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

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  • 1 Departments of Neurosurgery and
  • 2 Neurology, University of Texas Health Science Center at Houston, Texas
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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 subarachnoid hemorrhage would also benefit from periprocedural antiplatelet therapy.

METHODS

The authors reviewed a prospective registry of 169 patients with endovascularly treated intracranial aneurysms 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 aneurysm 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, cardiovascular 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 intracranial hemorrhage, 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 hemorrhages.

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.

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 subarachnoid hemorrhage would also benefit from periprocedural antiplatelet therapy.

METHODS

The authors reviewed a prospective registry of 169 patients with endovascularly treated intracranial aneurysms 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 aneurysm 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, cardiovascular 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 intracranial hemorrhage, 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 hemorrhages.

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.

Functional outcomes for patients with aneurysmal subarachnoid hemorrhage (aSAH) have improved in the past 2 decades, likely due in part to the availability and refinement of neurosurgical and endovascular treatment options.16 Because ruptured aneurysms are increasingly treated via coil embolization, preventing periprocedural complications will become more and more important. To date, the primary complication of coil embolization is a thromboembolic event (TEE).5,8,12,19 In the multicenter, prospective Clinical and Anatomical Results in the Treatment of Ruptured Intracranial Aneurysms (CLARITY) registry, TEEs occurred in 13.3% of patients, with 4.2% of patients suffering permanent neurological disability or even death from such events.6

In patients with unruptured intracranial aneurysms, increasing evidence supports the use of periprocedural antiplatelet therapy to prevent TEEs, including data from a recent randomized clinical trial.11,14,20,27 Whether periprocedural antiplatelet therapy should also be used in patients with ruptured aneurysms is less clear. Antiplatelet therapy—even if used for brief periods—would theoretically predispose aSAH patients to additional hemorrhagic complications, and such bleeding may not be tolerated in those with an already reduced neurological and hemodynamic reserve. That being said, several observational studies have suggested that aSAH patients are at an even higher risk of TEEs than patients with unruptured aneurysms.5,23 A Cochrane review has suggested improved outcomes in antiplatelet-treated aSAH patients,9 whereas a post hoc analysis of the International Subarachnoid Aneurysm Trial (ISAT) data has not.25 Furthermore, it is unclear if periprocedural antiplatelet therapy would be beneficial in all aSAH patients or only those at particularly high risk of a TEE during and after coiling.

The purpose of our study was 1) to define a subset of patients with ruptured aneurysms at a relatively higher risk for TEE and 2) to evaluate whether periprocedural aspirin would prevent clinically significant TEEs in such patients without increasing the risk of hemorrhagic complications.

Methods

This study was approved by The University of Texas Health Science Center at Houston Committee on Human Research.

For the first part of our study, we reviewed a prospective registry of all patients with cerebral aneurysms endovascularly treated in the period from 2008 to 2012. We excluded patients on outpatient and/or preprocedural antiplatelet or anticoagulant agents, patients who underwent stent-assisted coil embolization, patients whose coiling was complicated by a high-grade coil protrusion (Grade II or III, with the loop or coil protruding into more than half of the parent artery diameter, as described elsewhere,1 because we did not believe that there was clinical equipoise regarding antiplatelet therapy in patients with high-grade coil protrusions), and Hunt and Hess (HH) Grade V aSAH patients (as it would be challenging to assess neurological deterioration as defined in our primary outcome in a Grade V patient). In all cases, aneurysm coiling had been performed by a single endovascular surgeon (P.R.C.).

Our primary outcome was a TEE in the early periprocedural period, that is, during and 72 hours after coiling. Such an event was defined as a transient ischemic attack or ischemic stroke with evidence of infarction on CT or diffusion-weighted MRI in a vascular territory referential to the site of the treated aneurysm. A period of 72 hours after coiling was used to exclude patients with delayed neurological deterioration due to cerebral vasospasm or delayed cerebral ischemia rather than a TEE. We divided the registry into patients with our primary outcome of interest and those without. Descriptive statistics were used to delineate aneurysm features evident during angiography that were associated with a periprocedural TEE in this cohort. We defined a “high-risk” feature as any feature with a p value < 0.20 on the univariate analysis.

