Yasha Kadkhodayan

Pre-procedure P2Y12 reaction units value predicts perioperative thromboembolic and hemorrhagic complications in patients with cerebral aneurysms treated with the Pipeline Embolization Device

Background There is wide variability in the reported incidence of perioperative thromboembolic (0–14%) and hemorrhagic (0–11%) complications after Pipeline Embolization Device (PED) procedures for cerebral aneurysm treatment, which could be partly due to differences in patient response to the P2Y12 receptor antagonist administered while the PED endothelializes. This study aims to identify an optimal pre-procedure P2Y12 reaction units (PRU) value range and determine the independent predictors of perioperative thromboembolic and hemorrhagic complications after PED procedures. Methods We recorded patient and aneurysm characteristics, P2Y12 receptor antagonist administered, pre-procedure PRU value with VerifyNow, procedural variables and perioperative thromboembolic and hemorrhagic complications up to postoperative day 30 after PED procedures at our institution during an 8-month period. Perioperative complications were considered major if they caused a permanent disabling neurological deficit or death. Multivariate regression analysis was performed to identify independent predictors of perioperative complications in our cohort. Results Forty-four patients underwent 48 PED procedures at our institution during the study period. There were eight thromboembolic and hemorrhagic perioperative complications in our cohort (16.7%), four of which were major (8.3%). A pre-procedure PRU value of <60 or >240 (p=0.02) and a technically difficult procedure (p=0.04) were independent predictors of all perioperative complications. A pre-procedure PRU value of <60 or >240 (p=0.004) and a history of hypertension (p=0.03) were independent predictors of major perioperative complications. Conclusions In our cohort, a pre-procedure PRU value of <60 or >240 was the strongest independent predictor of all and major perioperative thromboembolic and hemorrhagic complications after PED procedures.

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

BACKGROUND AND PURPOSE: A recent study identified a preprocedural P2Y12 reaction units value of <60 or >240 as a strong independent predictor of perioperative thromboembolic and hemorrhagic complications after treatment of cerebral aneurysms with the Pipeline Embolization Device. This study aimed to determine whether a last-recorded P2Y12 reaction units value of <60 or >240 predicts thromboembolic and hemorrhagic complications up to 6 months after treatment of cerebral aneurysms with the Pipeline Embolization Device in the same patient cohort. MATERIALS AND METHODS: We recorded patient and aneurysm characteristics, P2Y12 receptor antagonist administered, P2Y12 reaction units value with VerifyNow, procedural variables, and thromboembolic and hemorrhagic complications up to 6 months after Pipeline Embolization Device procedures at our institution during an 8-month period. Complications causing a permanent disabling neurologic deficit or death were considered major. Multivariate regression analysis was performed to identify independent predictors of thromboembolic and hemorrhagic complications. RESULTS: Forty-four patients underwent 48 Pipeline Embolization Device procedures at our institution during the study period. There were 11 thromboembolic and hemorrhagic complications up to 6 months after treatment in our cohort (22.9%), 5 of which were major (10.4%). A last-recorded P2Y12 reaction units value of <60 or >240 was the only independent predictor of all (P = .002) and major (P = .03) thromboembolic and hemorrhagic complications in our cohort. Most patients (71%) required, on average, 2 adjustments to the dose or type of P2Y12 receptor antagonist to remain within the 60–240 target P2Y12 reaction units range. CONCLUSIONS: In our cohort, a last-recorded P2Y12 reaction units value of <60 or >240 was the only independent predictor of all and major thromboembolic and hemorrhagic complications up to 6 months after Pipeline Embolization Device procedures.

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

Introduction Dual 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. Methods All 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. Results 76 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. Conclusion Our results suggest that DAPT with aspirin/prasugrel may predispose to a higher risk of hemorrhage during neurointerventional surgery compared with DAPT with aspirin/clopidogrel.

