An innovative embolization device continues to show solid results in difficult-to-treat large intracranial aneurysms in real-world practice, according to a postmarket study published in the December 2012 issue of Neurosurgery. The findings also highlight lesion locations that should probably not be attempted with the device due to increased risk of serious and often fatal complications.

For the prospective registry, investigators led by Elad I. Levy, MD, of the University at Buffalo (Buffalo, NY), analyzed data on 62 procedures in which the Pipeline Embolization Device (PED; ev3/Covidien, Irvine, CA) was used to treat 58 aneurysms in 56 patients at 7 US centers. The aneurysms were considered to carry a high risk of recurrence with standard coil techniques or were judged otherwise unsuitable for such procedures.

The PED is an expandable braided mesh cylinder composed of platinum and a cobalt chromium alloy. Deployed across the neck of the aneurysm, it diverts blood flow away from the lesion and through the vessel, enabling a protective clot to form. Over time, endothelial tissue grows into the scaffold across the neck, sealing off the aneurysm from circulation.

The PED received US Food and Drug Administration approval for the treatment of large or giant wide-necked aneurysms in the internal carotid artery from the petrous to the superior hypophyseal segments in April 2011 based on results of the Pipeline for Uncoilable or Failed Aneurysms (PUFS) trial. The registry encompasses patients treated from May 6, 2011, through January 26, 2012.

Almost two-thirds of aneurysms (n = 37) were located in approved areas. However, 13 lesions (23%) were situated in the anterior circulation distal to the superior hypophyseal artery segment and 8 (14%) were in the vetebrobasilar system.  

Complete Procedural Success  

A total of 123 PEDs—an average of 2 per aneurysm—were deployed, all successfully. A quarter of the aneurysms required use of adjunctive detachable coils. Procedural events calling for rescue procedures were uncommon, and none had lasting effects.

The rate of major complications, defined as permanent disability or death resulting from perioperative or delayed complications, was 8.5%. Six perioperative thromboembolic events occurred, 5 of them in vertebrobasilar aneurysms. In addition, there were 4 postoperative hemorrhages (6.9%), all fatal. Two occurred in patients with ruptured giant basilar trunk aneurysms, one the first day after the procedure and one 2 months later. The other 2 hemorrhages, which occurred in ophthalmic aneurysms, had recently ruptured and been treated with coil embolization in a prior procedure.

Complete Occlusion Achieved in Two-Thirds of Aneurysms

Of 19 patients with follow-up angiography at 3 months, 13 (68%) achieved complete aneurysm occlusion, while 5 had a neck remnant only and 2 had residual filling of the aneurysm. Two patients presented with flow-limiting in-stent restenosis, 1 with symptoms at 2 months and 1 without symptoms at 3 months. Both patients underwent successful balloon angioplasty.

The authors conclude that “[l]ong-term data are needed to establish long-term efficacy and to understand the delayed complications of this new technology.”

In a telephone interview with TCTMD, Christopher J. Moran, MD, of Washington University School of Medicine (St. Louis, MO), said the reported two-thirds success rate in the study is “pretty typical” and will improve over time as more aneurysm occlusions develop and are confirmed in follow-up. Moreover, the fact that the few instances of device stenosis were successfully resolved by balloon angioplasty is “a useful bit of information,” he added.

As for the durability of the therapy, Dr. Moran noted that over 5,000 cases have been performed in Europe since 2007, and thus far among the fully occluded aneurysms there have been no reports of reopening.

Putting Complications in Context

Overall, however, the study focuses on quantifying and characterizing complications, Dr. Moran said. As the data show, aneurysms in the vertebrobasilar circulation can be very difficult to treat, he observed, especially fusiform lesions. The latter long arterial segments contain small perforating branches that supply critical areas of the brain, he explained. Like the authors, Dr. Moran suggested limiting the number of devices used in this area to reduce the chances of covering these vital perforator arteries.

Although the current findings may discourage clinicians from using the PED in fusiform aneurysms, more focal lesions in the vertebrobasilar territory will probably continue to be treated with the device, he predicted, especially since it represents a kind of last resort for patients with a very poor prognosis.

Hemorrhagic complications may be related to bits of debris that form on catheters or wires or are knocked loose during the procedure, causing small infarcts, Dr. Moran observed. These infarcts may then bleed in the presence of anticoagulation and antiplatelet therapy. Ischemic events may be due to the same source, he added, especially if patients are less responsive to antithrombotic agents.

Trend Toward Off-Label Use?

The overall proportion of aneurysms that are suitable for treatment with the PED remains to be seen, Dr. Moran said, although “for the on-label indications it’s going to be more than we expected.” Roughly 2,000 procedures have already been performed in the United States since approval in 2011, he noted, despite the need for operators to “get up to speed.” But perhaps more interesting, he added, is growing off-label use. In this study, 40% of procedures were performed in non-approved aneurysms, as are more than half in his own practice, he reported.

The study complication rate may be higher than the 5.6% incidence in the PUFS trial, he observed, but it is “much better than anything else we have to offer patients.” Going forward, however, improvement may stall, Dr. Moran suggested, because although operators are gaining experience, they are also treating more problematic cases. Also, the learning curve is fairly steep, he noted, and “the device can be a little quirky.”

For the most part, the neurosurgical community has welcomed the PED device “with open arms,” Dr. Moran commented. “It has changed the way we look at aneurysms, enabling us to treat ones we couldn’t do anything about before—or at least not as well or as safely.” And new iterations of the PED, as well as competition from other technologies, are on the way, he added.

Study Details

Overall, patients averaged 59 years of age and 84% were women. All were pretreated with a dual antiplatelet regimen: typically aspirin 325 mg daily and clopidogrel 75 mg daily for elective procedures and a 650 mg loading dose of aspirin and a 600 mg loading dose of clopidogrel for emergent procedures.

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