For the second part of our study, we performed a controlled before-and-after study to determine whether periprocedural acetylsalicylic acid (aspirin) (ASA) would reduce the rate of TEEs during and 72 hours after coiling in ruptured aneurysm patients with a relatively higher risk for such events, for example, patients with at least 1 of the high-risk angiographic features identified from the registry review. In Group 1, the treatment group, consecutive patients received intraprocedural ASA at a dose of 650 mg. Specifically, aspirin was given via nasogastric tube near the end of the coiling procedure. After coiling, the treatment group continued to receive ASA at a dose of 325 mg daily for a total of 14 days. Group 2, the control group, was enrolled subsequent to the patients in Group 1 and comprised consecutive aSAH patients with high-risk aneurysm features seen on angiography who were not treated with aspirin or any other antiplatelet (or anticoagulant) agent for the duration of their hospital stay. Patient exclusions were identical to those used in the first part of the study (detailed above).

All aneurysm coil embolization procedures were conventional and performed with the aid of general anesthesia. Regardless of whether patients were in Group 1 or Group 2, all of them were given an intravenous heparin bolus of 70–100 U/kg 5 minutes prior to coil embolization; intraprocedurally, heparin was continuously infused for a goal activated clotting time (ACT) of 2.5 to 3 times their baseline ACT. Heparin was postprocedurally reversed with protamine in all patients except those who developed a thrombus during coiling. In the patients with intraprocedural thrombus formation, ReoPro at a dose of 5 mg was infused through a microcatheter positioned proximal to the thrombus; thrombus resolution occurred in all patients without the need for further intervention.

The primary outcome in our controlled study remained a clinically significant TEE (transient ischemic attack or ischemic stroke) during the early periprocedural period (during and 72 hours after coiling). Secondary outcomes included periprocedural intracranial hemorrhage (ICH; those occurring during and 14 days after coiling) and major systemic bleeding as defined by the Thrombolysis in Myocardial Infarction (TIMI) bleeding criteria.15 Descriptive statistics (Pearson chi-square or Fisher's exact test for categorical variables; Student t-test or Wilcoxon test for continuous variables) were used to compare the baseline demographics and our primary and secondary outcomes of interest. Logistic regression analysis was performed to determine if antiplatelet use was independently associated with a reduced risk of periprocedural TEE. All analyses were conducted using Stata statistical software, version 13 (StataCorp LP). Statistical significance was set at p < 0.05.

Results

For the first part of our study, 169 patients from our registry of cerebral aneurysms treated with coil embolization 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 developed 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 atherosclerosis of the parent vessel (p = 0.19). These features are illustrated in Fig. 1.

FIG. 1.
FIG. 1.

Angiographic features associated with periprocedural TEEs: wide aneurysm neck (> 4 mm, A), Grade I protrusion—coil or loop protrudes into the lumen less than half of the parent arterial diameter (B), small parent artery diameter (< 1.5 mm, C), a branch incorporated into the sac or neck of the aneurysm (D), intraprocedural thrombus formation (arrow, E), and intracranial atherosclerosis of the parent vessel (F).

For the second part of our study, we consecutively enrolled 66 aSAH patients with at least 1 of the 6 high-risk aneurysm features into Group 1, the periprocedural aspirin 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. Enrollment 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 are summarized in Table 1. The aspirin-treated group was fairly similar to the control group, although there were significantly greater proportions of patients with HH Grade I, HH Grade IV, and internal carotid artery aneurysms in the ASA-treated group than in the control group (p = 0.04 and 0.001). Cardiovascular risk factors were similar, except for a history of smoking (higher in the aspirin-treated group, p = 0.05). Balloon-assisted coil embolization was performed nearly equally in the 2 study groups: in 75.8% of the aspirin-treated group versus 76.9% of the control group (p = 0.93).

