Low-Dose Prasugrel in Patients with Resistance to Clopidogrel for the Treatment of Cerebral Aneurysms (original) (raw)
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Interventional Neuroradiology, 2016
Background Thromboembolic complications are the main problem in stent-assisted coil embolization of unruptured intracranial aneurysms. The combination of aspirin and clopidogrel is generally used to decrease these complications, but some patients do not respond to clopidogrel and have a higher risk of stent thrombosis. In cardiology, clinical trials have shown that prasugrel reduced the incidence of ischaemic events in patients with acute coronary syndrome compared with clopidogrel but, according to several authors, prasugrel would produce an increased risk of cerebral haemorrhagic complications. Objective The purpose of this study was to determine whether prasugrel would be more effective than clopidogrel in reducing procedural events in patients with an unruptured aneurysm treated endovascularly with coils and stent. Materials and methods Two hundred consecutive patients with intracranial aneurysms were treated using coiling and stenting procedures. The first 100 patients were adm...
Journal of Neurosurgery, 2012
Object The optimal antiplatelet medication protocol for prevention of thrombotic complications after stent-assisted coil embolization of cerebral aneurysms is unclear. Early cessation of antiplatelet agents may be associated with an increased risk of cerebral ischemic events. In this study, the authors assess the incidence of stroke or transient ischemic attack (TIA) following discontinuation of a 6-week course of clopidogrel in patients with cerebral aneurysms treated with stent-assisted techniques. Methods A retrospective review was conducted in all patients with cerebral aneurysms undergoing stent-assisted coil embolization or stent-in-stent flow diversion at the University of Iowa during a 24-month period. The antiplatelet protocol was 81 mg aspirin and 75 mg clopidogrel daily for 6 weeks, followed by 325 mg aspirin daily indefinitely. The incidence of stroke or TIA was determined by a retrospective review of medical records generated during a 3-month period following discontinu...
American Journal of Neuroradiology, 2012
BACKGROUND AND PURPOSE: Antiplatelet drug resistance has been associated with thromboembolic complications in patients after coronary stent placement. It has not been well-studied in patients who have neurovascular stent-placement procedures. This study aimed to analyze the relationship between antiplatelet drug resistance and neurovascular stent-placement complications. MATERIALS AND METHODS: A prospective data base of all patients treated at our institution was used to identify patients with neurovascular stent-placement procedures. During a 4.5-year period, all patients undergoing neurovascular stent placement were evaluated for aspirin and clopidogrel resistance by using the VerifyNow assay. During an observational phase, all patients received 75 mg of clopidogrel and aspirin (group A). During the intervention phase (group B), patients were given additional clopidogrel on the basis of the clopidogrel resistance assay. We assessed the development of thromboembolic complications within 30 days of the procedure in patients who were resistant-versus-nonresistant to clopidogrel. RESULTS: Of 96 patients who had neurovascular stent placement, 5.2% were resistant to aspirin and 36.5% were resistant to clopidogrel. Periprocedural thromboembolic complications were seen in 7 patients (7.3%). In a multivariate logistic regression model, clopidogrel resistance, higher diastolic blood pressure, and lack of statin use were significantly associated with periprocedural thromboembolic complication. There was a nonsignificant decrease in thromboembolic complications in patients whose clopidogrel dosage was tailored to the assay. CONCLUSIONS: In our series, clopidogrel resistance was associated with increased periprocedural thromboembolic complications from neurovascular stent-placement procedures. Targeting the clopidogrel dose to platelet inhibition assays may improve clinical outcomes and requires further study. ABBREVIATIONS: ACT ϭ activated clotting time; ARU ϭ aspirin reaction units; LTA ϭ light transmittance aggregometry; PCI ϭ percutaneous cardiovascular interventions; PRU ϭ P2Y12 reaction units
Neuroradiology, 2020
Purpose In patients requiring stent procedures, resistance or hyperresponsiveness to antiplatelet medications is often observed. This study aims to evaluate the efficacy and safety of tailoring medications in these patients. Methods This retrospective study included 223 patients who underwent endovascular treatment for intracranial aneurysm between October 2018 and October 2019. Patients were categorized as hyporesponsive, hyperresponsive, and normoresponsive groups according to the initial PRU response. For the hypo-or hyperresponders, we tailored medication by modifying the dose or changing the drug. PRUs before and after tailoring were compared in each group. PRU reponses in patients who underwent Cytochrome P450 2C19 (CYP2C19) genotyping were also determined. Results Of the 73 clopidogrel-resistant patients, the mean PRU values after tailoring showed a greater decrease in the group that switched to prasugrel (n = 56), from 223 to 131, than in the clopidogrel reloading group (n = 17), from 238 to 209. In 31 hyperresponders, PRU increased from 49 to 94 after the dose adjustment. CYP2C19 genotyping showed that PRU tended to increase as the number of mutated alleles increased. There were five (2.3%) ischemic events (three transient ischemic attacks and two minor strokes) in a mean follow-up of 8 months, but no hemorrhage. Conclusions The stent-assisted coiling was successfully performed with acceptable range of ischemic events and without hemorrhage in all patients, including those who applied tailored medication. Low-dose prasugrel was effective for obtaining appropriate PRU values for initial medication as well as for clopidogrel-resistant patients. The genetic test did not provide reliable results in determining clopidogrel resistance.
