CLINICAL ARTICLE J Neurosurg 127:1326–1332, 2017

Antiplatelet therapy for the prevention of peri-coiling thromboembolism in high-risk patients with ruptured intracranial

Nancy J. Edwards, MD,1,2 Wesley H. Jones, MD,1 Aditya Sanzgiri, MPH,1 Juan Corona, MD,1 Mark Dannenbaum, MD,1 and Peng Roc Chen, MD1

Departments of 1Neurosurgery and 2Neurology, University of Texas Health Science Center at Houston, Texas

OBJECTIVE The most frequent procedural complication of the endovascular treatment of intracranial aneurysms is a thromboembolic event (TEE); in a subset of patients, such events will cause permanent neurological disability. In patients with unruptured aneurysms, increasing evidence supports the use of periprocedural antiplatelet therapy to prevent TEEs. The object of this study was to evaluate whether patients with ruptured aneurysms and would also benefit from periprocedural antiplatelet therapy. METHODS The authors reviewed a prospective registry of 169 patients with endovascularly treated intracranial aneu- rysms to delineate angiographic features associated with periprocedural TEEs. They then performed a controlled before- and-after study in 79 patients with ruptured aneurysms who were deemed to be at high risk for TEEs (for example, patients with at least 1 angiographic feature associated with TEEs) to evaluate whether selective aspirin administration would reduce the rate of periprocedural thromboembolism without increasing major hemorrhagic complications. RESULTS Six angiographic features were associated with periprocedural TEEs in the study cohort: wide neck, coil or loop protrusion, small parent artery diameter, an incorporated branch, intraprocedural thrombus formation, and intracranial parent vessel atherosclerosis. Aspirin administration to high-risk patients significantly decreased the rate of periprocedural TEEs, from 53.8% in the control group to 10.6% in the aspirin-treated group (p = 0.001). The reduction in TEEs in the aspirin-treated group continued to be statistically significant even when adjusted for age, sex, cardio- vascular risk factors (smoking, diabetes, hypertension, dyslipidemia, coronary artery disease), and factors associated with TEEs in other large studies (wide aneurysm neck, aneurysm size ≥ 10 mm), with an adjusted OR of 0.16 (95% CI 0.03–0.8). There were no major systemic hemorrhagic complications, and aspirin did not increase the risk of aneurysm rebleeding, symptomatic , or major external ventricular drain (EVD)–associated hemorrhage (p = 0.3), though there was an increase in asymptomatic, minor (< 1 cm) EVD-associated hemorrhage in the aspirin-treated group (p = 0.02). CONCLUSIONS The study findings suggest that for ruptured aneurysm patients with high-risk features, antiplatelet therapy can significantly reduce the rate of periprocedural TEE without increasing major systemic or intracranial hemor- rhages. https://thejns.org/doi/abs/10.3171/2016.9.JNS161340 KEY WORDS ruptured aneurysms; coiling; thromboembolic events; vascular disorders

unctional outcomes for patients with aneurysmal creasingly treated via coil embolization, preventing peri- subarachnoid hemorrhage (aSAH) have improved procedural complications will become more and more in the past 2 decades, likely due in part to the avail- important. To date, the primary complication of coil em- Fability and refinement of neurosurgical and endovascular bolization is a thromboembolic event (TEE).5,8,12,19 In the treatment options.16 Because ruptured aneurysms are in- multicenter, prospective Clinical and Anatomical Results

ABBREVIATIONS ASA = acetylsalicylic acid (aspirin); aSAH = aneurysmal subarachnoid hemorrhage; EVD = external ventricular drain; HH = Hunt and Hess; HTPR = high on-treatment platelet reactivity; ICH = intracranial hemorrhage; TEE = thromboembolic event; TIMI = Thrombolysis In Myocardial Infarction. SUBMITTED May 24, 2016. ACCEPTED September 13, 2016. INCLUDE WHEN CITING Published online January 6, 2017; DOI: 10.3171/2016.9.JNS161340.