TABLE 1.

Baseline characteristics and TEE rate in high-risk aSAH patients receiving periprocedural aspirin versus controls

VariableNo. (%)p Value
Aspirin-Treated GroupControl Group
No. of patients6613
Mean age, yrs (SD)53.58 (13.2)55.85 (11.4)0.56
Sex (M/F)16 (24.2)/50 (75.8)4 (30.7)/9 (69.3)0.62
Cardiovascular risk factors
  Smoking35 (53)3 (23.1)0.05
  DM8 (12.1)2 (15.3)0.74
  HTN41 (62.1)10 (76.9)0.31
  Hyperlipidemia12 (18.2)1 (7.6)0.36
  CAD9 (13.6)00.15
HH grade0.04
  I60
  II123
  III299
  IV191
Fisher grade0.17
  110
  222
  36311
  400
Aneurysm location0.001
  ACA216
  ICA40
  MCA92
  Posterior circulation325
Aneurysm size0.48
  <10 mm56 (84.8)12 (92.3)
  ≥10 mm10 (15.2)1 (7.7)
BACE50 (75.8)10 (76.9)0.93
Intraprocedural thrombus formation2 (3)1 (7.6)0.43
  EVD51 (77.3)8 (61.5)0.06
  VPS21 (31.8)3 (23.1)0.53
  TEE7 (10.6)7 (53.8)0.001

ACA = anterior cerebral artery; BACE = balloon-assisted coil embolization; CAD = coronary artery disease; DM = diabetes mellitus; HTN = hypertension; ICA = internal carotid artery; MCA = middle cerebral artery; VPS = ventriculoperitoneal shunt.

Boldface type indicates statistical significance.

Periprocedural TEEs developed in 14 (17.7%) of the high-risk ruptured aneurysm patients, 7 (10.6%) in the ASA-treated group and 7 (53.8%) in the control group. The higher TEE rate in the control group was highly statistically significant (p = 0.001; Table 1). The reduction in TEEs in the ASA-treated group continued to be statistically significant even when adjusted for age, sex, cardiovascular risk factors (smoking, diabetes, hypertension, dyslipidemia, coronary artery disease), and factors associated with TEE in other large studies (wide aneurysm neck, aneurysm size ≥ 10 mm18), with an adjusted OR of 0.16 (95% CI 0.03–0.80; Table 2).

TABLE 2.

Multivariate analysis of factors independently associated with TEE in high-risk aSAH patients

VariableAdjusted OR95% CI
Aspirin administration0.160.03–0.8
Age1.010.95–1.08
Sex0.360.07–1.72
Smoking0.710.15–3.33
DM2.160.33–13.88
HTN2.120.45–9.98
Hyperlipidemia0.180.01–2.87
CAD1.810.17–19.45
Wide aneurysm neck0.370.08–1.57
Aneurysm size ≥10 mm3.780.59–24.17

Boldface type indicates statistical significance.

In terms of non-ICH bleeding complications, 2 patients (3.0%) in the ASA-treated group versus 1 (7.7%) in the control group suffered a gastrointestinal bleed (minor, requiring transfusion but with a hemoglobin decline < 5 g/dl). There were no major bleeding episodes or retroperitoneal hemorrhages in either group. Periprocedurally, there were no symptomatic ICHs or aneurysm rebleeds in either group. Among patients with external ventricular drains (EVDs), we did find an increase in the number of asymptomatic, minor (< 1 cm) EVD track hemorrhages in the ASA-treated group (29.4% vs 12.5% in the control group, p = 0.02). On the other hand, only 3.9% of patients in the ASA-treated group versus 12.5% of controls developed an EVD track hemorrhage > 1 cm (p = 0.3; Table 3).

TABLE 3.

