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- N-[6-(4-butanoyl-5-methyl-1H-pyrazol-1-yl)pyridazin-3-yl]-5-chloro-1-[2-(4-methyl-piperazin-1-yl)-2-oxoethyl]-1H-indole-3-carboxamide (SAR216471), a Novel Intravenous and Oral, Reversible and Directly Acting P2Y12 Antagonist. [JOURNAL ARTICLE]
- J Med Chem 2014 Jul 30.
In the search of potential back-up of clopidogrel, we have initiated a HTS campaign designed to identify novel reversible P2Y12 antagonists. Starting from a hit with low micromolar binding activity, we report here, the main steps of the optimization process leading to the identification of the preclinical candidate, SAR216471. It is a potent, highly selective and reversible P2Y12 receptor antagonist and, by far, the most potent inhibitor of ADP-induced platelet aggregation among the P2Y12 antagonists described in the literature. SAR216471 displays potent in vivo antiplatelet and antithrombotic activities and has the potential to differentiate versus other antiplatelet agents.
- ECG of the Month: Unexpected Atrioventricular Conduction in High-Grade Atrioventricular Block. [JOURNAL ARTICLE]
- J La State Med Soc 2014 Mar-Apr; 166(1):75-77.
A 90-year-old man with a history of high blood pressure, a cerebrovascular accident without focal residua, dementia, and stage 3 chronic kidney disease went to the emergency department because of dizziness and near syncope. His medications were aspirin 81 mg qd, clopidogrel 75 mg qod, escitalopram oxalate 10 mg qd, quetiapine fumarate 25 mg qd, and memantine hydrochloride 10 mg qd. He had orthrostatic hypotension with supine blood pressure of 173/77 mmHg falling to 116/68 on standing, while pulse increased from 66 to 84 beats/min. He received IV fluid and returned home. Two days later, he saw his primary care physician because of episodes of dizziness and confusion. The Figure shows an electrocardiogram recorded during that visit.
- E-062 Intracranial Stenting for Atherosclerotic Disease with Aggressive Anti-platelet Therapy Management: A Consecutive Series of 154 Patients. [Journal Article]
- J Neurointerv Surg 2014 Jul.:A68.
Contemporary studies of intracranial stenting have utilised standard or aggressive medical therapy involving dual anti-platelet therapy, but have not evaluated anti-platelet therapy resistance as a component of treatment failure.The current study evaluates a prospective aggressive anti-platelet therapy management approach at two institutions in a consecutive series of 154 patients with symptomatic intracranial atherosclerotic disease (ICAD) treated with angioplasty and stenting with the Wingspan self-expanding nitinol stent. Anti-platelet medication therapeutic effects of aspirin and clopidogrel were measured prior to the procedures by platelet function assay, thromboelastography, aggregometry, or Accumetrics VerifyNow systems. Medications were adjusted or changed for subtherapeutic or supratherapeutic values with clopidogrel goal inhibition of 20-80% and aspirin reactive unit (ARU) less than 550.A total of 154 patients with symptomatic ICAD were treated from 2005 to 2014. The periprocedural complication rate was 3.9% (6/154) with 1 subarachnoid haemorrhage, 0 intraparenchymal haemorrhages, 5 perforator strokes, and no stent thrombosis. With a mean follow up of 2.3 years, the total ipsilateral stroke and death rate was 6.5% (10/154). The relative aspirin resistance rate was 7.8% and the relative clopidogrel resistance rate was 14.9% in this series. Eight of the patients (5.2%) required repeat angioplasty for symptomatic re-stenosis within the first year. The mean time to treatment was 10.7 days following the last stroke.With aggressive monitoring and management of anti-platelet medications, intracranial stenting complications of stent thrombosis and distal emboli can be reduced, although there is still a significant risk of perforator strokes, particularly in the middle cerebral artery and basilar distributions.M. Alexander: 1; C; Stryker Neurovascular. M. Nuno: None. J. Alexander: None. C. Agutos: None. W. Yu: 1; C; Stryker Neurovascular.
- E-052 Initial Institutional Experience with the Sceptre XC Balloon for the Endovascular Treatment of Cerebral Aneurysms. [Journal Article]
- J Neurointerv Surg 2014 Jul.:A62-3.
