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

Elias Atallah Department of Neurological Surgery, Thomas Jefferson University and Jefferson Hospital for Neuroscience, Philadelphia, Pennsylvania

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Hassan Saad Department of Neurological Surgery, Thomas Jefferson University and Jefferson Hospital for Neuroscience, Philadelphia, Pennsylvania

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Kimon Bekelis Department of Neurological Surgery, Thomas Jefferson University and Jefferson Hospital for Neuroscience, Philadelphia, Pennsylvania

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Nohra Chalouhi Department of Neurological Surgery, Thomas Jefferson University and Jefferson Hospital for Neuroscience, Philadelphia, Pennsylvania

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Stavropoula Tjoumakaris Department of Neurological Surgery, Thomas Jefferson University and Jefferson Hospital for Neuroscience, Philadelphia, Pennsylvania

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David Hasan Department of Neurological Surgery, Thomas Jefferson University and Jefferson Hospital for Neuroscience, Philadelphia, Pennsylvania

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Jorge Eller Department of Neurological Surgery, Thomas Jefferson University and Jefferson Hospital for Neuroscience, Philadelphia, Pennsylvania

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David Stidd Department of Neurological Surgery, Thomas Jefferson University and Jefferson Hospital for Neuroscience, Philadelphia, Pennsylvania

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Robert H. Rosenwasser Department of Neurological Surgery, Thomas Jefferson University and Jefferson Hospital for Neuroscience, Philadelphia, Pennsylvania

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Pascal Jabbour Department of Neurological Surgery, Thomas Jefferson University and Jefferson Hospital for Neuroscience, Philadelphia, Pennsylvania

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OBJECTIVE

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.

METHODS

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.

RESULTS

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.

CONCLUSIONS

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.
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