Bleeding complications in aspirin-treated patients versus controls

ComplicationAspirin-Treated Group (%)Control Group (%)p Value
Retroperitoneal hematoma00
Major bleeding00
GI bleeding, minor*2 (3)1 (7.7)0.42
Aneurysm rebleed00
sICH00
Minor EVD track hemorrhage (<1 cm)15 (29.4)1 (12.5)0.02
EVD track hemorrhage >1 cm2 (3.9)1 (12.5)0.3

GI = gastrointestinal; sICH = symptomatic intracranial hemorrhage.

Minor GI bleeding is clinically overt GI bleeding with a hemoglobin decline of 3 to < 5 g/dl.

For the EVD track hemorrhages, percentages represent patients with EVDs (51 in the aspirin-treated group, 8 in the control group).

Discussion

In our study cohort, we were able to identify 6 angiographic features conferring a relatively higher risk of TEEs during and 72 hours after coiling: wide aneurysm neck (> 4 mm), Grade I coil or loop protrusion, small parent artery diameter (< 1.5 mm), an incorporated branch, intraprocedural thrombus formation, and intracranial atherosclerosis of the parent vessel. When ruptured aneurysm patients with at least 1 of these high-risk features were given periprocedural aspirin, the rate of clinically evident TEEs was significantly reduced as compared with the rate in a consecutive group of patients who were not given antiplatelet therapy. This reduction in TEEs was independent of traditional cardiovascular risk factors and even factors previously associated with TEEs in other studies. Lastly, selective aspirin administration did not result in a greater frequency of major bleeding complications, either intracranially or systemically, in these aSAH patients.

Thrombus formation due to detachable coils primarily happens at the interface of the coil and luminal blood.10,17,26,28 Therefore, it is not surprising that several of the features associated with TEEs in our registry are ones that result in a larger coil-luminal interface—wide neck, coil or loop protrusion, small parent artery diameter (and therefore a relatively larger neck/parent artery ratio), and an incorporated branch. In other series large aneurysm size (≥ 10 mm) has been associated with periprocedural TEEs,8,18 though it is unclear if this association is independent of aneurysm neck size. Intraprocedural thrombus formation has been strongly associated with a subsequent infarct in our and others' studies; Ries et al. reported a stroke rate (as evident on CT) of 47.2% in patients with either ruptured or unruptured aneurysms who had developed a thrombus during coil embolization.20 Intracranial atherosclerosis of the parent vessel was also noted at a greater frequency in our patients who developed periprocedural TEEs, presumably because of the risk of embolization from catheter manipulation of a diseased parent vessel prone to embolic phenomena. As regards coil or loop protrusions, we can only comment on Grade I protrusions since patients with high-grade protrusions were excluded from our study because they were all invariably given periprocedural antiplatelet agents. Additional studies are needed to define periprocedural TEE rates in ruptured aneurysm patients with low-grade coil or loop protrusions versus rates in patients with high-grade protrusions.

Although several endovascular centers may administer antiplatelet agents to reduce periprocedural TEEs in ruptured aneurysm patients, there is currently no consensus regarding 1) optimal patient selection, 2) preferred antiplatelet agent, and 3) dosing protocol, including the dose, timing, and duration of antiplatelet administration. Several large studies have supported periprocedural antiplatelet agents to prevent TEEs in patients with unruptured aneurysms undergoing elective coil embolization,14,27 even a recent randomized clinical trial comparing modified and standard antiplatelet therapy in patients deemed to be at high risk for periprocedural TEEs because of high on-treatment platelet reactivity (HTPR).11 In this latter trial, 1 (1.6%) of 63 HTPR patients randomized to the treatment arm (modified antiplatelet therapy) developed a TEE as compared with 7 (11.1%) of 63 in the control arm (standard antiplatelet therapy); indeed, the rate of TEEs in the HTPR patients given the modified regimen mirrored the rate in the intrinsically lower-risk non-HTPR patients (1.6% vs 1.0%, respectively). That being said, the trial was performed in patients with unruptured aneurysms—clinically distinct from patients with ruptured aneurysms and SAH. In patients with ruptured aneurysms, other investigators have addressed intraprocedural thrombus formation and the reduction of intraprocedural TEEs with various regimens, for instance, intravenous aspirin20 or glycoprotein IIb/IIIa inhibitors.3,22 In our study, only 3 patients (3.8%) developed intraprocedural thrombi as evident on angiography, whereas 10.7% of our registry and 17.7% of our aSAH study group developed TEEs within hours to days of postcoiling. To the best of our knowledge, ours is the first controlled study (that is, with control versus treatment groups) to systematically define TEE reduction in the hours to days postcoiling in aspirin-treated ruptured aneurysm patients. And, as in the randomized trial in unruptured HTPR patients, antiplatelet therapy in our study of high-risk ruptured aneurysm patients reduced periprocedural TEEs to a level that mirrored that of our unselected population (10.6% in high-risk, aspirin-treated patients vs 10.7% in our general, untreated registry).