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Unauthenticated | Downloaded 09/26/21 11:27 PM UTC ASA therapy for ruptured aneurysm patients in the Treatment of Ruptured Intracranial Aneurysms those without. Descriptive statistics were used to delineate (CLARITY) registry, TEEs occurred in 13.3% of patients, aneurysm features evident during angiography that were with 4.2% of patients suffering permanent neurological associated with a periprocedural TEE in this cohort. We disability or even death from such events.6 defined a “high-risk” feature as any feature with a p value In patients with unruptured intracranial aneurysms, in- < 0.20 on the univariate analysis. creasing evidence supports the use of periprocedural an- For the second part of our study, we performed a con- tiplatelet therapy to prevent TEEs, including data from a trolled before-and-after study to determine whether peri- recent randomized clinical trial.11,14,20,27 Whether peripro- procedural acetylsalicylic acid (aspirin) (ASA) would re- cedural antiplatelet therapy should also be used in patients duce the rate of TEEs during and 72 hours after coiling with ruptured aneurysms is less clear. Antiplatelet ther- in ruptured aneurysm patients with a relatively higher risk apy—even if used for brief periods—would theoretically for such events, for example, patients with at least 1 of the predispose aSAH patients to additional hemorrhagic com- high-risk angiographic features identified from the regis- plications, and such bleeding may not be tolerated in those try review. In Group 1, the treatment group, consecutive with an already reduced neurological and hemodynamic patients received intraprocedural ASA at a dose of 650 reserve. That being said, several observational studies mg. Specifically, aspirin was given via nasogastric tube have suggested that aSAH patients are at an even higher near the end of the coiling procedure. After coiling, the risk of TEEs than patients with unruptured aneurysms.5,23 treatment group continued to receive ASA at a dose of A Cochrane review has suggested improved outcomes in 325 mg daily for a total of 14 days. Group 2, the control antiplatelet-treated aSAH patients,9 whereas a post hoc group, was enrolled subsequent to the patients in Group analysis of the International Subarachnoid Aneurysm 1 and comprised consecutive aSAH patients with high- Trial (ISAT) data has not.25 Furthermore, it is unclear if risk aneurysm features seen on angiography who were not periprocedural antiplatelet therapy would be beneficial in treated with aspirin or any other antiplatelet (or anticoag- all aSAH patients or only those at particularly high risk of ulant) agent for the duration of their hospital stay. Patient a TEE during and after coiling. exclusions were identical to those used in the first part of The purpose of our study was 1) to define a subset of the study (detailed above). patients with ruptured aneurysms at a relatively higher risk All aneurysm coil embolization procedures were con- for TEE and 2) to evaluate whether periprocedural aspirin ventional and performed with the aid of general anesthe- would prevent clinically significant TEEs in such patients sia. Regardless of whether patients were in Group 1 or without increasing the risk of hemorrhagic complications. Group 2, all of them were given an intravenous heparin bolus of 70–100 U/kg 5 minutes prior to coil emboliza- Methods tion; intraprocedurally, heparin was continuously infused for a goal activated clotting time (ACT) of 2.5 to 3 times This study was approved by The University of Texas their baseline ACT. Heparin was postprocedurally re- Health Science Center at Houston Committee on Human versed with protamine in all patients except those who Research. developed a thrombus during coiling. In the patients with For the first part of our study, we reviewed a prospec- intraprocedural thrombus formation, ReoPro at a dose of 5 tive registry of all patients with cerebral aneurysms endo- mg was infused through a microcatheter positioned proxi- vascularly treated in the period from 2008 to 2012. We mal to the thrombus; thrombus resolution occurred in all excluded patients on outpatient and/or preprocedural an- patients without the need for further intervention. tiplatelet