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Dose adjustment of clopidogrel in hyper-responder patients with unruptured intracranial aneurysms treated with stents
  1. Alejandro González1,2,
  2. Joaquin Ortega-Quintanilla1,2,
  3. Elena Zapata-Arriaza1,2,
  4. Asier de Albóniga-Chindurza1,2,
  5. Jose Raul García-Lozano3,
  6. María Isabel Luque Vega4,
  7. Aurelio Cayuela5
  1. 1 Department of Radiology, Interventional Neuroradiology, Virgen del Rocío University Hospital, Seville, Spain
  2. 2 Neurovascular Research Laboratory, Institute of Biomedicine of Seville-IBiS, Seville, Spain
  3. 3 Department of Immunology, Virgen del Rocío University Hospital, Seville, Spain
  4. 4 Department of Hospital Pharmacy, Virgen del Rocío University Hospital, Seville, Spain
  5. 5 Unit of Clinical Management of Public Health, Prevention and Promotion of Health, Area of Sanitary Management South of Seville, Seville, Spain
  1. Correspondence to Dr Alejandro González, Department of Radiology, Interventional Neuroradiology, Virgen del Rocío University Hospital, Seville 41013, Spain; ggjandro{at}


Background The management of clopidogrel in hyper-responders has not been well described. We report the treatment and dose adjustment individualization with clopidogrel oral solution (COS) in hyper-responder patients with an unruptured intracranial aneurysm treated with a stent.

Methods A prospective study (2015–2018) in patients receiving clopidogrel prior to endovascular treatment was performed. Platelet reactivity after clopidogrel therapy was evaluated with the VerifyNow PRU test. Initial values ≤80 PRU (P2Y12 reactivity units) were classified as a hyper-response according to prior evidence. Patients were treated with clopidogrel for 7–10 days before stent treatment. Seven days post-procedure the dose of COS was gradually reduced (30 mg–20 mg–10 mg–5 mg) every 5 days to 5 mg (1 mL)/day.

Results Twenty patients with 24 aneurysms were classified as having a hyper-response to clopidogrel. Mean age was 55.2 years (range 42–64) and 80% were women. Mean baseline PRU value and the percentage of platelet inhibition were 16.4±11.5 PRU and 92.05±7.5%, respectively. The mean time used to decrease the dose of clopidogrel to 5 mg/day was 27±4.3 days. Modified dosing strategies were shown to increase the final PRU values and to decrease the percentage of platelet inhibition (137.42±27.4 and 41.5±14.8%, respectively). Two of the 20 patients with dose adjustment of oral solution of clopidogrel (5 mg/day) in our cohort exhibited a delayed conversion to hypo-response. No patients suffered thromboembolic events related to the dose adjustment of clopidogrel with 5 mg/day during the follow-up.

Conclusion Reduction of the daily maintenance dose of clopidogrel in hyper-responder patients could provide a similar antiplatelet effect to the standard dose of clopidogrel, allowing a PRU value in the optimal range.

  • clopidogrel
  • intracranial Aneurysm
  • stent
  • verifyNow PRU Test

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  • Contributors AG participated in the development and design of the study and writing of the article. JOQ, EZA, and AAC participated in patient inclusion, manuscript writing and revision. JRGL participated in genetic studies. MILV and AC participated in manuscript revision. AC carried out the statistical analysis.

  • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

  • Competing interests None declared.

  • Patient consent for publication Not required.

  • Ethics approval The study protocol was approved by the local Ethics Committee. After full explanation of the study, written informed consent was obtained from all of the patients.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data availability statement All data relevant to the study are included in the article or uploaded as supplementary information.