We chose to evaluate clinically significant TEEs—those in which patients' conditions deteriorated transiently or permanently with an imaging correlate of infarction. This definition of TEE is nearly identical to that used in the randomized trial of patients with unruptured aneurysms.11 Numerous studies have demonstrated even higher rates of clinically “silent,” imaging-evident periprocedural TEEs, as high as 61% of patients in one diffusion-weighted imaging study.2,7,21,24 Though the significance of these clinically silent infarcts is unclear, their occurrence can also be reduced by periprocedural antiplatelet therapy and thus warrants further investigation.

We specifically examined periprocedural aspirin administration in aSAH patients deemed to be high risk in order to minimize antiplatelet exposure to a select group rather than to all aSAH patients in whom the benefit of antiplatelets would be less clear. As opposed to unruptured aneurysm patients, ruptured aneurysm patients are at greater risk for hemorrhagic complications. For instance, approximately one-third of aSAH patients will develop hydrocephalus and require insertion of an EVD; multiple studies have described EVD-associated hemorrhage rates to be higher in patients on antiplatelet therapy.4,9,13 In our study, nearly 75% of patients had an EVD placed, probably because we are a tertiary care referral center and therefore have a greater proportion of high-grade patients (higher risk for hydrocephalus and the need for EVD placement). Indeed, we found an increase in minor EVD track hemorrhages (< 1 cm) in our aspirin-treated group as compared with that in our control group. Major periprocedural hemorrhages were rare—there were no cases of aneurysm rebleeding and no cases of symptomatic ICH; 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 hemorrhagic complications in our ASA-treated aSAH patients is similar to findings in previously published studies examining this. For instance, in one qualitative review of stent-assisted coiling complications—in which aSAH patients received dual antiplatelet therapies given the presence of an intracranial stent—ICHs occurred in 8% of the patients, the majority being EVD-associated hemorrhages of questionable clinical significance.4 Note that we did not see any major systemic hemorrhages in our ASA-treated group (as defined by TIMI bleeding criteria), which was similar to the lack of significant systemic bleeding in the randomized trial of unruptured aneurysm patients (even those who received a modified regimen of multiple antiplatelet agents).11

There are several limitations to this study. First, it is a single-center and indeed a single-operator study, though its single-operator nature minimizes technique-related confounders. Second, although the aspirin portion of our study is a controlled before-and-after study, it is not a randomized controlled trial and is therefore subject to multiple biases. Regarding selection bias, we believe it was minimized because we specifically compared the population characteristics of our treated and control arms; as detailed in Table 1, these characteristics were fairly comparable, with only HH grade and aneurysm location significantly differing between the 2 groups. Third, we terminated the control group in our study early given the high TEE rate noted during preliminary analysis; therefore, the number of patients in this group is significantly less than the number in the aspirin-treated group. Larger studies with similar numbers of patients in the treatment and control groups are needed to confirm our results, particularly to confirm an equal distribution of each of the high-risk features in both the treatment and control groups. Fourth and last, though we continued antiplatelet therapy for 14 days after coiling in our treatment group, the appropriate duration of periprocedural antiplatelets is entirely unclear. The rate of “delayed” periprocedural TEEs is also unclear as we only studied clinically significant TEEs within 72 hours of coiling, mainly because it would be challenging to distinguish cerebral vasospasm or delayed cerebral ischemia neurological deterioration and radiographic infarct from TEE-related deficits 4–14 days postprocedurally.