or anticoagulant agents, patients who underwent The primary outcome in our controlled study remained stent-assisted coil embolization, patients whose coiling a clinically significant TEE (transient ischemic attack or was complicated by a high-grade coil protrusion (Grade II ischemic ) during the early periprocedural period or III, with the loop or coil protruding into more than half 1 (during and 72 hours after coiling). Secondary outcomes of the parent artery diameter, as described elsewhere, be- included periprocedural intracranial hemorrhage (ICH; cause we did not believe that there was clinical equipoise those occurring during and 14 days after coiling) and regarding antiplatelet therapy in patients with high-grade major systemic bleeding as defined by the Thrombolysis coil protrusions), and Hunt and Hess (HH) Grade V aSAH in Myocardial Infarction (TIMI) bleeding criteria.15 De- patients (as it would be challenging to assess neurologi- scriptive statistics (Pearson chi-square or Fisher’s exact cal deterioration as defined in our primary outcome in a test for categorical variables; Student t-test or Wilcoxon Grade V patient). In all cases, aneurysm coiling had been test for continuous variables) were used to compare the performed by a single endovascular surgeon (P.R.C.). baseline demographics and our primary and secondary Our primary outcome was a TEE in the early peripro- outcomes of interest. Logistic regression analysis was per- cedural period, that is, during and 72 hours after coiling. formed to determine if antiplatelet use was independently Such an event was defined as a transient ischemic attack or associated with a reduced risk of periprocedural TEE. All ischemic stroke with evidence of infarction on CT or dif- analyses were conducted using Stata statistical software, fusion-weighted MRI in a vascular territory referential to version 13 (StataCorp LP). Statistical significance was set the site of the treated aneurysm. A period of 72 hours after at p < 0.05. coiling was used to exclude patients with delayed neuro- logical deterioration due to cerebral vasospasm or delayed cerebral ischemia rather than a TEE. We divided the regis- Results try into patients with our primary outcome of interest and For the first part of our study, 169 patients from our

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Unauthenticated | Downloaded 09/26/21 11:27 PM UTC N. J. Edwards et al. registry of cerebral aneurysms treated with coil emboliza- tion were analyzed. One hundred twenty-seven of these patients (75.1%) had ruptured aneurysms and 42 (24.8%) had unruptured aneurysms. The mean age of this cohort was 54.2 years, with 72.8% of patients being female. Clinically significant periprocedural TEEs (neurological deficit within 72 hours of aneurysm coiling with CT or diffusion-weighted imaging evidence of an infarct) were reported in 18 patients (10.6%). We compared aneurysm features evident during angiography in patients who de- veloped periprocedural TEEs with those in patients who did not have TEEs. On univariate analysis, 6 features were associated with TEEs in our study cohort: wide aneurysm neck (> 4 mm, p = 0.03), Grade I coil or loop protrusion (p = 0.12), small parent artery diameter (< 1.5 mm, p = 0.05), an incorporated branch (p = 0.19), intraprocedural thrombus formation (p = 0.02), and intracranial athero- sclerosis of the parent vessel (p = 0.19). These features are illustrated in Fig. 1. For the second part of our study, we consecutively en- rolled 66 aSAH patients with at least 1 of the 6 high-risk aneurysm features into Group 1, the periprocedural as- pirin group. As described in Methods, all patients in the ASA-treated group received an intraprocedural dose of aspirin (650 mg via nasogastric tube) along with aspirin at a dose of 325 mg daily for 14 days after coiling. We then enrolled 13 aSAH patients with at least 1 of the 6 high- risk aneurysm features into Group 2, the control group. Patients in the control group were not given any aspirin whatsoever, either intraprocedurally or otherwise. Enroll- ment in the control group was terminated early because of the significantly increased rate of TEEs noted during an interim analysis. The baseline clinical characteristics of these 79 patients