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

View More View Less
  • Department of Neurological Surgery, Thomas Jefferson University and Jefferson Hospital for Neuroscience, Philadelphia, Pennsylvania
Restricted access

Purchase Now

USD  $45.00

JNS + Pediatrics - 1 year subscription bundle (Individuals Only)

USD  $505.00

JNS + Pediatrics + Spine - 1 year subscription bundle (Individuals Only)

USD  $600.00
Print or Print + Online

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.

JNS + Pediatrics - 1 year subscription bundle (Individuals Only)

USD  $505.00

JNS + Pediatrics + Spine - 1 year subscription bundle (Individuals Only)

USD  $600.00

Contributor Notes

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

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

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

  • 1

    Akbari SH, Reynolds MR, Kadkhodayan Y, Cross DT III, Moran CJ: Hemorrhagic complications after prasugrel (Effient) therapy for vascular neurointerventional procedures. J Neurointerv Surg 5:337343, 2013

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 2

    Delgado Almandoz JE, Kadkhodayan Y, Crandall BM, Scholz JM, Fease JL, Tubman DE: Variability in initial response to standard clopidogrel therapy, delayed conversion to clopidogrel hyper-response, and associated thromboembolic and hemorrhagic complications in patients undergoing endovascular treatment of unruptured cerebral aneurysms. J Neurointerv Surg 6:767773, 2014

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 3

    Dobesh PP, Varnado S, Doyle M: Antiplatelet agents in cardiology: a report on aspirin, clopidogrel, prasugrel, and ticagrelor. Curr Pharm Des 22:19181932, 2016

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 4

    Guédon A, Clarençon F, Di Maria F, Rosso C, Biondi A, Gabrieli J, : Very late ischemic complications in flow-diverter stents: a retrospective analysis of a single-center series. J Neurosurg 125:929935, 2016

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 5

    Gupta R, Moore JM, Griessenauer CJ, Adeeb N, Patel AS, Youn R, : Assessment of dual-antiplatelet regimen for Pipeline Embolization Device placement: a survey of major academic neurovascular centers in the United States. World Neurosurg 96:285292, 2016

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 6

    Hanel RA, Taussky P, Dixon T, Miller DA, Sapin M, Nordeen JD, : Safety and efficacy of ticagrelor for neuroendovascular procedures. A single center initial experience. J Neurointerv Surg 6:320322, 2014

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 7

    Jones GM, Twilla JD, Hoit DA, Arthur AS: Prevention of stent thrombosis with reduced dose of prasugrel in two patients undergoing treatment of cerebral aneurysms with pipeline embolisation devices. J Neurointerv Surg 5:e38, 2013

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 8

    Leslie-Mazwi TM, Chandra RV, Oh DC, Nogueira RG: Novel use of prasugrel for intracranial stent thrombosis. J Neurointerv Surg 3:358360, 2011

  • 9

    Mega JL, Close SL, Wiviott SD, Shen L, Hockett RD, Brandt JT, : Cytochrome P450 genetic polymorphisms and the response to prasugrel: relationship to pharmacokinetic, pharmacodynamic, and clinical outcomes. Circulation 119:25532560, 2009

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 10

    Molyneux A, Kerr R, Stratton I, Sandercock P, Clarke M, Shrimpton J, : International Subarachnoid Aneurysm Trial (ISAT) of neurosurgical clipping versus endovascular coiling in 2143 patients with ruptured intracranial aneurysms: a randomised trial. Lancet 360:12671274, 2002

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 11

    Patti G, Ricottini E, De Luca L, Cavallari I: Safety and efficacy of switching from clopidogrel to prasugrel in patients undergoing percutaneous coronary intervention: a study-level meta-analysis from 15 studies. J Cardiovasc Pharmacol 67:336343, 2016

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 12

    Pistocchi S, Blanc R, Bartolini B, Piotin M: Flow diverters at and beyond the level of the circle of Willis for the treatment of intracranial aneurysms. Stroke 43:10321038, 2012

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 13

    Qureshi AI, Luft AR, Sharma M, Guterman LR, Hopkins LN: Prevention and treatment of thromboembolic and ischemic complications associated with endovascular procedures: Part I—Pathophysiological and pharmacological features. Neurosurgery 46:13441359, 2000

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 14

    Qureshi AI, Luft AR, Sharma M, Guterman LR, Hopkins LN: Prevention and treatment of thromboembolic and ischemic complications associated with endovascular procedures: Part II—Clinical aspects and recommendations. Neurosurgery 46:13601376, 2000

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 15

    Stetler WR, Chaudhary N, Thompson BG, Gemmete JJ, Maher CO, Pandey AS: Prasugrel is effective and safe for neurointerventional procedures. J Neurointerv Surg 5:332336, 2013

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 16

    Tan LA, Keigher KM, Munich SA, Moftakhar R, Lopes DK: Thromboembolic complications with Pipeline Embolization Device placement: impact of procedure time, number of stents and pre-procedure P2Y12 reaction unit (PRU) value. J Neurointerv Surg 7:217221, 2015

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 17

    Weerakkody GJ, Jakubowski JA, Brandt JT, Farid NA, Payne CD, Zhu J, : Comparison of speed of onset of platelet inhibition after loading doses of clopidogrel versus prasugrel in healthy volunteers and correlation with responder status. Am J Cardiol 100:331336, 2007

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 18

    Wiviott SD, Braunwald E, McCabe CH, Montalescot G, Ruzyllo W, Gottlieb S, : Prasugrel versus clopidogrel in patients with acute coronary syndromes. N Engl J Med 357:20012015, 2007

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation

Metrics

All Time Past Year Past 30 Days
Abstract Views 768 173 0
Full Text Views 882 330 37
PDF Downloads 506 165 17
EPUB Downloads 0 0 0