Conclusions

In summary, selective aspirin administration in ruptured aneurysm patients at highest risk for TEEs during and shortly after coiling significantly reduced the rate of clinically evident periprocedural thromboembolism. Aspirin administration in these patients did not result in any major hemorrhagic complications either intracranially or systemically, though there was an increase in minor, asymptomatic EVD-associated hemorrhage. Additional studies are needed to confirm these results and to further refine the exact subset of ruptured aneurysm patients who will benefit the most from antiplatelet therapy during and 72 hours after coiling.

Disclosures

This study was supported by the Weatherhead Foundation and the DiPaolo Family Fund.

Author Contributions

Conception and design: Edwards, Chen. Acquisition of data: Corona, Dannenbaum, Chen. Analysis and interpretation of data: Edwards, Jones, Sanzgiri, Corona, Chen. Drafting the article: Edwards, Jones. Critically revising the article: Edwards, Jones, Dannenbaum, Chen. Reviewed submitted version of manuscript: Edwards, Jones, Dannenbaum, Chen. Approved the final version of the manuscript on behalf of all authors: Edwards. Statistical analysis: Edwards, Sanzgiri. Administrative/technical/material support: Dannenbaum, Chen. Study supervision: Chen.

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    Mehran R, Rao SV, Bhatt DL, Gibson CM, Caixeta A, Eikelboom J, : Standardized bleeding definitions for cardiovascular clinical trials: a consensus report from the Bleeding Academic Research Consortium. Circulation 123:27362747, 2011

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 16

    Naval NS, Chang T, Caserta F, Kowalski RG, Carhuapoma JR, Tamargo RJ: Improved aneurysmal subarachnoid hemorrhage outcomes: a comparison of 2 decades at an academic center. J Crit Care 28:182188, 2013

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 17

    Pelz DM, Lownie SP, Fox AJ: Thromboembolic events associated with the treatment of cerebral aneurysms with Guglielmi detachable coils. AJNR Am J Neuroradiol 19:15411547, 1998

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 18

    Pierot L, Cognard C, Anxionnat R, Ricolfi F: Ruptured intracranial aneurysms: factors affecting the rate and outcome of endovascular treatment complications in a series of 782 patients (CLARITY study). Radiology 256:916923, 2010

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 19

    Pierot L, Wakhloo AK: Endovascular treatment of intracranial aneurysms: current status. Stroke 44:20462054, 2013

  • 20

    Ries T, Buhk JH, Kucinski T, Goebell E, Grzyska U, Zeumer H, : Intravenous administration of acetylsalicylic acid during endovascular treatment of cerebral aneurysms reduces the rate of thromboembolic events. Stroke 37:18161821, 2006

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 21

    Rordorf G, Bellon RJ, Budzik RE Jr, Farkas J, Reinking GF, Pergolizzi RS, : Silent thromboembolic events associated with the treatment of unruptured cerebral aneurysms by use of Guglielmi detachable coils: prospective study applying diffusion-weighted imaging. AJNR Am J Neuroradiol 22:510, 2001

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 22

    Sedat J, Chau Y, Gaudard J, Suissa L, Lachaud S, Lonjon M: Administration of eptifibatide during endovascular treatment of ruptured cerebral aneurysms reduces the rate of thromboembolic events. Neuroradiology 57:197203, 2015

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 23

    Seo DH, Yoon SM, Park HR, Shim JJ, Bae HG, Yun IG: Thromboembolic event detected by diffusion weighted magnetic resonance imaging after coil embolization of cerebral aneurysms. J Cerebrovasc Endovasc Neurosurg 16:175183, 2014