FIG. 1. Angiographic features associated with periprocedural TEEs: are summarized in Table 1. The aspirin-treated group was wide aneurysm neck (> 4 mm, A), Grade I protrusion—coil or loop pro- fairly similar to the control group, although there were sig- trudes into the lumen less than half of the parent arterial diameter (B), nificantly greater proportions of patients with HH Grade small parent artery diameter (< 1.5 mm, C), a branch incorporated into I, HH Grade IV, and internal carotid artery aneurysms in the sac or neck of the aneurysm (D), intraprocedural thrombus formation the ASA-treated group than in the control group (p = 0.04 (arrow, E), and intracranial atherosclerosis of the parent vessel (F). and 0.001). Cardiovascular risk factors were similar, ex- cept for a history of smoking (higher in the aspirin-treated group, p = 0.05). Balloon-assisted coil embolization was There were no major bleeding episodes or retroperitoneal hemorrhages in either group. Periprocedurally, there were performed nearly equally in the 2 study groups: in 75.8% no symptomatic ICHs or aneurysm rebleeds in either group. of the aspirin-treated group versus 76.9% of the control Among patients with external ventricular drains (EVDs), group (p = 0.93). we did find an increase in the number of asymptomatic, Periprocedural TEEs developed in 14 (17.7%) of the minor (< 1 cm) EVD track hemorrhages in the ASA-treated high-risk ruptured aneurysm patients, 7 (10.6%) in the group (29.4% vs 12.5% in the control group, p = 0.02). On ASA-treated group and 7 (53.8%) in the control group. the other hand, only 3.9% of patients in the ASA-treated The higher TEE rate in the control group was highly sta- group versus 12.5% of controls developed an EVD track tistically significant (p = 0.001; Table 1). The reduction in hemorrhage > 1 cm (p = 0.3; Table 3). TEEs in the ASA-treated group continued to be statisti- cally significant even when adjusted for age, sex, cardio- vascular risk factors (smoking, diabetes, hypertension, Discussion dyslipidemia, coronary artery disease), and factors associ- In our study cohort, we were able to identify 6 an- ated with TEE in other large studies (wide aneurysm neck, giographic features conferring a relatively higher risk of aneurysm size ≥ 10 mm18), with an adjusted OR of 0.16 TEEs during and 72 hours after coiling: wide aneurysm (95% CI 0.03–0.80; Table 2). neck (> 4 mm), Grade I coil or loop protrusion, small par- In terms of non-ICH bleeding complications, 2 patients ent artery diameter (< 1.5 mm), an incorporated branch, (3.0%) in the ASA-treated group versus 1 (7.7%) in the con- intraprocedural thrombus formation, and intracranial ath- trol group suffered a gastrointestinal bleed (minor, requir- erosclerosis of the parent vessel. When ruptured aneurysm ing transfusion but with a hemoglobin decline < 5 g/dl). patients with at least 1 of these high-risk features were

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TABLE 1. Baseline characteristics and TEE rate in high-risk TABLE 2. Multivariate analysis of factors independently aSAH patients receiving periprocedural aspirin versus controls associated with TEE in high-risk aSAH patients No. (%) Variable Adjusted OR 95% CI Aspirin-Treated Control p Aspirin administration 0.16 0.03–0.8 Variable Group Group Value Age 1.01 0.95–1.08 No. of patients 66 13 Sex 0.36 0.07–1.72 Mean age, yrs (SD) 53.58 (13.2) 55.85 (11.4) 0.56 Smoking 0.71 0.15–3.33 Sex (M/F) 16 (24.2)/50 (75.8) 4 (30.7)/9 (69.3) 0.62 DM 2.16 0.33–13.88 Cardiovascular risk HTN 2.12 0.45–9.98 factors Hyperlipidemia 0.18 0.01–2.87 Smoking 35 (53) 3 (23.1) 0.05 CAD 1.81 0.17–19.45 DM 8 (12.1) 2 (15.3) 0.74 Wide aneurysm neck 0.37 0.08–1.57 HTN 41 (62.1) 10 (76.9) 0.31 Aneurysm size ≥10 mm 3.78 0.59–24.17 Hyperlipidemia 12 (18.2) 1 (7.6) 0.36 Boldface type indicates statistical significance. CAD 9 (13.6) 0 0.15 HH grade 0.04 I 6 0 II 12 3 blood.10,17,26,28 Therefore, it is not surprising that several of III 29 9 the features associated with TEEs in our registry are ones IV 19 1 that result in a larger coil-luminal interface—wide neck, Fisher grade 0.17 coil or loop protrusion, small parent artery diameter (and 1 1 0 therefore a relatively larger neck/parent artery ratio), and 2 2 2 an incorporated branch. In