The Sceptre XC balloon is a novel extra-compliant dual-lumen balloon microcatheter designed for the endovascular treatment of cerebral aneurysms and arteriovenous malformations. This study aims to describe our initial institutional experience with the Sceptre XC balloon for the treatment of cerebral aneurysms.We performed a retrospective review of endovascular treatments of cerebral aneurysms with the Sceptre XC balloon at our institution from April 11th, 2012 until February 28th, 2014. Baseline patient and aneurysm characteristics, procedural variables, packing density, intra- operative and post-operative complications, and clinical outcomes using the modified Rankin Scale (mRS) were recorded.Forty-five patients underwent endovascular treatment of 54 cerebral aneurysms with assistance of the Sceptre XC balloon at our institution during the study period, 33 females (73%) and 12 males (27%), mean age 58.5 years (28-87 years). Fifty-three aneurysms were treated successfully (98.1%). Forty-two aneurysms were unruptured (78%) and 12 ruptured (22%); 5 aneurysms were recurrent (9%). Mean aneurysm size was 7 mm (median 6.3 mm, range 2-17 mm), mean neck size was 3.2 mm (median 2.8 mm, range 1-8.2 mm), mean dome-to-neck ratio was 1.8 (median 1.5, range 0.8-6.5). Aneurysm locations were 17 middle cerebral artery (32%), 13 anterior communicating artery (24%), 13 internal carotid artery (24%), 5 posterior communicating artery (9%), 2 pericallosal artery (4%) and 4 posterior circulation (7%). Balloon neck remodeling was performed in 49 aneurysms (91%), and stent-assistance was ultimately used in 3 aneurysms (5.6%). Three aneurysms were coiled directly through the Sceptre XC balloon (5.6%). Mean packing density was 39.4% (median 40%, range 12-72.2%). Immediate complete/near complete occlusion was achieved in 34 aneurysms (64%), residual neck in 7 aneurysms (13%) and residual sac in 12 aneurysms (23%). The table summarises the intra-operative and post-operative complications in our cohort. There were 3 intra-operative aneurysm ruptures (5.6%), 2 of previously-ruptured aneurysms (16.7%) and 1 of an unruptured aneurysm (2.4%), hemostasis was achieved by immediate balloon inflation in all cases and no patient developed a new neurological deficit. There was 1 distal branch vessel rupture during balloon inflation performed to reduce an intra-aneurysmal catheter loop for a wire exchange prior to stenting, resulting in the patient's death (2.2%). There was 1 ipsilateral intracerebral haemorrhage on post-operative day 2 in a hypertensive patient with a clopidogrel hyper-response leading to permanent contralateral hemiparesis (2.2%). Overall, 2 complications led to either a new permanent disabling neurological deficit or the patient's death (mRS ≥ 3, 4.4%).The Sceptre XC balloon is a valuable adjunctive device for the endovascular treatment of cerebral aneurysms, allowing high treatment success rates and packing densities, achievement of immediate hemostasis in the event of an intra-operative aneurysm rupture, and reduction in the overall need of stent-assistance for cerebral aneurysm treatment. neurintsurg;6/Suppl_1/A62-b/T1T1T1 Abstract E-052 Table 1 Intra-operative and post-operative complications Complication Number of occurrences Percent of aneurysms Complications resulting in new neurological deficit or death Percent of patients Intra-operative aneurysm rupture 3 5.6 0 Intra-operative distal vessel rupture 1 1.9 1 (death) 2.2 Any coil loop herniation into parent artery 7 13 1 (transient neurological deficit) 2.2 Coil loop herniation requiring stenting 1 1.9 0 Distal coil migration requiring coil retrieval 1 1.9 0 Post-operative ipsilateral infarction 1 1.9 1 (transient neurological deficit) 2.2 Post-operative ipsilateral intracerebral haemorrhage 1 1.9 1 (permanent hemiparesis) 2.2 Complications resulting in a new permanent disabling neurological deficit or death (mRS ≥ 3) 2 3.7 2 4.4 DISCLOSURES: J. Delgado Almandoz: 2; C; Microvention/Terumo, Covidien/ev3, Penumbra Inc. Y. Kadkhodayan: 2; C; Covidien/ev3. J. Fease: None. J. Scholz: None. A. Blem: None. K. Tran: None. B. Crandall: 2; C; Covidien/ev3.