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 24

    Sim SY, Shin YS: Silent microembolism on diffusion-weighted MRI after coil embolization of cerebral aneurysms. Neurointervention 7:7784, 2012

  • 25

    van den Bergh WM, Kerr RSC, Algra A, Rinkel GJE, Molyneux AJ: Effect of antiplatelet therapy for endovascular coiling in aneurysmal subarachnoid hemorrhage. Stroke 40:19691972, 2009

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 26

    Workman MJ, Cloft HJ, Tong FC, Dion JE, Jensen ME, Marx WF, : Thrombus formation at the neck of cerebral aneurysms during treatment with Guglielmi detachable coils. AJNR Am J Neuroradiol 23:15681576, 2002

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 27

    Yamada NK, Cross DT III, Pilgram TK, Moran CJ, Derdeyn CP, Dacey RG Jr: Effect of antiplatelet therapy on thromboembolic complications of elective coil embolization of cerebral aneurysms. AJNR Am J Neuroradiol 28:17781782, 2007

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 28

    Yamane F, Ishihara S, Kohyama S, Kanazawa R, Ishihara H, Suzuki M, : Local thrombus formation at the coil-parent artery interface during endovascular coil embolization of cerebral aneurysms. J Neurol Surg A Cent Eur Neurosurg 73:358368, 2012

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation

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Contributor Notes

Correspondence Nancy J. Edwards, Departments of Neurosurgery and Neurology, University of Texas Health Science Center at Houston, 6431 Fannin St., Rm. 7.154, Houston, TX 77030. email: nancy.j.edwards@kp.org.

INCLUDE WHEN CITING Published online January 6, 2017; DOI: 10.3171/2016.9.JNS161340.

Disclosures This study was supported by the Weatherhead Foundation and the DiPaolo Family Fund.

  • View in gallery

    Angiographic features associated with periprocedural TEEs: wide aneurysm neck (> 4 mm, A), Grade I protrusion—coil or loop protrudes into the lumen less than half of the parent arterial diameter (B), small parent artery diameter (< 1.5 mm, C), a branch incorporated into the sac or neck of the aneurysm (D), intraprocedural thrombus formation (arrow, E), and intracranial atherosclerosis of the parent vessel (F).

  • 1

    Abdihalim M, Kim SH, Maud A, Suri MF, Tariq N, Qureshi AI: Short- and intermediate-term angiographic and clinical outcomes of patients with various grades of coil protrusions following embolization of intracranial aneurysms. AJNR Am J Neuroradiol 32:13921398, 2011

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    Cronqvist M, Wirestam R, Ramgren B, Brandt L, Nilsson O, Säveland H, : Diffusion and perfusion MRI in patients with ruptured and unruptured intracranial aneurysms treated by endovascular coiling: complications, procedural results, MR findings and clinical outcome. Neuroradiology 47:855873, 2005

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    Fiehler J, Ries T: Prevention and treatment of thromboembolism during endovascular aneurysm therapy. Klin Neuroradiol 19:7381, 2009

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    Hwang G, Huh W, Lee JS, Villavicencio JB, Villamor RBV Jr, Ahn SY, : Standard vs modified antiplatelet preparation for preventing thromboembolic events in patients with high on-treatment platelet reactivity undergoing coil embolization for an unruptured intracranial aneurysm: a randomized clinical trial. JAMA Neurol 72:764772, 2015

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  • 12

    Hwang G, Jung C, Park SQ, Kang HS, Lee SH, Oh CW, : Thromboembolic complications of elective coil embolization of unruptured aneurysms: the effect of oral antiplatelet preparation on periprocedural thromboembolic complication. Neurosurgery 67:743748, 2010

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  • 13

    Kung DK, Policeni BA, Capuano AW, Rossen JD, Jabbour PM, Torner JC, : Risk of ventriculostomy-related hemorrhage in patients with acutely ruptured aneurysms treated using stent-assisted coiling. J Neurosurg 114:10211027, 2011