other series large aneurysm 3 63 11 size (≥ 10 mm) has been associated with periprocedural 8,18 4 0 0 TEEs, though it is unclear if this association is inde- Aneurysm location 0.001 pendent of aneurysm neck size. Intraprocedural thrombus ACA 21 6 formation has been strongly associated with a subsequent ICA 4 0 infarct in our and others’ studies; Ries et al. reported a MCA 9 2 stroke rate (as evident on CT) of 47.2% in patients with Posterior circulation 32 5 either ruptured or unruptured aneurysms who had devel- oped a thrombus during coil embolization.20 size 0.48 atherosclerosis of the parent vessel was also noted at a <10 mm 56 (84.8) 12 (92.3) greater frequency in our patients who developed peripro- ≥10 mm 10 (15.2) 1 (7.7) cedural TEEs, presumably because of the risk of embo- BACE 50 (75.8) 10 (76.9) 0.93 lization from catheter manipulation of a diseased parent Intraprocedural throm- 2 (3) 1 (7.6) 0.43 vessel prone to embolic phenomena. As regards coil or bus formation loop protrusions, we can only comment on Grade I pro- EVD 51 (77.3) 8 (61.5) 0.06 trusions since patients with high-grade protrusions were VPS 21 (31.8) 3 (23.1) 0.53 excluded from our study because they were all invari- TEE 7 (10.6) 7 (53.8) 0.001 ably given periprocedural antiplatelet agents. Additional studies are needed to define periprocedural TEE rates in ACA = anterior cerebral artery; BACE = balloon-assisted coil embolization; ruptured aneurysm patients with low-grade coil or loop CAD = coronary artery disease; DM = diabetes mellitus; HTN = hypertension; protrusions versus rates in patients with high-grade pro- ICA = internal carotid artery; MCA = middle cerebral artery; VPS = ventriculo- trusions. peritoneal shunt. Boldface type indicates statistical significance. Although several endovascular centers may adminis- ter antiplatelet agents to reduce periprocedural TEEs in ruptured aneurysm patients, there is currently no consen- sus regarding 1) optimal patient selection, 2) preferred given periprocedural aspirin, the rate of clinically evident antiplatelet agent, and 3) dosing protocol, including the TEEs was significantly reduced as compared with the rate dose, timing, and duration of antiplatelet administra- in a consecutive group of patients who were not given an- tion. Several large studies have supported periprocedural tiplatelet therapy. This reduction in TEEs was independent antiplatelet agents to prevent TEEs in patients with un- of traditional cardiovascular risk factors and even factors ruptured aneurysms undergoing elective coil emboliza- previously associated with TEEs in other studies. Lastly, tion,14,27 even a recent randomized clinical trial compar- selective aspirin administration did not result in a greater ing modified and standard antiplatelet therapy in patients frequency of major bleeding complications, either intra- deemed to be at high risk for periprocedural TEEs be- cranially or systemically, in these aSAH patients. cause of high on-treatment platelet reactivity (HTPR).11 Thrombus formation due to detachable coils pri- In this latter trial, 1 (1.6%) of 63 HTPR patients random- marily happens at the interface of the coil and luminal ized to the treatment arm (modified antiplatelet therapy)

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TABLE 3. Bleeding complications in aspirin-treated patients order to minimize antiplatelet exposure to a select group versus controls rather than to all aSAH patients in whom the benefit of an- Aspirin-Treated Control p tiplatelets would be less clear. As opposed to unruptured Complication Group (%) Group (%) Value aneurysm patients, ruptured aneurysm patients are at greater risk for hemorrhagic complications. For instance, Retroperitoneal hematoma 0 0 approximately one-third of aSAH patients will develop Major bleeding 0 0 hydrocephalus and require insertion of an EVD; multiple GI bleeding, minor* 2 (3) 1 (7.7) 0.42 studies have described EVD-associated hemorrhage rates 4,9,13 Aneurysm rebleed 0 0 to be higher in patients on antiplatelet therapy. In our sICH 0 0 study, nearly 75% of patients had an EVD placed, prob- ably because we are a tertiary care referral center and Minor EVD track hemorrhage 15 (29.4) 1 (12.5) 0.02 therefore have a greater proportion of