The clot-busting drug tissue plasminogen activator (tPA) revolutionized stroke care when it was approved almost a decade ago, offering greater hope of recovery following an acute ischemic stroke. Now, endovascular therapy (ET) techniques are ushering in a new standard of care that may have a similarly dramatic effect on patient outcomes.
Experts have known about the potential of ET for some time, but it has taken trial and error to figure out the best techniques. That effort, along with advances in technology, led to the long-awaited positive outcomes of the ESCAPE and other similar trials reported earlier this year at the International Stroke Conference in Nashville.
“We've finally found the right paradigm,” said ESCAPE's senior author Michael Hill, MD, professor of neurology at the University of Calgary and director of the Calgary Stroke Program for Alberta Health Services in Canada. “The ability to choose the right patients using imaging, to move fast, and to access advanced technology were all key to recent successes with ET.”
In ESCAPE and two other trials EXTEND-IA and MR CLEAN investigators used imaging to identify patients with large vessel blockages and salvageable brain tissue, both of which are required for ET. The trials also emphasized initiating treatment as quickly as possible and using advanced retrievable stent technology to remove clots.
ESCAPE and EXTEND-IA were stopped early for efficacy after it became clear that patients who underwent ET had significantly better outcomes than control groups. Two other trials have since reported similarly positive results SWIFT PRIME and REVASCAT (see sidebar).
As impressive as those findings are, it remains to be seen whether ET can become standard practice outside of major stroke centers. The institutions that participated in the studies all had access to sophisticated infrastructure, advanced technology, and experts in stroke care.
“Successful treatment requires 24-hour staffing with specialists and neuro-interventionists and the infrastructure to continuously evaluate these patients,” said Tudor Jovin, MD, associate professor of neurology and neurosurgery, director of the University of Pittsburgh Medical Center's (UPMC) Stroke Institute, and a principal investigator in the REVASCAT trial. “The model in the future may be to have centralized care, akin to trauma centers or catheterization labs.”
How it works
The first step in delivering successful ET is selecting patients who are most likely to benefit, which in the past may have been left to clinical judgment, said Dr. Hill. By using advanced imaging, researchers were able to identify patients with enough potentially salvageable brain tissue to benefit from reperfusion.
“There needs to be explicit recognition that sometimes it's too late for ET, and you're just exposing a patient to risk by treating them,” he said. “You need to identify patients with blocked arteries who do not already have well-established stroke.”
It's standard practice for stroke patients to undergo non-contrast computed tomography (CT) scans upon arrival at the hospital to determine if they have intracranial hemorrhage, said S. Andrew Josephson, MD, medical director of inpatient neurology and head of the neurohospitalist program at the University of California, San Francisco.
However, the new studies demonstrate that more precise imaging of the blood vessels, using CT angiography or magnetic resonance angiography, is necessary to select patients for ET.
Once a patient has been identified as eligible for ET, speed is of the essence. “It's quite clear from these trials that patients with the most severe type of stroke with large vessel occlusion should be taken for endovascular therapy within 6 hours of the last time they were seen well,” Dr. Josephson said.
In ESCAPE, Dr. Hill and his colleagues used CT angiography to confirm that patients had large vessel blockages, small infarct core, and moderate-to-good collateral circulation. Eligible patients were then rushed to the procedure room and underwent reperfusion less than 90 minutes from the time of their first CT scan.
At UPMC, Dr. Jovin and his team streamlined their workflow by performing some tasks simultaneously rather than sequentially. For example, the stroke neurology team was called in immediately upon identification of a patient with severe stroke so that procedures could be started as soon as confirmatory imaging results were available.
“We learned very convincingly that speed of reperfusion is critical,” said Dr. Jovin. “In the first generation of ET trials, it took 2 to 3 hours from the time a patient arrived at the hospital to initiation of the procedure, and another 90 minutes to open up the vessel. In ESCAPE and all other similar trials, aggressive efforts were in place to reduce those times to the minimum.”
Another key to the success of the trials was use of retrievable stent technology. A retrievable stent is attached to a catheter that is inserted through an incision in the groin and threaded up to the brain, where it props opens the clogged vessel and captures the clot. Both clot and stent are removed together.