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

Background and purpose Variability in response to clopidogrel therapy is increasingly being recognized as an important factor in thromboembolic and hemorrhagic complications encountered after neurointerventional procedures. This study aims to determine the variability in response to clopidogrel therapy and associated complications in patients undergoing endovascular treatment of unruptured cerebral aneurysms. Methods We recorded baseline patient characteristics, co-administered medications, P2Y12 reaction units (PRU) values with VerifyNow, clopidogrel dosing, and thromboembolic and hemorrhagic complications in patients undergoing endovascular treatment of unruptured cerebral aneurysms at our institution during a 19 month period. Results 100 patients were included in the study, 76 women and 24 men, mean age 57.3 years. 15 patients exhibited an initial clopidogrel hypo-response (PRU >240) and 21 patients an initial clopidogrel hyper-response (PRU <60). 36 patients had a follow-up VerifyNow test performed without changes to the standard 75 mg daily clopidogrel dose, which demonstrated that 59% of patients who had initially been within the target 60–240 PRU range exhibited a delayed conversion to clopidogrel hyper-response. In our cohort, a clopidogrel hypo-response was associated with a significantly increased risk of thromboembolic complications in patients undergoing cerebral aneurysm treatment with stent assistance or the pipeline embolization device (60%, p=0.003), while a clopidogrel hyper-response was associated with a significantly increased risk of major hemorrhagic complications in all patients undergoing endovascular treatment of cerebral aneurysms (11%, p=0.016). Conclusions We found wide and dynamic variability in response to clopidogrel therapy in patients undergoing endovascular treatment of unruptured cerebral aneurysms, which was significantly associated with thromboembolic and major hemorrhagic complications in our cohort.

Comparison of Enterprise With Neuroform Stent-Assisted Coiling of Intracranial Aneurysms

OBJECTIVE The Enterprise stent is the first closed-cell stent designed to treat wide-necked intracranial aneurysms. Advantages of the design can include improvement in keeping coils within an aneurysm and the ability of the stent to be recaptured. We compared the technical and clinical complications of the Enterprise stent with the open-cell Neuroform stent, its primary alternative. SUBJECTS AND METHODS Patients undergoing Enterprise and Neuroform stent-assisted aneurysm coiling were enrolled in prospective registries starting in March 2007 and February 2003, respectively. All consecutive patients through December 2011 were included. Deployment success and difficulty, stent movement and misplacement, and procedural complications were compared. RESULTS Enterprise deployment success was high (108 of 115 attempts, 93.9%) with 102 aneurysms receiving a stent compared with Neuroform (173 of 214 attempts, 80.8%, p = 0.001) with 163 aneurysms. Enterprise was easier to deploy (1.7% vs 15.9% difficult deployment, p < 0.0001). There were no significant differences in the rates of stent movement, misplacement, or symptomatic hemorrhage. Symptomatic thromboembolic events, however, were more frequent with the Enterprise stent (8.7% vs 1.4%, p = 0.0021). The Enterprise stent enabled treatment of 10 additional aneurysms that could not be treated with Neuroform and had a higher rate of immediate aneurysm occlusion (87.3% vs 73.0%, p = 0.0058). CONCLUSION Enterprise was easier to deploy and enabled treatment of additional aneurysms; however, there were more thromboembolic complications. On the basis of these findings, we prefer to use the Neuroform stent first and rely on the Enterprise stent as an easy-to-deliver backup for stent-assisted coiling.