high-grade patients (<1 cm)† (higher risk for hydrocephalus and the need for EVD EVD track hemorrhage >1 cm† 2 (3.9) 1 (12.5) 0.3 placement). Indeed, we found an increase in minor EVD GI = gastrointestinal; sICH = symptomatic intracranial hemorrhage. track hemorrhages (< 1 cm) in our aspirin-treated group as * Minor GI bleeding is clinically overt GI bleeding with a hemoglobin decline of compared with that in our control group. Major peripro- 3 to < 5 g/dl. cedural hemorrhages were rare—there were no cases of † For the EVD track hemorrhages, percentages represent patients with EVDs aneurysm rebleeding and no cases of symptomatic ICH; (51 in the aspirin-treated group, 8 in the control group). the occurrence of EVD track hemorrhages > 1 cm was similar in patients receiving ASA versus controls (2 vs 1 patient, respectively). The absence of major intracranial developed a TEE as compared with 7 (11.1%) of 63 in the hemorrhagic complications in our ASA-treated aSAH pa- control arm (standard antiplatelet therapy); indeed, the tients is similar to findings in previously published studies rate of TEEs in the HTPR patients given the modified examining this. For instance, in one qualitative review of regimen mirrored the rate in the intrinsically lower-risk stent-assisted coiling complications—in which aSAH pa- non-HTPR patients (1.6% vs 1.0%, respectively). That be- tients received dual antiplatelet therapies given the pres- ing said, the trial was performed in patients with unrup- ence of an intracranial stent—ICHs occurred in 8% of the tured aneurysms—clinically distinct from patients with patients, the majority being EVD-associated hemorrhages 4 ruptured aneurysms and SAH. In patients with ruptured of questionable clinical significance. Note that we did not aneurysms, other investigators have addressed intrapro- see any major systemic hemorrhages in our ASA-treated cedural thrombus formation and the reduction of intra- group (as defined by TIMI bleeding criteria), which was procedural TEEs with various regimens, for instance, in- similar to the lack of significant systemic bleeding in the travenous aspirin20 or glycoprotein IIb/IIIa inhibitors.3,22 randomized trial of unruptured aneurysm patients (even In our study, only 3 patients (3.8%) developed intraproce- those who received a modified regimen of multiple anti- dural thrombi as evident on angiography, whereas 10.7% platelet agents).11 of our registry and 17.7% of our aSAH study group de- There are several limitations to this study. First, it is a veloped TEEs within hours to days of postcoiling. To the single-center and indeed a single-operator study, though best of our knowledge, ours is the first controlled study its single-operator nature minimizes technique-related (that is, with control versus treatment groups) to system- confounders. Second, although the aspirin portion of atically define TEE reduction in the hours to days post- our study is a controlled before-and-after study, it is not coiling in aspirin-treated ruptured aneurysm patients. a randomized controlled trial and is therefore subject And, as in the randomized trial in unruptured HTPR pa- to multiple biases. Regarding selection bias, we believe tients, antiplatelet therapy in our study of high-risk rup- it was minimized because we specifically compared the tured aneurysm patients reduced periprocedural TEEs to population characteristics of our treated and control arms; a level that mirrored that of our unselected population as detailed in Table 1, these characteristics were fairly (10.6% in high-risk, aspirin-treated patients vs 10.7% in comparable, with only HH grade and aneurysm location our general, untreated registry). significantly differing between the 2 groups. Third, we We chose to evaluate clinically significant TEEs— terminated the control group in our study early given the those in which patients’ conditions deteriorated transiently high TEE rate noted during preliminary analysis; there- or permanently with an imaging correlate of infarction. fore, the number of patients in this group is significantly This definition of TEE is nearly identical to that used in less than the number in the aspirin-treated group. Larger the randomized trial of patients with unruptured aneu- studies with similar