Platelet Function Testing Important With Pipeline Embolization

Nancy A. Melville

April 26, 2017

LOS ANGELES — Patients with intracranial aneurysm who respond poorly to the antiplatelet drug clopidogrel when treated with flow diversion using the Pipeline embolization device (Medtronic) have significantly higher rates of postprocedural thromboembolic complications if they are not switched to alternative antiplatelet regimens, underscoring the importance of platelet function testing before the procedures.

"These findings indicate that platelet function testing is warranted for all patients treated with the Pipeline embolization device," Christoph J. Griessenauer, MD, said in presenting the findings here at the 2017 American Association of Neurological Surgeons (AANS) 2017 Annual Scientific Meeting.

"Clopidogrel non-responders experience a high rate of thromboembolic complications when compared to clopidogrel responders unless alternative antiplatelet regimens are administered," said Dr Griessenauer, from the Division of Neurosurgery, Department of Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts.

The study was also published online April 14 in the journal Stroke.   

The Pipeline embolization device is notable for having a higher surface coverage than other intracranial stents, the authors note, and with increased membrane exposed to the bloodstream, dual-antiplatelet therapy is necessary to prevent thromboembolic complications.

However, the most commonly used dual therapy, aspirin and clopidogrel, has the important caveat that patients can have poor response to clopidogrel for wide-ranging reasons, including nonadherence, interactions with drugs such as statins or proton-pump inhibitors, or genetic factors, they point out.

Patients who can be identified through various platelet function testing methods as not adequately responding to clopidogrel may receive alternative treatments, such as being placed on the alternative ticagrelor or administered a clopidogrel boost.

The utility of platelet function testing is controversial, however, largely because of lackluster results with its use in coronary stenting.

To better evaluate the effects of testing in the neurointerventional setting, Dr Griessenauer and colleagues retrospectively reviewed data on 402 patients with 465 intracranial aneurysms treated in 414 Pipeline embolization procedures at three institutions from 2009 to 2016.

Patients, who were 82% female with an average age of 58 years, received three different methods of platelet function testing at the sites: light transmission aggregometry, whole blood aggregometry, or the point-of-care VerifyNow test (Accriva Diagnostics).

Patients shown to respond to clopidogrel were continued on the dual therapy of aspirin 325 mg and clopidogrel 75 mg for 3 to 14 days before surgery. Those found to be nonresponders were switched to the antiplatelet medication ticagrelor, maintained on clopidogrel, or administered a 600 mg clopidogrel boost.

The results showed thromboembolic complications in 5.6% of clopidogrel responders and 17.4% of nonresponders (P = .0002).

In the specific nonresponder subgroups, those switched to ticagrelor had complication rates of just 2.7%. Likewise, nonresponders who received a clopidogrel boost within 24 hours before the procedure also had substantially lower rates of thromboembolic complications when compared with nonresponders who did not get the boost (9.8% vs 51.9%; P = .00004).

Significant predictors of complications included nonresponse to clopidogrel vs response (odds ratio [OR], 0.23; P = .0001), nonresponders who switched to ticagrelor compared with not switching (OR, 0.08; P = .01), and nonresponders who did not receive a clopidogrel boost vs those who did (OR, 0.11; P = .0003).

Dr Griessenauer noted that no differences were seen in terms of the type of platelet function test and thromboembolic complications. In addition, there was no association of clopidogrel responder status and hemorrhagic complications.

With use of the Pipeline embolization device rapidly expanding to as many as 50,000 stents worldwide and 20,000 in the United States, the findings are highly important, said Adam S. Arthur, MD, MPH, commenting on the study at the meeting.

"It's clear antiplatelet therapy suddenly makes a big difference to our patients," said Dr Arthur, director of cerebrovascular and endovascular neurosurgery at the University of Tennessee Department of Neurosurgery, in Memphis.

"Any modifiable factors that could change the morbidity and mortality of this treatment for aneurysms could potentially significantly improve outcomes for a large number of patients."

"One of the major disadvantages for clopidogrel is that there appear to be a range of factors that can make it ineffective for our patients, and what's worse is the immunity seems to trace to things like hypercholesterolemia, which is linked to a higher risk of aneurysms," he said.

The findings underscore the potential benefits of platelet function testing and adjusting treatment according to the results, he added.

"This study suggests that there may be a significant benefit to changing your antiplatelet therapy from clopidogrel to ticagrelor in patients who are resistant, or, as some are already doing, even starting with ticagrelor rather than clopidogrel."

"We need more comparative data on the relative risk of various antiplatelet strategies for aneurysm patients being treated with flow diversion."

Dr Griessenauer has disclosed no relevant financial relationships. Study coauthors Adnan H. Siddiqui and Elad I. Levy have relationships with Covidien. Dr Arthur's disclosures include relationships with Medtronic, Stryker, Johnson & Johnson, Siemens Medical Systems, Cerebrotech, and Penumbra.

Stroke. Published online April 24, 2017. Abstract

American Association of Neurological Surgeons (AANS) 2017 Annual Meeting. Abstract 602. Presented April 24, 2017.

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