Hemorrhagic complications after prasugrel (Effient) therapy for vascular neurointerventional procedures

Abstract

IntroductionDual antiplatelet therapy (DAPT) with aspirin and a thienopyridine (eg, clopidogrel) prevents stent related thromboembolic events in cardiac patients and is frequently utilized during neurointerventional surgery. However, recent data suggest that many patients exhibit clopidogrel resistance. Prasugrel—a newer thienopyridine—lowers the rate of cardiac stent thromboses in clopidogrel non-responders but a paucity of data exist regarding its safety and efficacy in neurointerventional surgery.MethodsAll patients undergoing neurointerventional surgery by a single interventionalist (CJM) over a 20 month period were retrospectively identified. Charts were reviewed for pre- and post-procedural DAPT regimens, pre-procedural coagulation parameters and procedural complications.Results76 patients received pre- and post-procedural DAPT for endovascular treatment of an intracerebral aneurysm, dural arteriovenous fistula or intra/extracranial arterial stenosis. 51 patients underwent 55 total procedures and were treated with aspirin/clopidogrel; 25 patients underwent 31 total procedures and were treated with aspirin/prasugrel. Those patients who received aspirin/prasugrel DAPT were identified pre-procedurally to be clopidogrel non-responders. Both treatment groups had a similar percentage of patients undergoing aneurysm coiling, stent assisted aneurysm coiling, aneurysm Onyx embolization, aneurysm pipeline embolization device treatment, extra/intracranial carotid artery angioplasty and stenting, and dural arteriovenous fistula coil embolization. A total of eight (9.3%) hemorrhagic complications were observed, two (3.6%) in the aspirin/clopidogrel group and six (19.4%) in the aspirin/prasugrel group (p=0.02). No differences were noted in hemorrhage rates for each procedure between treatment groups, nor were there any differences in thrombotic complications between groups.ConclusionOur results suggest that DAPT with aspirin/prasugrel may predispose to a higher risk of hemorrhage during neurointerventional surgery compared with DAPT with aspirin/clopidogrel.

Last-Recorded P2Y12 Reaction Units Value Is Strongly Associated with Thromboembolic and Hemorrhagic Complications Occurring Up to 6 Months after Treatment in Patients with Cerebral Aneurysms Treated with the Pipeline Embolization Device

“…21 In our cohort, 26% of patients were considered clopidogrel hyporesponders in preprocedural testing using a PRU cutoff of Ͼ200 (using a PRU cutoff of Ͼ240, 21% of patients would have been considered clopidogrel hyporesponders). The proportion of clopidogrel hyporesponders in our cohort was lower than that reported by Akbari et al 22 (32.9%) and Lee et al 23 (42.9%) in patients undergoing various types of neurointerventional procedures also tested with VerifyNow using a Ͻ40% "P2Y12% inhibition" cutoff. Although 4 patients in our cohort experienced nondisabling thromboembolic complications with last-recorded PRU values of Ͻ240 (including a delayed asymptomatic PED thrombosis and a delayed perforator infarction), the patient with the major disabling thromboembolic complication had a last-recorded PRU value of Ͼ240 (PRU 292).…”

“…Elective PED deployment is not undertaken until the patient is within the 60 -240 target PRU range in preprocedural testing performed no earlier than the day before the procedure. Due to the increased risk of major hemorrhagic complications with prasugrel encountered by our group and reported by Akbari et al, 22 and the occurrence of a major ipsilateral ICH on postoperative day 20 in a patient receiving a 5-mg daily prasugrel dose in our cohort (PRU 185), we no longer administer prasugrel to patients considered clopidogrel hyporesponders or who must undergo urgent/emergent PED procedures. Patients who must undergo urgent/emergent PED procedures are started on ticagrelor before the procedure (180 mg ϫ 1, then 90 mg twice a day) without P2Y12 receptor inhibition testing and are transitioned to clopidogrel on postoperative day 30 following the protocol described in Table 3.…”

Clopidogrel Resistance in Neurovascular Stenting: Correlations between Light Transmission Aggregometry, VerifyNow, and the Multiplate

“…14 In another study that included 67 patients in various clinical conditions, including intracranial bleeding caused by arteriovenous malformation and aneurysm rupture, the use of aspirin and prasugrel in clopidogrel-resistant patients was associated with an increased risk of hemorrhagic complications over that of aspirin and clopidogrel therapy (19.4% vs 3.6%, respectively; P ϭ .02). 15 Additional studies in the setting of neurovascular stent placement with these alternative drug administrations and homogeneous study conditions, including postprocedural platelet-inhibition testing, are required. Dose elevation to 150 mg of clopidogrel daily may be a treatment alternative.…”

The Use of Prasugrel and Ticagrelor in Pipeline Flow Diversion

“…Approximately 30% of patients exhibit anti-platelet resistance. 1 Insufficient platelet inhibition in CYP2C19 heterozygotes causes this variability in the response to clopidogrel. Several centers have replaced clopidogrel with different anti-aggregation drugs like prasugrel or ticagrelor in the management of these resistant cases.…”