Diagnostic Yield of Catheter Angiography in Patients with Subarachnoid Hemorrhage and Negative Initial Noninvasive Neurovascular Examinations

These authors explored the diagnostic yield of DSA in patients with SAH and previously negative CTA or MRA. A total of 55 patients who presented with diffuse SAH, perimesencephalic SAH, or sulcal SAH received CTA (n= 47) or MRA (n= 8). Despite normal findings on CTA or MRA, DSA showed vascular lesions in 11% of patients with diffuse SAH and in 1 patient with sulcal SAH. The investigators concluded that DSA is a valuable tool in patients with diffuse or sulcal SAH in whom previous noninvasive examinations are negative. BACKGROUND AND PURPOSE: The yield of DSA in patients with SAH and negative initial noninvasive neurovascular examinations (CTA or MRA) is not well-understood. This study aimed to determine the yield of DSA for the detection of causative vascular lesions in this clinical scenario. MATERIALS AND METHODS: We examined the yield of DSA for the detection of causative vascular lesions in a cohort of patients presenting to our institution with SAH and negative initial noninvasive neurovascular examinations during a 5-year period. Two experienced neuroradiologists independently evaluated the NCCT to determine the SAH pattern (diffuse, perimesencephalic, or peripheral sulcal) and the catheter angiograms to assess the presence of a causative vascular lesion. RESULTS: Fifty-five patients were included in the study, with a mean age of 58.2 years (median, 58 years; range, 25–88 years). Twenty-eight patients were men (50.9%), and 27 were women (49.1%). The initial noninvasive examination was a CTA in 47 patients (85.5%) and an MRA in 8 patients (14.5%). Thirty-three patients had diffuse SAH (60%); 11, perimesencephalic SAH (20%); and 11, peripheral sulcal SAH (20%). DSA demonstrated a causative vascular lesion in 6 patients (10.9%), 5 of whom had diffuse SAH (yield of 15.2%) and 1 of whom had peripheral sulcal SAH (yield of 9.1%). No causative vascular lesions were found in patients with perimesencephalic SAH. CONCLUSIONS: DSA is a valuable tool in the evaluation of patients with diffuse and peripheral sulcal SAH who have negative initial noninvasive neurovascular examinations, demonstrating a causative vascular lesion in 15.2% and 9.1% of patients, respectively.

Endovascular and Surgical Treatment of Unruptured MCA Aneurysms: Meta-Analysis and Review of the Literature

Introduction. The best treatment for unruptured middle cerebral artery (MCA) aneurysms is unclear. We perform a meta-analysis of recent publications to evaluate the results of unruptured MCA aneurysms treated with surgical clipping and endovascular coiling. Methods. A PubMed search for articles published between January 2004 and November 2013 was performed. The R statistical software package was used to create a random effects model for each desired incidence rate. Cochrans Q test was used to evaluate possible heterogeneity among the rates observed in each study. Results. A total of 1891 unruptured MCA aneurysms, 1052 clipped and 839 coiled, were included for analysis. The complete occlusion rate at 6–9 months mean follow-up was 95.5% in the clipped group and 67.8% in the coiled group (P < 0.05). The periprocedural thromboembolism rate in the clipping group was 1.8% compared with 10.7% in the aneurysms treated by coiling (P < 0.05). The recanalization rate was 0% for clipping and 14.3% for coiling (P = 0.05). Modified Rankin scores of 0–2 were obtained in 98.9% of clipped patients compared to 95.5% of coiled (NS). Conclusions. This review weakly supports clipping as the preferred treatment of unruptured MCA aneurysms. Clinical outcomes did not differ significantly between the two groups.

Impact of Vessel Choice on Outcomes of Polyvinyl Alcohol Embolization for Intractable Idiopathic Epistaxis

