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A Matter of Time
Multispecialty involvement may be part of the solution to provide endovascular stroke therapy faster.
It has been more than 2 years since groundbreaking research was published showing that endovascular thrombectomy improved outcomes in patients with acute ischemic stroke with a large-vessel occlusion. The standard of care, IV tissue plasminogen activator, was often not adequate in these patients when used alone.
Since then, patients with an emergency large-vessel occlusion (ELVO) have been treated routinely with the devices studied in the groundbreaking trials — including stent retrievers such as Solitaire 2 and Solitaire FR (Medtronic) and aspiration thrombectomy reperfusion catheters such as the Penumbra System Max (Penumbra), as well as further iterations of the technologies such as the Trevo ProVue Retrieval System (Stryker Neurovascular/Concentric Medical).
The challenge, however, has been how to deliver the therapy to appropriate patients as soon as possible after onset.
“About 10% of the population of ELVO patients in [the United States] actually receive this treatment. The other 90% don’t,” Blaise Baxter, MD, FRCPC, chief of radiology at Erlanger Health System in Chattanooga, Tennessee; chair of radiology at the University of Tennessee College of Medicine; and president-elect of the Society of NeuroInterventional Surgery, told Cardiology Today’s Intervention.
In most cases, the devices are used by neurointerventionalists, but many centers do not have any neurointerventionalists on staff. Efforts are underway to realign systems of care so that ELVO can be diagnosed soon after onset and the patient directed to an endovascular-capable center. However, some experts believe that because many rural areas have no endovascular-capable centers for hundreds of miles, a better solution would be to allow interventional cardiologists and physicians from other specialties capable of performing endovascular therapy to use these devices in community hospitals, so patients would have access to state-of-the-art care without having to travel too far.
© Lisa Clark
“The major issue in ischemic stroke intervention is total procedure time,” Cardiology Today’s Intervention Editorial Board member Mark H. Wholey, MD, emeritus chairman of the department of radiology and interventional radiology at University of Pittsburgh Medical Center – Shadyside, said in an interview. “No procedure I know of has the critical element of time being more demanding than stroke.”
Improvement in Outcomes
The benefit of endovascular thrombectomy in patients with ELVO was shown in trials such as MR CLEAN, ESCAPE, EXTEND-IA, REVASCAT and SWIFT PRIME. All showed that various endovascular thrombectomy technologies were associated with functional independence and neurological improvement at 90 days in the ELVO population.
“The technology advanced to the point where we were getting a high rate of recanalization in the arteries,” Mark Bain, MD, director of the cerebrovascular neurosurgery program and endovascular surgical neuroradiology program and staff neurosurgeon at Cleveland Clinic, told Cardiology Today’s Intervention. “Before, we were using devices that could maybe have a 30% to 50% chance of opening the artery. I think that clouded the data. In addition, our [patient] selection got better. There is no doubt that mechanical thrombectomy for large occlusions has taken off over the past 2 years. We are seeing more referrals to larger comprehensive stroke centers.”
As a result of MR CLEAN and other successful trials, Wholey said “there is a certain amount of enthusiasm for acute stroke management, more than in the past,” and the resulting activity has led to further improvement in time of stroke onset until hospital arrival, and subsequently, care at the time of in-hospital evaluation to the stroke intervention, recanalization and closure finalization.
Improvements have also come because of evolution in the technology, Bain said.
Since the publication of MR CLEAN and the other trials in early 2015, “there have been advances in some catheters we use where we’re able to navigate a 6F catheter into a middle cerebral artery, and many operators are now doing direct aspiration,” he said. “Some people are doing combination approaches using stent retrievers and aspiration. The newest development is balloon guide catheters being used in the carotid artery to prevent distal emboli. We’re getting much higher recanalization rates, lower rates of distal emboli in the arteries and improved patient outcomes.”
What may further promote use of the technology are cost analyses. In December 2016, an economic analysis of the SWIFT PRIME trial of the Solitaire stent retriever in patients with ELVO concluded that while index hospital costs were higher for patients treated with tissue plasminogen activator (tPA) plus the stent retriever vs. those treated with tPA alone, lifetime projections showed that compared with tPA alone, tPA plus the stent retriever was associated with gains in quality-adjusted life-years and cost savings of $23,203 per patient (see Figure).
“Patient outcome is our focus, but we want to deliver [that] in the most cost-effective way possible,” Baxter said. “Having a patient walk out of the hospital neurologically intact 3 or 4 days after treatment [will cost much less long term] vs. the patient being permanently disabled from that day forward. A severely disabling stroke for [a young] patient that takes them out of the workplace and a functional lifestyle has a huge cost impact for society.”