- E-032 retrograde stent-assisted coil embolization of posterior communicating artery aneurysms. [Journal Article]
- J Neurointerv Surg 2014 Jul.:A52.
Endovascular coil embolization with or without stenting for the treatment of posterior communicating artery (PcommA) aneurysms is well established. However, if the PcommA originates from the base of the aneurysm, complete aneurysm obliteration with preservation of the PcommA may not be possible without the use of stent-assisted coiling (SAC). Depending on the angle of the origin of the PcommA, the use of an anterograde approach from the proximal carotid to distal PcommA may not be possible. However, the use of a retrograde approach from the PcommA to the distal carotid may be possible. We present three patients with wide necked PcommA aneurysms in which the neck of the aneurysm was approached retrograde through the posterior circulation to allow for SAC in order to allow for complete aneurysm obliteration with preservation of the PcommA.We retrospectively reviewed all cases of SAC performed by the senior author from June 2009-January 2014 to identify cases in which a PcommA aneurysm was treated via the retrograde approach. Three patients met the inclusion criteria. Medical records were reviewed for clinical course and imaging characteristics of the aneurysms. We also reviewed the operative reports and angiographic imaging of each endovascular treatment of each patient. All procedures were performed under general anesthesia and patients were started on Clopidogrel and Aspirin prior to stenting. Bifemoral access was obtained to allow 1)a coiling microcatheter access to the aneurysm via an anterograde approach through the carotid circulation, and 2)a stent delivery catheter across the neck of the aneurysm from the posterior communicating artery to the distal internal carotid artery via the posterior circulation. Following stent deployment, coil embolization was performed.Retrograde SAC was performed in three patients with an average age of 58±8 years. Two patients had previously treated aneurysms and one had an untreated aneurysm. The average size of filling aneurysm was 7.03±2.66 mm. The Enterprise® stent (Codman & Shurtleff, Inc., Raynham, MA) was used in all cases. Immediate angiographic results in two cases revealed no residual filling, and the third case had only trace residual filling. However at over 1-year follow-up angiography, this aneurysm was completely occluded. The patency of the PcommA was maintained in all three cases. There were no clinical complications associated with retrograde SAC in this series.The retrograde approach for SAC of PcommA aneurysms is a viable method to allow for complete aneurysm obliteration and preservation of the PcommA when other approaches would risk either incomplete obliteration with preservation of the PcommA or complete obliteration at the risk of occlusion of the PcommA. This approach may allow for complete and safe treatment of PcommA aneurysms that would have otherwise required microsurgical clipping for vessel reconstruction of the PcommA to maintain its patency. To our knowledge, we present the largest series to date of patients undergoing retrograde SAC of PcommA aneurysms.Retrograde stent assisted coiling is a useful technique which allows for complete aneurysm obliteration while maintaining the patency of the posterior communicating artery in select aneurysm of the posterior communicating artery.J. Caplan: 6; C; Stryker. J. Huang: None. R. Tamargo: None. M. Radvany: 1; C; Siemens Medical. 6; C; CeloNova Biosciences, Inc.
- E-019 flow diversion in the setting of subarachnoid haemorrhage. [Journal Article]
- J Neurointerv Surg 2014 Jul.:A46.
