular with surgeons, who worry that it may cause excess bleeding during certain surgeries. That may make it the wrong choice for patients having surgical procedures—such as cardiac revascularization—following a stroke or TIA.
Guidelines still recommend against using the two medications together, Dr. Josephson noted, or in combination with aspirin. And when patients have a stroke while taking one of the two antiplatelets, should you switch them to the other? “We have absolutely no idea,” Dr. Josephson said, although that’s what he tends to do. “There’s no right answer. But the wrong answer is probably to switch them to anticoagulation, given the evidence for antiplatelets in secondary stroke prevention.”
Today, most stroke patients should be put on high-dose statin therapy, Dr. Josephson pointed out. He cited the SPARCL trial, published in the Aug. 10, 2006, NEJM, in which 80 mg of atorvastatin effectively prevented a second event in stroke and TIA patients with an LDL greater than 100 mg/dL over a five-year period.
Dr. Josephson added that it is still unclear whether lower doses or other types of statins would provide the same benefits. But based on the data, he puts “everybody who has a stroke or TIA whose LDL is greater than 100 on 80 mg of atorvastatin.”
He also pointed out that practitioners’ wild enthusiasm for stenting over endarterectomy may finally be coming to an end.
Stenting enjoyed a heyday after the SAPPHIRE trial was published in the Oct. 7, 2004, NEJM. That study found stenting to be just as effective as endarterectomy in very high-risk patients.
However, the SPACE trial published in the Oct. 7, 2006, issue of The Lancet indicated that stenting could not be proven to be non-inferior to endarterectomy. According to Dr. Josephson, a study also found stenting significantly increased the short-term risk of stroke and death. He now recommends endarterectomy to revascularize most of his stroke and TIA patients.
Dr. Josephson also pointed out that endarterectomies should be performed within two weeks to realize the maximum benefit of secondary stroke prevention. For some patients with a minor stroke or TIA, he added, he prefers to have the procedure done as early as the same day.
More monitoring for A-Fib patients
Another new development has to do with A-fib detection. Because the presence of A-fib changes physicians’ stroke management, anticoagulation patients are typically kept on cardiac telemetry for 48 hours.
However, Dr. Josephson pointed to soon-to-be-published results of research from his own institution. Patients found to be negative for A-fib with typical cardiac telemetry for 48 hours and no other cause of stroke were sent home with a continuous telemetry event monitor for 30 days.
Fully 20% of those patients actually were found to have A-fib. “We are missing a tremendous amount of A-Fib just by doing short-term monitoring,” said Dr. Josephson. Extended monitoring seems to make sense “in patients who you don’t have an otherwise easy explanation for why they had a stroke.”
Intensifying TIA workup
Another “big pendulum swing” in stroke care is the approach to patients with TIA. These patients, Dr. Josephson said, merit aggressive workup and should get the same treatment as if they’d had an actual stroke.
Previous guidelines had indicated that TIA patients should have a non-urgent, outpatient workup. But findings from the SOS TIA trial published in the November 2007 issue of Lancet Neurology and from the EXPRESS trial published in the Oct. 20, 2007, issue of The Lancet went much further. TIA patients in these studies received—as an urgent outpatient or in a 24-hour TIA center—a full workup, including echocardiogram, carotid evaluation, antiplatelets (or anticoagulants if indicated) and statins.
The results? Patients’ risk of stroke was reduced by 80% compared with predicted risk. “This really has changed the field,” pointed out Dr. Josephson, adding that TIA patients at UCSF are now admitted to the hospital and aggressively worked up. While some disability often ensues once a stroke occurs, “TIA is our version of unstable angina,” he said. “It is our opportunity to intervene and really make a difference.”
Sara Jackson is a freelance health care writer based near Richmond, Va.
One neurohospitalist’s imaging protocol
DATA STILL MAY BE SCARCE on the question of how imaging can help with stroke diagnosis. But clinical experience shows that there are technologies you can use to good effect, said S. Andrew Josephson, MD, a neurohospitalist and assistant professor of neurology at the University of California, San Francisco (UCSF).
At last year’s annual UCSF hospital medicine conference, Dr. Josephson shared the imaging menu he relies on to help diagnose and manage stroke. That protocol includes:
- Noncontrast CT. This gives an initial determination of whether the event is an ischemic or hemorrhagic stroke. “CT is essentially 100% sensitive for blood,” he explained. “That’s the only thing we’re looking for here.”
- CT angiography. This gives physicians a picture from the top of the heart to the top of the head, said Dr. Josephson, making it easier to spot some clots.
- CT perfusion study. The perfusion map is invaluable, Dr. Josephson pointed out, because it identifies tissue types by color: Green areas are ischemic but have not infarcted, while red areas are already dead. That map can tell exactly how much tissue is salvageable. “If I can revascularize a patient quickly,” he explained, “I can save everything in green.”
In the future, he said, he expects perfusion maps to guide actual stroke treatment. Patients with a majority of green (viable tissue) will receive aggressive clot-busting therapy, whereas patients with more red or non-viable tissue might not, in light of their higher hemorrhage risk.
- MRI. CT scans may not show ischemic stroke, but diffusion-weighted MRI scans are 100% sensitive for identifying an ischemic stroke up to seven days after the event. They are also easier for a non-radiologist to read, Dr. Josephson noted. “It doesn’t take a neuroradiologist to say, ‘Hey, that big bright white thing on these diffusion-weighted images is the stroke.’ ”
- TEE. Dr. Josephson said he now makes more extensive use of transesophageal echocardiograms (TEEs)—instead of transthoracic echocardiograms (TTEs)—based on results from a study published in the Oct. 1, 2006, issue of Stroke. Among patients studied whose stroke had a cardiac cause who received both TTE and TEE, 70% were apparent only on a TEE. (Most, he said, were left atrial thrombi.)
He and his colleagues began ordering a TEE for many stroke patients whose cause was unexplained. That’s especially true for patients younger than age 55, or those whose initial TTE is abnormal.
Permissive hypertension may protect tissue
WHAT’S THE SINGLE BIGGEST MISTAKE ED physicians and hospitalists make in stroke care? According to S. Andrew Josephson, MD, a neurohospitalist and assistant professor of neurology at the University of California, San Francisco (UCSF), it’s lowering patients’ blood pressure.
“We have good data and guidelines to suggest allowing permissive hypertension in somebody with an ischemic stroke to at least 200-220 systolic,” Dr. Josephson explained at last year’s UCSF hospital medicine conference.
The one exception is when you’re administering tPA. That’s because all the trials supporting tPA have been on patients whose blood pressure was kept below 185 systolic. Stroke patients’ blood pressure is high because the body is trying to get collateral flow to those areas of the brain not getting enough blood, he explained. That high blood pressure may actually be protecting tissue that otherwise would be starved for oxygen.