Radiology, 2016
To identify and apply an optimized P2Y 12 reaction units (PRU) threshold for implementing modified antiplatelet preparation to prevent thromboembolic events in patients nonresponsive to clopidogrel (clopidogrel nonresponders) undergoing coil embolization of unruptured aneurysms and to evaluate the clinical validity. Materials and Methods: The optimal PRU threshold for prediction of thromboembolic events was determined with the Youden index in post hoc analysis of a previous, prospectively enrolled cohort of 165 patients in whom the antiplatelet regimen was not modified. This optimal PRU threshold was used to define clopidogrel nonresponders in a prospective validation study of 244 patients. Standard preparation (aspirin, clopidogrel) was maintained for 126 patients responsive to clopidogrel (clopidogrel responders, 51.6%), and modified preparation (aspirin, prasugrel) was prescribed prior to embolization for 118 clopidogrel nonresponders (48.4%). Fiftyseven clopidogrel nonresponders from the previous cohort who did not receive the modified preparation were included as a historical control group. Thromboembolic and bleeding events were compared among groups by using logistic regression analysis.
Clopidogrel resistance "Live" � the risk of stent thrombosis should be evaluated before procedures
Thrombosis Journal, 2009
Every year, millions of people undergo percutaneous coronary intervention (PCI) with intracoronary stent implantation. A patient from the PRAGUE-8 trial (Optimal pre-PCI clopidogrel loading: 600 mg before every coronary angiography vs. 600 mg in the cath-lab only for PCI patients) is described who suffered from acute stent thrombosis. This patient did not have any relevant inhibition of platelet activation even after the 600 mg dose of clopidogrel. Dose uptitration would have been ineffective. New P2Y 12 receptor inhibitors are desperately needed. In the light of recently published data, the use of prasugrel may be considered as an alternative.
Vascular and Endovascular Surgery, 2020
Background: Platelet inhibitory therapy is prescribed to prevent arterial thromboembolism in patients with atherosclerotic disease. Although taken by millions of people, around 30% are resistant to the treatment they are being prescribed. Aims: To determine whether symptoms of cerebral ischemia, or pre-operative cerebral emboli, in patients admitted for a carotid endarterectomy were associated with resistance to aspirin or clopidogrel. Methods: Venous blood from 133 patients immediately before carotid endarterectomy (CEA) was analyzed for resistance to aspirin and clopidogrel by multiplate impedance aggregometry. The number of emboli/hour entering the ipsilateral middle cerebral artery was counted by transcranial Doppler (TCD) on the day before surgery in 33 of these patients. Results: Resistance was found in 21 (26.3%) of 100 patients taking aspirin and 14 (42%) of 33 taking clopidogrel. Mean (sd) residual platelet aggregation was significantly higher at 41.9(32) Au in patients who...
Advances in Interventional Cardiology, 2015
Introduction: Nowadays, clopidogrel and acetylsalicylic acid (ASA) have become routinely applied therapies in percutaneous coronary interventions (PCI) with stenting. Aim: Numerous variables can interfere with antiplatelet responsiveness, so we aimed to investigate the role of different variables associated with ASA or clopidogrel resistance in stable coronary artery disease. Material and methods: A total of 207 patients undergoing elective PCI were included in the analysis. All patients received a loading dose of clopidogrel and ASA during PCI procedure and followed by dual antiplatelet therapy. Clopidogrel and ASA resistance were measured by impedance aggregometry method. Results: Of the patients, 19.8% had clopidogrel resistance, 18.8% had ASA resistance, 9.2% had both clopidogrel and ASA resistance, and 71.5% were responsive to both drugs. In multivariate analysis, platelet count, angiotensin receptor blocker (ARB) use, and ASA resistance were independent variables associated with clopidogrel resistance, and clopidogrel resistance was the only variable associated with ASA resistance. In differentiating whether clopidogrel resistance exists or not, optimum ASA aggregometry response cutoff values were specified, and in differentiating whether ASA resistance exists or not, optimum clopidogrel aggregometry response cutoff values were specified. Conclusions: In this study, there was a higher incidence of low responsiveness to ASA when there was a low response to clopidogrel, and vice versa. Angiotensin receptor blocker use, platelet count, and ASA resistance were independent variables associated with clopidogrel resistance. Clopidogrel resistance was the only independent variable associated with ASA resistance. Angiotensin receptor blocker use seems to an independent risk factor for clopidogrel resistance in this study, but this result needs to be verified in other studies.