Flow diverters are increasingly used for treatment of intracranial aneurysms. In previous series, the Pipeline Embolization Device (PED) was used essentially for the treatment of unruptured aneurysms. Little is known about the use of the PED in ruptured aneurysms. We assess the safety and efficacy of the PED in the largest series of acutely ruptured aneurysms to date.A total of 20 patients with freshly ruptured aneurysms were treated with the PED between May 2011 and September 2013. Patients were loaded with aspirin and clopidogrel 8 h before the procedure. Platelet function was closely monitored throughout hospitalization using P2Y12 assays. Data on procedural safety was prospectively collected.Mean aneurysm size was 6.6 mm. Fifteen aneurysms (75%) arose from the anterior circulation. The number of PEDs used was 1.0 per aneurysm. Treatment was staged (initial coiling followed by coiling 1-2 weeks later) in 4 patients (20%). Adjunctive coiling was used in 6 cases (30%). There was only 1 complication (5%) in the series; this was a fatal intraoperative aneurysm dome rupture that occurred during adjunctive coil deployment. At the latest follow-up (mean, 6.1 months), all but one aneurysm were completely occluded. No aneurysm required further treatment. All except one patient (95%) achieved a favorable outcome (mRS 0-2).In this study, treatment of ruptured aneurysms with the PED was associated with low complication rates, high aneurysm occlusion rates, and excellent clinical outcomes. These findings suggest that the PED is a safe and effective alternative for ruptured aneurysms non amenable to conventional endovascular techniques or surgical clipping. A staged approach that entails initial aneurysm coiling followed by coiling 1-2 weeks later appears to be an adequate strategy in this setting.N. Chalouhi: None. M. Zanaty: None. D. Hasan: None. S. Tjoumarkis: None. R. Rosenwasser: None. P. Jabbour: None.
- O-007 Initial Institutional Experience Using a Target P2Y12 Reaction Units Range to Tailor the Clopidogrel Dose Administered to Patients with Cerebral Aneurysms Treated with the Pipeline Embolization Device and Stents. [Journal Article]
- J Neurointerv Surg 2014 Jul.:A4-5.
Variability in response to the P2Y12 receptor antagonists administered to patients with cerebral aneurysms treated with the Pipeline Embolization device (PED) or stents may play an important role in post-operative thromboembolic and haemorrhagic complications. We present our initial institutional experience using a target P2Y12 reaction units (PRU) range to tailor the clopidogrel dose administered.We retrospectively reviewed all patients who underwent endovascular treatment of cerebral aneurysms with the PED or stent-assistance at our institution from November 15th, 2011 until December 31st, 2013. Patient characteristics, P2Y12 receptor antagonist administered, thromboembolic and haemorrhagic complications, and clinical outcomes using the modified Rankin Scale (mRS) were recorded. The target PRU range was 60-240.Sixty-six patients were included, 49 females (74%) and 17 males (26%), mean age 57.5 years (25-82 years). Forty-six patients were treated with the PED (70%), 19 with a stent (29%) and 1 with a PED and a stent (1%). Eight patients were switched to prasugrel due to an initial clopidogrel hypo-response (12.1%). Forty patients underwent at least 1 adjustment to the clopidogrel dose due to either a hypo-response (PRU > 240) or hyper-response (PRU < 60) to the standard 75mg daily clopidogrel dose (61%), occurring on average 23 days after initiation of clopidogrel therapy. Among these, the first adjustment was made on average 8.5 days before the procedure in 13 patients (32.5%), on the day of the procedure in 6 patients (15%), and on average 23.7 days after the procedure