The use of alternatives to clopidogrel in flow-diversion treatment with the Pipeline embolization device

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Thromboembolic complications continue to be encountered with Pipeline embolization devices (PEDs) despite routine clopidogrel/aspirin antiplatelet therapy. This study examined the safety and efficacy of prasugrel in the management of clopidogrel-resistant patients treated for cerebral aneurysms.


Four hundred thirty-seven consecutive patients were identified between January 2011 and May 2016. Patients allergic, or having less than 30% platelet inhibition, to a daily 75-mg dose of clopidogrel received 10 mg of prasugrel daily (n = 20) or 90 mg of ticagrelor twice daily (n = 2). The mean (± SD) follow-up duration was 15.8 ± 12.4 months. The primary outcome was the modified Rankin Scale (mRS) score registered before discharge and at each follow-up visit. To control confounding, multivariable mixed-effects logistic regression and propensity score conditioning were used.


Twenty-six (5.9%) of 437 patients presented with a subarachnoid hemorrhage (SAH). The mean patient age was 56.3 years, and 62 were women (14.2%). One of the 7 patients lost to follow-up received prasugrel. One patient was allergic to clopidogrel and prasugrel simultaneously. All patients receiving prasugrel or ticagrelor (n = 22) had an mRS score ≤ 2 on their latest follow-up visit (mean score 0.67 ± 1.15). In a multivariate analysis, clopidogrel did not affect the mRS score on last follow-up (p = 0.14). Multivariable logistic regression showed that clopidogrel was not associated with an increased long-term recurrence rate (OR 0.17, 95% CI 0.01–2.70, p = 0.21), an increased thromboembolic complication rate (OR 0.46, 95% CI 0.12–1.67, p = 0.24), or an increased hemorrhagic event rate (OR 0.39, 95% CI 0.91–1.64, p = 0.20). None of the patients receiving prasugrel or ticagrelor died or suffered a long-term recurrence or a hemorrhagic event; only 1 patient suffered from mild aphasia subsequent to a thromboembolic event. Three patients taking clopidogrel died during the study: 2 from acute SAH and 1 from intraparenchymal hemorrhage. Clopidogrel was not associated with an increased mortality rate (OR 2.18, 95% CI 0.11–43.27, p = 0.61). The same associations were present in propensity score–adjusted models.


In a cohort of patients treated with PEDs, prasugrel (10 mg/day) was a safe alternative to clopidogrel-resistant or clopidogrel-allergic patients, or nonresponders.

ABBREVIATIONS DAPT = dual antiplatelet therapy; DSA = digital subtraction angiography; mRS = modified Rankin Scale; PED = Pipeline embolization device; SAH = subarachnoid hemorrhage; TRITON-TIMI 38 = Trial to Assess Improvement in Therapeutic Outcomes by Optimizing Platelet Inhibition with Prasugrel–Thrombolysis In Myocardial Infarction 38.

Article Information

Correspondence Pascal Jabbour, Department of Neurological Surgery, Thomas Jefferson University Hospital, 901 Walnut St., 3rd Fl., Philadelphia, PA 19107. email:

INCLUDE WHEN CITING Published online December 8, 2017; DOI: 10.3171/2017.5.JNS162663.

Disclosures Drs. Tjoumakaris and Jabbour report being consultants for Medtronic.

© AANS, except where prohibited by US copyright law.



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    Graph showing the mean values of the clinical outcomes according to the prescribed antiplatelet drug. pop. = population. Figure is available in color online only.


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