PURPOSE To determine the safety and efficacy of internal maxillary artery (IMA) and facial artery polyvinyl alcohol (PVA) embolization for treatment of refractory idiopathic epistaxis. MATERIALS AND METHODS From 1998-2011, 84 patients were referred for endovascular treatment of intractable idiopathic epistaxis. PVA (range, 180-300 μM) particles were used in all cases. One case required microcoils to prevent nontarget embolization. Medical records were reviewed for early recurrences and complications, which were correlated with the number of vessels receiving embolization using the Mantel-Haenszel χ(2)test for linear association; P<.05 was accepted for significance. RESULTS Vessels chosen for embolization were unilateral IMA in 8 patients, bilateral IMAs in 35 patients, bilateral IMAs with one facial artery in 32 patients, and bilateral IMAs and bilateral facial arteries in 9 patients. Early (<30 d) rebleeding requiring therapy occurred in nine patients (11%). Minor complications occurred in 22 patients (26%) and included mild facial or jaw pain, facial edema, headache, and transient ischemic attack. There was one major complication that consisted of facial skin sloughing and mild lip ulceration in a patient who had embolization of both IMAs and both facial arteries. A linear association was found when the number of vessels receiving embolization was correlated with both the rates of early recurrence (inversely, P = .04) and minor complications (P = .004). CONCLUSIONS An initial treatment strategy involving embolization of bilateral IMAs with or without embolization of facial arteries for refractory idiopathic epistaxis is safe and effective. Additional facial artery embolization reduces the risk of early recurrence but increases the risk of minor complications.

Symptomatic patients with intraluminal carotid artery thrombus: outcome with a strategy of initial anticoagulation

OBJECT The aim of this study was to define the optimal treatment for patients with symptomatic intraluminal carotid artery thrombus (ICAT). METHODS The authors performed a retrospective chart review of patients who had presented with symptomatic ICAT at their institution between 2001 and 2011. RESULTS Twenty-four patients (16 males and 8 females) with ICAT presented with ischemic stroke (18 patients) or transient ischemic attack ([TIA], 6 patients). All were initially treated using anticoagulation with or without antiplatelet drugs. Eight of these patients had no or only mild carotid artery stenosis on initial angiography and were treated with medical management alone. The remaining 16 patients had moderate or severe carotid stenosis on initial angiography; of these, 10 underwent delayed revascularization (8 patients, carotid endarterectomy [CEA]; 2 patients, angioplasty and stenting), 2 refused revascularization, and 4 were treated with medical therapy alone. One patient had multiple TIAs despite medical therapy and eventually underwent CEA; the remaining 23 patients had no TIAs after treatment. No patient suffered ischemic or hemorrhagic stroke while on anticoagulation therapy, either during the perioperative period or in the long-term follow-up; 1 patient died of an unrelated condition. The mean follow-up was 16.4 months. CONCLUSIONS Results of this study suggest that initial anticoagulation for symptomatic ICAT leads to a low rate of recurrent ischemic events and that carotid revascularization, if indicated, can be safely performed in a delayed manner.

Onyx is associated with poor venous penetration in the treatment of spinal dural arteriovenous fistulas

Background and purpose The use of Onyx has become the mainstream for the treatment of cranial dural arteriovenous fistulas (AVFs) and arteriovenous malformations, but the reported success for type I spinal dural arteriovenous fistulas (sDAVFs) remains limited. We review our experience with Onyx and report its limitations in the treatment of spinal AVFs. Materials and methods We retrospectively reviewed the Interventional Neuroradiology Procedure database at Washington University for cases of sDAVF embolization. Radiology reports were reviewed for fistula classification, treatment technique, and initial and follow-up results. Angiographic images were reviewed to confirm diagnosis, treatment, and penetration of embolisate into the draining vein. Results With the use of Onyx, sDAVFs were obliterated in six of seven patients at the time of treatment. Follow-up angiography confirmed sDAVF obliteration in two patients, and recurrence in two cases. Two patients had no follow-up. One patient not cured at the time of treatment was treated surgically. Of the nine total treatments, Onyx successfully crossed the nidus into the draining vein in only four cases. Successful venous embolization was facilitated with positioning of the microcatheter to less than 5 mm from the nidus in three of the four cases. The use of n-butyl cyanoacrylate (NBCA) resulted in venous penetration in eight of 10 cases, and short term follow-up cure in seven of 10 patients. Conclusions Our experience with Onyx for type I sDAVF embolization has been tempered by difficulty in achieving venous penetration and, consequently, a high rate of recurrence. For management of these fistulas, we favor NBCA or surgical treatment.