in 21 patients (52.5%). After the first dose adjustment, the target 60-240 PRU range was reached in 71% of hypo-responders and 46% of hyper-responders. Table 1 illustrates the PRU change after the first clopidogrel dose adjustment. Table 2 illustrates the PRU change after subsequent clopidogrel dose adjustments. Table 3 illustrates the final P2Y12 receptor antagonist administered and associated thromboembolic and haemorrhagic complications leading to a permanent disabling neurological deficit (mRS ≥ 3).Overall, 73% of patients with cerebral aneurysms treated with the PED or stents required at least 1 adjustment to the clopidogrel dose or a switch to an alternate P2Y12 receptor antagonist to remain within the target 60-240 PRU range. neurintsurg;6/Suppl_1/A4-a/T1T1T1 Abstract O-007 Table 1 Change in PRU values after first clopidogrel dose adjustment Clopidogrel dose adjustment (DA) Number of patients Mean Pre-DA PRU Mean Post-DA PRU Mean PRU Change Patients within target 60-240 PRU range after DA Hypo-Responders, 75 mg daily to 150mg daily 7 264 182 -82 71% Hyper-Responders 33 21 69 +48 46% 75 mg daily to 75 mg every-other-day: 17 30 61 +31 35% 75 mg daily to 75 mg every-third-day: 13 13 71 +58 54% 75 mg daily to 75 mg every-Monday-and-Friday: 3 5 104 +99 67% neurintsurg;6/Suppl_1/A4-a/T2T2T2 Abstract O-007 Table 2 Change in PRU values after subsequent clopidogrel dose adjustments Clopidogrel dose adjustment (DA) Number of patients Mean days after clopidogrel initiation Mean days after procedure Mean PRU pre-DA Mean PRU post-DA Mean PRU change Patients within target 60-240 PRU range after DA Second DA: 24 40 25 29 92 +63 71% 150mg daily to 75mg daily (n = 1) or 75mg every-other-day (n = 1) 2 43 106 +63 100% 75 mg every-other-day to 75 mg every-third-day (n = 9) or 75 mg every-Monday-and-Friday (n = 3) 12 33 72 +39 58% 75 mg every-third-day to 75 mg every-Monday-and-Friday (n = 3), 75mg every-fifth-day (n = 4) or 75mg once-a-week (n = 1) 8 24 119 +95 88% 75 mg every-Monday-and-Friday to 75 mg once-a-week (n = 1) or 7.5 mg daily suspension (n = 1) 2 7 87 +80 50% Third DA 7 47 31 33 115 +82 57% 75 mg every-third-day to 75 mg every-fourth-day (n = 3) or 75 mg every-Monday-and-Friday (n = 3) 6 37 105 +68 50% 75 mg every-Monday-and-Friday to 75 mg once-a-week 1 9 178 +169 100% Fourth DA, 75 mg every-fourth-day to 75 mg every-fifth-day 1 39 29 42 155 +113 100% neurintsurg;6/Suppl_1/A4-a/T3T3T3 Abstract O-007 Table 3 Finalreceptor antagonist and major thromboembolic and haemorrhagic complications P2Y12 receptor antagonist dosing Number of patients (%) Major thromboembolic complications (mRS ≥ 3) PRU at time of complication (% with PRU >240) Major haemorrhagic complications (mRS ≥ 3) PRU at time of complication (% with PRU < 60) Clopidogrel, 150 mg daily 5 (8%) 1 (20%) 292 (100%) 1 (20%) 10 (100%) Clopidogrel, 75 mg daily 20 (30%) 0 n/a 0 n/a Clopidogrel, 75 mg every-other-day (n = 4) or 75 mg every-third-day (n = 7) 11 (17%) 0 n/a 0 n/a Clopidogrel, 75 mg every-fourth-day 2 (3%) 0 n/a 1 (50%) 58 (100%) Clopidogrel, 75 mg every-Monday-and-Friday 10 (15%) 0 n/a 0 n/a Clopidogrel, 75 mg every-fifth-day (n = 5) or 75 mg once-a-week (n = 3) 8 (12%) 0 n/a 0 n/a Clopidogrel suspension, 7.5 mg daily: 1 (1.5%) 0 n/a 0 n/a Prasugrel, 5 mg daily (n = 5) or 10mg daily (n = 3) 8 (12%) 0 n/a 2 (25%) 0, 185 (50%) Ticagrelor, 90 mg twice-a-day 1 (1.5%) 0 n/a 0 n/aJ. Delgado Almandoz: 2; C; Covidien/ev3, Microvention/Terumo, Penumbra Inc. Y. Kadkhodayan: 2; C; Covidien/ev3. J. Scholz: None. J. Fease: None. A. Blem: None. K. Tran: None. B. Crandall: 2; C; Covidien/ev3.
- P-008 Loading Doses of Aspirin and Clopidogrel Prior to Enterprise Stent-assisted Repair of Intracranial Aneurysm-A Single Center Experience. [Journal Article]
- J Neurointerv Surg 2014 Jul.:A24-5.