numbers of patients in the treatment rysms.11 Numerous studies have demonstrated even higher and control groups are needed to confirm our results, rates of clinically “silent,” imaging-evident periprocedural particularly to confirm an equal distribution of each of TEEs, as high as 61% of patients in one diffusion-weight- the high-risk features in both the treatment and control ed imaging study.2,7,21,24 Though the significance of these groups. Fourth and last, though we continued antiplatelet clinically silent infarcts is unclear, their occurrence can therapy for 14 days after coiling in our treatment group, also be reduced by periprocedural antiplatelet therapy and the appropriate duration of periprocedural antiplatelets thus warrants further investigation. is entirely unclear. The rate of “delayed” periprocedural We specifically examined periprocedural aspirin ad- TEEs is also unclear as we only studied clinically signifi- ministration in aSAH patients deemed to be high risk in cant TEEs within 72 hours of coiling, mainly because it

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Unauthenticated | Downloaded 09/26/21 11:27 PM UTC ASA therapy for ruptured aneurysm patients would be challenging to distinguish cerebral vasospasm or high on-treatment platelet reactivity undergoing coil embo- delayed cerebral ischemia neurological deterioration and lization for an unruptured intracranial aneurysm: a random- radiographic infarct from TEE-related deficits 4–14 days ized clinical trial. JAMA Neurol 72:764–772, 2015 12. Hwang G, Jung C, Park SQ, Kang HS, Lee SH, Oh CW, et postprocedurally. al: Thromboembolic complications of elective coil emboliza- tion of unruptured aneurysms: the effect of oral antiplatelet Conclusions preparation on periprocedural thromboembolic complication. Neurosurgery 67:743–748, 2010 In summary, selective aspirin administration in rup- 13. Kung DK, Policeni BA, Capuano AW, Rossen JD, Jabbour tured aneurysm patients at highest risk for TEEs during PM, Torner JC, et al: Risk of ventriculostomy-related hemor- and shortly after coiling significantly reduced the rate of rhage in patients with acutely ruptured aneurysms treated clinically evident periprocedural thromboembolism. Aspi- using stent-assisted coiling. J Neurosurg 114:1021–1027, rin administration in these patients did not result in any 2011 major hemorrhagic complications either intracranially 14. Matsumoto Y, Kondo R, Matsumori Y, Shimizu H, Taka- or systemically, though there was an increase in minor, hashi A, Tominaga T: Antiplatelet therapy for prevention of thromboembolic complications associated with coil emboli- asymptomatic EVD-associated hemorrhage. Additional zation of unruptured cerebral aneurysms. Drugs R D 12:1–7, studies are needed to confirm these results and to further 2012 refine the exact subset of ruptured aneurysm patients who 15. 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CP, Dacey RG Jr: Effect of antiplatelet therapy on thrombo- Author Contributions embolic complications of elective coil embolization of cere- Conception and design: Edwards, Chen. Acquisition of data: bral aneurysms. AJNR Am J Neuroradiol 28:1778–1782, Corona, Dannenbaum, Chen. Analysis and interpretation of data: 2007 Edwards, Jones, Sanzgiri, Corona, Chen. Drafting the article: 28. Yamane F, Ishihara S, Kohyama S, Kanazawa R, Ishihara H, Edwards, Jones. Critically revising the article: Edwards, Jones, Suzuki M, et al: Local thrombus formation at the coil-parent Dannenbaum, Chen. Reviewed submitted version of manuscript: artery interface during endovascular coil embolization of Edwards, Jones, Dannenbaum, Chen. Approved the final version cerebral aneurysms. J Neurol Surg A Cent Eur Neurosurg of the manuscript on behalf of all authors: Edwards. Statistical 73:358–368, 2012 analysis: Edwards, Sanzgiri. Administrative/technical/material support: Dannenbaum, Chen. Study supervision: Chen. Correspondence Nancy J. Edwards, Departments of Neurosurgery and Neurology, Disclosures University of Texas Health Science Center at Houston, This study was supported by the Weatherhead Foundation and the 6431 Fannin St., Rm. 7.154, Houston, TX 77030. email: DiPaolo Family Fund. [email protected].

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