However, Christopher J. White, MD, MSCAI, FACC, FAHA, FESC, FACP, said faster time to recanalization is strongly linked to better outcomes, and there is much room for improvement in that area. White, a member of the Cardiology Today’s Intervention Editorial Board, is chief of medical services; medical director for system service lines and system chairman for cardiology at Ochsner Medical Center, New Orleans; and professor and chairman of medicine at the University of Queensland–Ochsner Clinical School.
“If the measure of success for stroke treatment is similar to the measure of success for MI, which would be door-to-balloon time, there has been no improvement in those metrics,” he said.
Realigning Systems of Care
Many ideas have been proposed to better maximize the number of patients with ELVO who can quickly obtain access to the endovascular technologies that improve chances for complete recanalization and better functional outcomes.
Through its Get Ahead of Stroke campaign, the Society of NeuroInterventional Surgery has been focused on streamlining the system of care to emphasize faster diagnosis of ELVO and prioritizing getting patients quickly to neuroendovascular-ready stroke centers.
“One of the downsides of stroke is that we don’t have the equivalent of ECG or troponin [for MI] to recognize someone is suffering this kind of stroke,” Baxter said. “The next thing is to recognize this subset of stroke patients is on an emergency treatment timeline. We are looking at better ways and tools. Some areas have mobile stroke units which bring CT and other imaging capability to the ambulance and getting a snapshot to see if there is an ELVO, which dictates EMS to take the patient to an neuroendovascular-ready center.”
Bain said the Cleveland Clinic mobile stroke units have worked well in practice and a benefit has been that “it forces the community, the ambulance drivers and the comprehensive stroke centers to get organized, just like we’ve done with trauma and acute MI. It’s all about access to care and coordinating the system, and once it’s coordinated, you’re getting the best patient outcomes.”
The Role of Cardiologists
Realigning systems to divert patients to comprehensive stroke centers faster may work in urban areas, but in areas without a nearby comprehensive stroke center and/or an institution with a neurointerventionalist on staff, it may be more feasible to have interventional cardiologists or other specialists perform the endovascular procedure and work with a neurologist to manage the patient, according to White and Wholey.
“There is a need for cardiologists as well as vascular radiologists to be trained for stroke intervention to alleviate the significant shortage of neurointerventionalists,” Wholey said. “Once they are trained, they will fill the serious gap that exists within the community hospital. They may not be needed at a comprehensive stroke center, which has an appropriate staff.”
If community hospitals have no one who can perform the endovascular procedure, the time to recanalization “isn’t going to [be improved] because the solutions proposed by those who would restrict the ability to treat patients would require a complex transport scheme that is very unlikely to work,” White said. “At least I’ve never seen it work in American medicine. Whereas the strategy with STEMI was to put [interventional cardiologists] in the community to provide patient care, the strategy for neuroradiologists appears to be to staff centers in population centers on both coasts and in major cities, but to leave an enormous number of patients without care in this country. Many of us argue that we could provide this care if we are allowed to expand the number of providers that could provide the care.”
Baxter said the best outcomes are “accomplished by providers having the appropriate training. It’s really a training issue. There’s no shortcut on the fellowship training. To use myself as an example, because I’m a neurointerventionalist, I can navigate blood vessels in the brain, but that doesn’t mean I could tackle complex cardiology cases. I would have to train for it, and get that training through a fellowship.”
White said, however, “the technical ability to open these arteries doesn’t require any neurological training. It’s endovascular treatment, de-clotting an artery. If I can treat 2,000 MIs, then it doesn’t take much for me to learn how to treat a stroke. [Neurointerventionalists] make it seem a lot more complicated than it actually is, particularly for people who are already certified to do carotid stenting, who already have the ability to safely place catheters in the neck.”
At Ochsner, White said there are now enough neurointerventionalists to cover all patients with ELVO, but the institution used to have only one on staff, and endovascular treatments for ELVO were shared by the neurointerventionalist and teams of interventional cardiologists working with neurologists. In 2015, White and his colleagues published an article in Catheterization and Cardiovascular Interventions showing that, among patients with acute ischemic stroke treated with catheter-based therapy at Ochsner, the 58 treated by an interventional cardiologist did not significantly differ from the 66 treated by a neurointerventionalist in metrics including 90-day modified Rankin Scale score, complication rate, or 30-day mortality (see Table).