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  • 14

    Matsumoto Y, Kondo R, Matsumori Y, Shimizu H, Takahashi A, Tominaga T: Antiplatelet therapy for prevention of thromboembolic complications associated with coil embolization of unruptured cerebral aneurysms. Drugs R D 12:17, 2012

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  • 15

    Mehran R, Rao SV, Bhatt DL, Gibson CM, Caixeta A, Eikelboom J, : Standardized bleeding definitions for cardiovascular clinical trials: a consensus report from the Bleeding Academic Research Consortium. Circulation 123:27362747, 2011

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 16

    Naval NS, Chang T, Caserta F, Kowalski RG, Carhuapoma JR, Tamargo RJ: Improved aneurysmal subarachnoid hemorrhage outcomes: a comparison of 2 decades at an academic center. J Crit Care 28:182188, 2013

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 17

    Pelz DM, Lownie SP, Fox AJ: Thromboembolic events associated with the treatment of cerebral aneurysms with Guglielmi detachable coils. AJNR Am J Neuroradiol 19:15411547, 1998

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 18

    Pierot L, Cognard C, Anxionnat R, Ricolfi F: Ruptured intracranial aneurysms: factors affecting the rate and outcome of endovascular treatment complications in a series of 782 patients (CLARITY study). Radiology 256:916923, 2010

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 19

    Pierot L, Wakhloo AK: Endovascular treatment of intracranial aneurysms: current status. Stroke 44:20462054, 2013

  • 20

    Ries T, Buhk JH, Kucinski T, Goebell E, Grzyska U, Zeumer H, : Intravenous administration of acetylsalicylic acid during endovascular treatment of cerebral aneurysms reduces the rate of thromboembolic events. Stroke 37:18161821, 2006

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 21

    Rordorf G, Bellon RJ, Budzik RE Jr, Farkas J, Reinking GF, Pergolizzi RS, : Silent thromboembolic events associated with the treatment of unruptured cerebral aneurysms by use of Guglielmi detachable coils: prospective study applying diffusion-weighted imaging. AJNR Am J Neuroradiol 22:510, 2001

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 22

    Sedat J, Chau Y, Gaudard J, Suissa L, Lachaud S, Lonjon M: Administration of eptifibatide during endovascular treatment of ruptured cerebral aneurysms reduces the rate of thromboembolic events. Neuroradiology 57:197203, 2015

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 23

    Seo DH, Yoon SM, Park HR, Shim JJ, Bae HG, Yun IG: Thromboembolic event detected by diffusion weighted magnetic resonance imaging after coil embolization of cerebral aneurysms. J Cerebrovasc Endovasc Neurosurg 16:175183, 2014

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 24

    Sim SY, Shin YS: Silent microembolism on diffusion-weighted MRI after coil embolization of cerebral aneurysms. Neurointervention 7:7784, 2012

  • 25

    van den Bergh WM, Kerr RSC, Algra A, Rinkel GJE, Molyneux AJ: Effect of antiplatelet therapy for endovascular coiling in aneurysmal subarachnoid hemorrhage. Stroke 40:19691972, 2009

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 26

    Workman MJ, Cloft HJ, Tong FC, Dion JE, Jensen ME, Marx WF, : Thrombus formation at the neck of cerebral aneurysms during treatment with Guglielmi detachable coils. AJNR Am J Neuroradiol 23:15681576, 2002

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 27

    Yamada NK, Cross DT III, Pilgram TK, Moran CJ, Derdeyn CP, Dacey RG Jr: Effect of antiplatelet therapy on thromboembolic complications of elective coil embolization of cerebral aneurysms. AJNR Am J Neuroradiol 28:17781782, 2007

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 28

    Yamane F, Ishihara S, Kohyama S, Kanazawa R, Ishihara H, Suzuki M, : Local thrombus formation at the coil-parent artery interface during endovascular coil embolization of cerebral aneurysms. J Neurol Surg A Cent Eur Neurosurg 73:358368, 2012

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation

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