To prevent thromboembolic events in stent-assisted coiling of aneurysm, 5 to 7 days of being on both aspirin and clopidogrel is considered acceptable. For ruptured cases a loading doses of aspirin and clopidogrel is required at least two hours prior to stent placement. However, antiplatelet regimen in stent-assisted treatment of intracranial aneurysm is not universal and varies from center to center. There are no clear data to evaluate the use of loading dose of aspiring and clopidogrel in all consecutive cases.To evaluate the thromboembolic and haemorrhagic events associate with Enterprise stent-assisted repair of intracranial aneurysm using acute loading doses of aspirin and clopidogrel. Additionally, to determine the clinical and radiographic outcome of those patients who received enterprise stent and loading doses of antiplatelet.Consecutive patients underwent enterprise stent-assisted repair of aneurysm using loading doses of aspirin 324 mg (4 baby aspirin) and clopidogrel 300 mg 2 to 4 h prior to the procedure were enrolled. Patient's demographics including intra-operative and post operative events were recorded. The outcome was measured using national institute of health stroke scale (NIHSS) and modified Rankin Scale (mRS) score.58 patients (5 had baseline mRS 2) with mean age of 53 ± 13 underwent 67 stent-assisted procedures including two Y-stent neck reconstructions to treat 65 (2 ruptured cases) intracranial aneurysms. Stent deployment was achieved in all (98%) but one who underwent primary coiling of aneurysm. There was no intra-operative rupture or intracranial haemorrhage, but small perioperative left hemispheric subarachnoid haemorrhage was observed in one with right middle cerebral artery aneurysm. Intra-operative asymptomatic left MCA branch occlusion developed in one who had failed deployment of sent. Patient's MCA was recanalised using intra-arterial eptifibatide and discharged home in the following day with NIHSS 0. Post-operative thromboembolic events was observed in 2 cases (1.5%); first event developed day 2 with NIHSS 6 in a 42 years old woman with a giant right ICA giant aneurysm and who recovered completely (NIHSS 0, mRS 0) in 90days. The second event was visual distortion and diplopia (NIHSS 0) developed on day 2 in a 66 years old woman with basilar artery aneurysm. Her symptoms resolved completely and return to work. Immediate complete and near complete obliteration of aneurysm was observed in 66% and subtotal in 34%. There was no mortality or permanent disability in our series. 90 days mRS 0 and 1 was observed in 96% and mRS 2 in 4%.There was no mortality or permanent disability in our series. Good outcomeUsing loading doses of aspirin and clopidogrel in Enterprise stent-assisted repair of intracranial aneurysm is not only safe and feasible but associated with good clinical outcome. Therefore, loading doses of aspirin and clopidogrel is an alternative option for patients who are candidates for stent-assisted repair of intracranial aneurysm.Y. Lodi: None. V. Reddy: None. A. Devasenapathy: None. J. Chou: None. K. Shehades: None. K. Sethi: None. D. Galyon: None. S. Bajwa: None.
- P-007 Incidence and Management of Intimal Hyperplasia at 6 months after Flow Diversion for Intracranial Aneurysms. [Journal Article]
- J Neurointerv Surg 2014 Jul.:A24.
A new option in the treatment of large and complex intracranial aneurysms centerd along the cavernous/intradural segment of the ICA, proximal to the PCom artery, includes the utilization of flow-diverter devices. Intracranial stent/ flow diverter deployment in the treatment of aneurysm usually requires the administration of dual antiplatelet therapy for 3-12 months. Our usual protocol is to switch to mono-therapy with Aspirin after 6 months. We analyzed the results after continuing dual anti-platelet therapy based on the intimal hyperplasia (IH) noted on the 6 month follow-up cerebral angiography. The purpose of this study is to assess at 1-year follow-up the efficacy of mono or dual antiplatelet therapy in the management of in-PED IH observed at the 6-month cerebral angiogram.From October 2011 to February 2014, a total of 93 intracranial aneurysms in 83 patients (16 men and 67 women; age range, 19-85 years; mean age, 56.6 years) were treated with pipeline embolization device (PED) at our institution. A cone-beam CT (Philips, Allura Biplane FD20/20, Philips Medical, Best, Netherlands) was obtained using the angiography C-arm to assess for IH at FU angiographies. At 6-month follow-up (39 patients with 46 aneurysms) 8 cases of in-PED no-flow limiting minimal IH (< 10% vessel stenosis) were noted. In these patients medical management using continuation of dual antiplatelet therapy for additional 6 months up to a 1 year cerebral angiogram follow-up was used.In the 8 patients having IH at the 6 months angiogram, 4 patients have till now underwent a 1 year follow-up. Complete resolution of the intimal hyperplasia was seen in 3 patients, whereas a stable IH was noted in one patient. One year follow up angiography was available for an additional 11 patients, who did not have IH at the 6 month FU. The 1 year FU angiography in these patients demonstrated no interval development of IH after stopping Clopidogrel at the 6 month time period.In our experience the adjustment of antiplatelet drug therapy post endovascular PED treatment of intracranial aneurysm depending on 6 month follow up findings is strongly associated with complete Pipeline Embolization Device patency at 1-year follow-up. Furthermore in our experience cone-beam CT is an accurate and precise tool in the assessment of in-PED intimal hyperplasia development during follow-up.F. Massari: None. A. Puri: None. S. Hou: None. M. Perras: None. C. Brooks: None. C. Stout: None. M. Gounis: None. A. Wakhloo: None.