“The newer stents open up the vessel to a larger extent and do it much faster compared to older devices,” said Dr. Jovin. As a result, “the time from hospital arrival to reperfusion was dramatically shorter in our study compared to past trials.”
Expanding access to care
ET holds the possibility of better outcomes, but only for patients transported to a major stroke center within several hours of experiencing symptoms. Currently, only a small percentage of patients who suffer an acute ischemic stroke are admitted to a hospital within the 4.5-hour treatment window for administering tPA.
Some stroke centers are trying to improve patients' odds of getting rapid treatment through the use of mobile stroke units (MSUs). Building on a concept that began in Germany, physicians at Memorial Hermann Hospital-Texas Medical Center (MMH-TMC) in Houston last year launched the first mobile stroke unit in the country and are collecting data on whether the service leads to better outcomes.
“It's not just about speeding patients to treatment but also identifying the best candidates for endovascular therapy,” said James Grotta, MD, director of stroke research in the Clinical Institute for Research and Innovation at MMH-TMC and director of the Mobile Stroke Unit Consortium in Houston. “We have the eyes of a neurologist on the patient in the pre-hospital environment so that eligible patients can go directly to the endovascular suite when they get to the hospital.”
MMH-TMC's mobile unit arrives on the scene along with local emergency medical services after every report of a stroke. After initial examination, patients who are within the 4.5-hour window of symptom onset are moved onto the MSU to be further evaluated and undergo a CT scan. Administration of tPA begins immediately in eligible patients as they are being transported to the nearest certified stroke center.
Currently, the Houston unit treats about 2 patients per week, with 40% treated within 60 minutes of symptom onset, when tPA is likely to be most effective, said Dr. Grotta. In contrast, patients transported by regular ambulance wait about 60 minutes to receive treatment after arriving in the emergency department, according to a 2014 study in the Journal of the American Medical Association. The study also found that shorter “door-to-needle” times were associated with lower in-hospital mortality, more frequent discharge to an independent environment, and lower rates of tPA complications.
However, cost may interfere with widespread adoption of MSUs. MMH-TMC spent about $400,000, excluding personnel and basic vehicle costs, to equip its unit with a CT scanner and point-of-care lab testing, as well as telemedicine capabilities, which eliminate the cost of having a vascular neurologist physically on board. On-unit staff includes a paramedic, CT technician, and registered nurse experienced in acute stroke management.
Dr. Grotta hopes to convince Medicare and other payers that investing in MSUs will pay off in long-term cost savings due to better patient outcomes. According to the CDC, caring for stroke patients now costs the nation about $34 billion annually in health care services, medications, and lost productivity.
“Considering the lifetime cost of caring for stroke patients, the one-time cost of a vehicle that will last for 10 to 20 years is pretty small in comparison,” said Peter Rasmussen, MD, director of the Cerebrovascular Center at Cleveland Clinic, which launched a mobile stroke service in the Cleveland metropolitan area earlier this year. And MSUs are no longer out of reach for many communities, he added, due to the availability of portable telemedicine units and more reliable Internet connections, which have driven costs down.
“Telemedicine makes these units possible from a cost-effective standpoint,” he said. Increasingly fast and reliable broadband has reduced the time and cost of transmitting CT scans and ensured reliable video connections with hospital-based neurologists.
MSUs not only get patients into treatment faster but also intelligently triage patients to appropriate care and alert hospital-based stroke teams in advance of arrival if a patient is eligible for ET, said Dr. Rasmussen.
“Because we have access to imaging and physician evaluation on the unit, we can take patients who do not have large vessel blockage to their community hospital and transport those that need a higher level of care directly to a neurosurgical center,” he said. “So far, we have had almost perfect triage where no patient has required a second transfer to another hospital due to medical need.”
That ability could be key to making the latest ET techniques available to a wider population, noted Dr. Josephson. A future model might involve MSUs integrated into networks of hospitals tied to a comprehensive stroke center where patients are taken immediately in the event of severe stroke.
“These recent trials are a game changer, but we're in a time analogous to earlier advances in cardiology, when not every hospital had an interventional cardiologist who could perform cardiac catheterization and angioplasty,” he said. “As those procedures became more common, more hospitals had the specialists, and I think that's what will happen with stroke.”