Endovascular Interventions for Acute Stroke: Promise or Peril?

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Endovascular interventions for acute ischemic stroke appear promising, but 2 new articles in Stroke and the Annals of Internal Medicine urge caution and the need for more research before a strong clinical opinion can be formed regarding the safety and efficacy of intravenous arterial therapies or neurothrombectomy devices.

In the first paper, Killian O’Rourke, MD, of the Dublin Neurological Institute (Dublin, Ireland), and colleagues conducted a systematic review of randomized controlled trials comparing percutaneous vascular interventions plus medical treatment with nonthrombolytic medical treatment alone for acute ischemic stroke. The review covered 4 trials (PROACT 1, 1998; PROACT 2, 1999; AUST, 2005; and MELT, 2007) involving 350 patients. All trials tested intra-arterial thrombolytic drugs (either urokinase or recombinant prourokinase) and 1 trial used guidewire-mediated clot disruption in some patients randomized to the intervention group.

Compared with medical therapy, the interventional treatment administered up to 6 hours after ischemic stroke significantly increased the proportion of patients with favorable outcome (modified Rankin score 0 to 2) at 3 months (RR 1.47, 95% CI 1.07-2.02).

Intervention was strongly associated with partial or complete angiographic recanalization to TIMI Grade 2 and 3 flow at 120 minutes (RR 4.02; 95% CI 2.32-6.95). Good neurological outcome (National Institutes of Health Stroke Scale 0 to 1) also was improved at 3 months in the intervention group (RR 2.03; 95% CI 1.21-3.40). There was no significant heterogeneity among the trials.

However, patients who received interventional treatment also were more likely to have symptomatic intracranial hemorrhage within 24 hours (RR 3.85; 95% CI 0.91-16.36).

“Overall, intervention results in a significant increase in the proportion of patients with a favorable outcome despite a significant increase in intracranial hemorrhage,” Dr. O’Rourke and colleagues write. “Further trials are needed to confirm or refute these findings and, given the cost and practical difficulties, to establish whether percutaneous techniques are feasible and cost-effective in wider clinical practice.”

Neurothrombectomy Devices Offer New Options

The second paper looked at neurothrombectomy devices for the treatment of acute ischemic stroke. Currently, 2 such devices, the Merci Retriever (Concentric Medical, Mountain View, CA) and the Penumbra System (Penumbra, Alameda, CA), have been approved by the US Food and Drug Administration. Both are endovascular devices that offer an alternative or complement to intravenous therapy by allowing the physician to manually remove a clot.

In their review, Craig I. Coleman, PharmD, and colleagues, of the University of Connecticut/Hartford Hospital Evidence-based Practice Center (Hartford, CT), reviewed 87 published articles, half of which included either the Merci (40%) or the Penumbra (9%) devices. The rest included several off-label devices. Overall, at 3 months, rates of successful recanalization varied widely with each device, as did rates of mortality and clinical effectiveness (defined as a modified Rankin score of 0 to 2; table 1).

Table 1. Three-Month Outcomes for Neurothrombectomy Devices

Successful recanalization was the only variable predictive of good outcomes, although concomitant use of intra-arterial thrombolytics was predictive of achieving recanalization. Variables that predicted worse outcomes included older age, higher baseline systolic blood pressure, higher baseline NIHSS scores, history of stroke, longer procedure duration, and documented occlusions of the internal cerebral artery.

Incidence of intracranial hemorrhage, both symptomatic and asymptomatic, and vessel perforation or dissection were the most commonly reported complications (table 2).

Table 2. Complications

Dr. Coleman and colleagues conclude that while neurothrombectomy devices offer “intriguing” options for treating patients with acute ischemic stroke, data are limited.

“Further research is needed on the topic, including randomized, controlled trials to determine the optimal device to use and the patient populations that are most likely to benefit from its use,” they write. “In addition, future studies should investigate whether neurothrombectomy devices affect final health outcomes associated with stroke rather than improving recanalization alone when compared with contemporary controls.”

Long Road Ahead

One ongoing study, IMS III (Interventional Management of Stroke III), is seeking to determine if a combined intravenous and intra-arterial therapy approach is superior to standard intravenous r-tPA alone when initiated within 3 hours of acute ischemic stroke onset. Both the Merci and Penumbra devices are part of the trial.

But IMS III, which began in 2006, has been slow to enroll patients, mainly because of the high early mortality rate, said Philip M. Meyers, MD, of Columbia University Medical Center (New York, NY), in a telephone interview with TCTMD.

“The reality is that even at a busy center like Columbia, we are only treating maybe 20 or 30 strokes a year,” he said. “The reason is that not many people show up in time to be treated. These interventions are exciting and potentially offer a lot if you can figure out how to get patients there in time and also who is most likely to benefit. Some people will have better ‘backdoor’ detour pathways to get blood flow around the areas that have irrevocably stroked, but we don’t have good methods for knowing who we should try [to intervene in] and who we shouldn’t.”

Another major issue is the difficulty of selecting patients for an intervention that not only may not work but may cause serious harm, such as perforation or bleeding.

In addition, Dr. Meyers said some clinicians may be so ingrained to use a specific protocol that they are resistant to enrolling patients in an interventional trial.

“The neurothrombectomy devices are exciting and potentially offer a lot, but we need more data from the ongoing trials, such as IMS III, to really move forward,” Dr. Meyers said. “I think we will see a lot more [endovascular therapies] for stroke, but the question is: Will we recognize when what [such therapies are] actually benefiting people and when they are not?”

 

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Sources:
1. Baker WL, Colby JA, Tongbram V, et al. Neurothrombectomy devices for the treatment of acute ischemic stroke: State of the evidence. Ann Intern Med. 2011;Epub ahead of print.

2. O’Rourke K, Berge E, Walsh C, Kelly PJ. Percutaneous vascular interventions for acute ischemic stroke. Stroke. 2011;Epub ahead of print.

 

• Dr. Meyers reports being an investigator for the IMS III trial.

 

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