- P-006 Initial Response to Aspirin Therapy Measured with the PFA-100 Assay in Patients Undergoing Endovascular Treatment of Unruptured Cerebral Aneurysms. [Journal Article]
- J Neurointerv Surg 2014 Jul.:A23-4.
Recent studies have examined the variability in response to clopidogrel therapy in patients undergoing endovascular treatment of unruptured cerebral aneurysms; however, no study has systematically assessed patient response to aspirin therapy in this patient population. This study aims to determine the initial response to aspirin therapy in patients undergoing endovascular treatment of unruptured cerebral aneurysms.We retrospectively reviewed the results of platelet function testing in a cohort of patients who were started on aspirin therapy for the endovascular treatment of unruptured cerebral aneurysms at our institution from November 17th, 2011 until March 13th, 2014. Baseline patient characteristics, aspirin dosing and thromboembolic complications were recorded. Patient response to aspirin therapy was assessed with the PFA-100 assay before the procedure, with ≥50% inhibition defined as an appropriate platelet response.One-hundred and seventeen patients were included in the study, 23 male (20%) and 94 female (80%), mean age 56 years (25-84 years). The patients included in this cohort comprised 52.5% of patients who underwent treatment of an unruptured cerebral aneurysm at our institution during the study period. Forty-eight patients were active smokers (41%), 72 had a history of hypertension (62%) and 6 diabetes mellitus (5%). Sixty-two patients were treated with simple or balloon-assisted coiling (53%), 43 with the Pipeline Embolization Device (37%) and 12 with a stent (10%). Fifty-three patients were started on 325 mg aspirin (45%), 50 on 81mg enteric-coated aspirin (43%), and 14 on 81 mg non-enteric-coated aspirin (12%). Mean number of aspirin doses before the initial PFA-100 test was 11.5 (median 9, range 3-29). Overall, mean initial platelet inhibition was 68.2% (median 70.5%, range 20.5-94.6%), with a significantly-lower mean inhibition in patients taking 81mg enteric-coated aspirin (62.5%) compared to those taking 81 mg non-enteric-coated aspirin (72.1%, p-value 0.049) and 325 mg aspirin (72.5%, p-value 0.001). Overall, 13 patients were considered to be non-responders to aspirin therapy in the initial PFA-100 test (11.1%), most of whom were taking 81mg enteric-coated aspirin (9, 69%). There was a significantly-increased likelihood of an initial non-response to aspirin therapy among patients taking 81 mg enteric-coated aspirin (18%) compared to those taking 81 mg non-enteric-coated aspirin (7.1%) and 325 mg aspirin (5.7%, p-value 0.04). In multivariate logistic regression analysis, an 81 mg enteric-coated aspirin dose was the only independent predictor of an initial non-response to aspirin therapy in our cohort (odds ratio 0.52, 95% confidence interval 0.28-0.98, p-value 0.043). There were 7 thromboembolic complications in our cohort (6%), none of which caused a permanent disabling neurological deficit or death. All of the patients who experienced a thromboembolic complication had demonstrated an appropriate platelet response to aspirin therapy in pre-procedure testing.Performing pre-procedure platelet function testing in patients taking 81 mg enteric-coated aspirin to ensure an adequate platelet response to aspirin therapy may be prudent prior to undertaking endovascular treatment of an unruptured cerebral aneurysm.J. Delgado Almandoz: 2; C; Covidien/ev3, Microvention/Terumo. Y. Kadkhodayan: 2; C; Covidien/ev3. J. Scholz: None. J. Fease: None. A. Blem: None. K. Tran: None. B. Crandall: 2; C; Covidien/ev3.