While “I think anybody that has had sufficient neurointerventional training can do a procedure to take out a clot, it’s the preoperative selection and postoperative care that really enhances the patient outcomes,” Bain said. “Certainly, we want these procedures done, but we want them done in the right way. The answer is not to train more people or to have more fields involved. The answer involves reorganizing the stroke networks, the stroke transfer system and the primary stroke centers so that the correct patients goes to the correct center with trained neurointerventionalists who have completed a proper neurointerventional fellowship.”
Where that is not possible, White said, “in the absence of a [neurointerventionalist], a trained carotid stent operator with neurology guidance is a very effective provider. If I was trying to design a treatment algorithm for stroke, I would have ... everybody be treated within 90 minutes, just like we do with [acute MI]. If you want to transport a patient and can treat them within 90 minutes, be my guest. But that is a bar we couldn’t meet with MI, and I don’t think it’s a bar we can meet with stroke either.”
Wholey said the opportunity for interventional cardiologists to become involved in endovascular procedures for ELVO has not occurred on a widespread basis because “there has been some reluctance by industry to financially support this, which could be related to deep-seeded economics as well as turf issues.”
Steps for the Future
More research is underway that will help clinicians better determine the optimal ways to use endovascular technologies to treat patients with ELVO. Some findings, if positive, may help with cases where the time factor is an issue.
MR CLEAN and the other groundbreaking trials evaluated the efficacy of the devices when used within 6 hours of symptom onset. Now, trials are ongoing to determine if they are effective more than 6 hours after onset, Baxter said. “One trial just in the process of closing will help us with that population as well as patients where we can’t establish time of onset, such as in those with `wake-up strokes.’”
Another avenue of research, he said, is administering a neuroprotectant in the ambulance that may be able to stop the progress of cell necrosis, reducing the amount of damage that occurs before arrival to a hospital. “The investigators behind the ESCAPE trial have unveiled a new trial which is essentially ESCAPE plus a neuroprotection agent,” Baxter said.
More work needs to be done to use telemedicine to “get a patient seen by a neurologist as quickly as possible and getting those patients to care,” Bain said.
While there is disagreement about the best way to provide care quickly, no one disputes that any feasible solution involves providing treatment quickly or providing ways to mitigate cell necrosis that will occur rapidly if not countered.
“Procedure time is the answer to this whole situation,” Wholey said. “Unfortunately, transport from the community hospitals to stroke centers can result in unnecessary delays. To correct this situastion, we must not rely solely on stroke centers, but must include community hospitals with adiquitely trained staff. A similar situation with MI as been corrected by utililizing the peripheral hospitals and not exclusively the major centers.” — by Erik Swain
- References:
- Berkhemer OA, et al. N Engl J Med. 2015;doi:10.1056/NEJMoa1411587.
- Campbell BCV, et al. N Engl J Med. 2015;doi:10.1056/NEJMoa1414792.
- Goyal M, et al. N Engl J Med. 2015;doi:10.1056/NEJMoa1414905.
- Htyte N, et al. Catheter Cardiovasc Interv. 2015;doi:10.1002.ccd.25755.
- Jovin TG, et al. N Engl J Med. 2015;doi:10.1056/NEJMoa1503780.
- Saver JA, et al. N Engl J Med. 2015;doi:10.1056/NEJMoa1415061.
- Shireman TI, et al. Stroke. 2016;doi:10.1161/STROKEAHA.116.014735.
- For more information:
- Mark Bain, MD, can be reached at Cleveland Clinic, 9500 Euclid Ave., Cleveland, OH, 44195; email: bainm@ccf.org.
- Blaise Baxter, MD, FRCPC, can be reached at 975 E. Third St., Box 376, Chattanooga, TN 37403; email: blaise@tiiarad.com.
- Christopher J. White, MD, MSCAI, FACC, FAHA, FESC, FACP, can be reached at Ochsner Medical Center, 1514 Jefferson Highway, New Orleans, LA 70121; email: cwhite@ochsner.org.
- Mark H. Wholey, MD, can be reached at 320 E. North Ave. CVI I – NW Wing, Pittsburgh, PA 15212; email: markwholey@aol.com.
Disclosure: Bain reports consulting for Stryker Neurovascular. Baxter reports consulting and speaking for Medtronic, Penumbra and Stryker Neurovascular. White reports serving on the interventional management committee for the CREST-2 trial sponsored by the NIH. Wholey reports no relevant financial disclosures.