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. 2020 Jul 29;26(5):532–538. doi: 10.1177/1591019920947878

Outcome of flow diverter placement for intracranial aneurysm with dual antiplatelet therapy and oral anticoagulant therapy

Takashi Fujii 1,✉, Hidenori Oishi 1,2, Kohsuke Teranishi 2, Kenji Yatomi 2, Kazumoto Suzuki 2, Hajime Arai 2
PMCID: PMC7645175  PMID: 32727310

Abstract

Purpose

Antiplatelet therapy initiated before flow diverter placement is effective for the prevention of ischemic complications. However, the effectiveness of oral anticoagulant treatment is unclear. This retrospective study evaluated the complications and obliteration rates after flow diverter placement in patients taking anticoagulants.

Methods

A total of 155 cases were treated by Pipeline Flex placement for unruptured large and giant cerebral aneurysms in our hospital between October 2015 and June 2019. The groups of 8 patients taking anticoagulants before operation and 147 patients not taking anticoagulants were compared.

Results

Clopidogrel oral dose (P = 0.002) was significantly lower in the anticoagulant group. Delayed aneurysm rupture (P = 0.002) and additional treatment (P = 0.009) rates were significantly higher and complete obliteration rate (P = 0.011) was lower in the anticoagulant group.

Conclusions

Additional oral anticoagulant administration before flow diverter placement does not reduce ischemic complications compared to dual antiplatelet therapy, but does increase hemorrhagic complications, especially delayed aneurysm rupture. Complete obliteration of the cerebral aneurysm is difficult to achieve in patients taking anticoagulants.

Keywords: Aneurysm, anticoagulant, stent, flow diverter

Introduction

The flow diverter is a new device for the endovascular treatment of cerebral aneurysms which are otherwise difficult to treat.1–5 The effectiveness of the flow diverter is now established, but the high metal coverage ratio may cause ischemic complications such as perforator occlusion or thromboembolism.67 Prevention of these ischemic complications during endovascular surgery requires preoperative administration of antiplatelet agents. In particular, stent-assisted coiling depends on dual antiplatelet therapy (DAPT) to achieve reliable platelet aggregation inhibitory effects.8–11 The flow diverter is intended to promote thrombus formation in the aneurysm by causing stagnation of the blood flow, in contrast to the conventional stent. Complete obliteration of the aneurysm depends on achieving both primary aggregation, thrombus formation due to the stent placement, and secondary aggregation, thrombus formation due to stagnant blood flow in the aneurysm. If secondary aggregation is more important for ischemic complication after flow diverter placement, oral anticoagulants are better than oral antiplatelet agents to avoid ischemic complications. On the other hand, oral anticoagulant administration will delay secondary aggregation, and so is less desirable for obtaining complete obliteration of the aneurysm. However, few studies have examined the effects of anticoagulant administration on cerebral aneurysms.12

This retrospective study examined the complications and obliteration rates after flow diverter placement in patients receiving anticoagulants.

Materials and methods

Patient and aneurysm characteristics

A total of 155 consecutive patients were treated using the Pipeline Flex device (Medtronic Neurovascular, Irvine, CA) for unruptured large and giant internal carotid artery aneurysms located from the petrous segment to the superior hypophyseal segment for the first time in our hospital between October 2015 and June 2019. Eight patients had been taking anticoagulants before Pipeline Flex placement. The patient characteristics, age, sex, location of cerebral aneurysm, size of dome and neck, presence or absence of cranial nerve symptoms, presence or absence of hypertension or dyslipidemia of history, oral clopidogrel dose, VerifyNow (Accumetrics Inc., San Diego, CA) results, platelet aggregation blood test results, angiographic follow-up duration, and HAS-BLED13 and CHA2DS2-VASc score14 were evaluated. The two groups of patients taking anticoagulants (anticoagulant group) and those not taking anticoagulants (non-anticoagulant group) were compared (Table 1).

Table 1.

Clinical characteristics of patients with intracranial aneurysms treated by flow diverter devices.

Parameters Anticoagulant group(n = 8) Non-anticoagulant group(n = 147) P value
Age, mean ± SD, years 71.4 ± 8.9 62.0 ± 13.7 0.071
Sex, male : female, n 1 : 7 13 : 134 0.540
Side, right : left, n 5 : 3 61 : 86 0.287
Location, cavernous segment : paraclinoid segment, n 6 : 2 76 : 71 0.283
Aneurysm size, mean ± SD, mm 14.6 ± 4.1 16.3 ± 6.4 0.580
Aneurysm neck size, mean ± SD, mm 9.1 ± 5.3 8.2 ± 4.4 0.585
Symptoms, n (%) 4 (50.0) 58 (39.5) 0.714
Thrombosed aneurysms, n (%) 0 (0.0) 3 (2.0) 1.000
Past history
 Hypertension, n (%) 2 (25.0) 51 (34.7) 0.716
 Dyslipidemia, n (%) 3 (37.5) 27 (18.4) 0.644
 Clopidogrel, mean ± SD, mg 50.0 ± 13.4 67.2 ± 18.5 0.002
VerifyNow (n = 57)
 ARU, mean ± SD 438.5 ± 30.4 422.2 ± 86.4 0.680
 PRU, mean ± SD 175.0 ± 56.6 192.0 ± 100.6 0.881
Platelet aggregation blood test
 Collagen, mean ± SD 54.1 ± 14.0 51.2 ± 11.5 0.659
 ADP, mean ± SD 52.5 ± 14.3 49.4 ± 9.8 0.464
Angiographic follow-up duration, mean ± SD, months 11.3 ± 6.1 13.4 ± 7.5 0.374
HAS-BLED score, mean ± SD 2.5 ± 0.9 1.9 ± 0.8 0.064
CHA2DS2-VASc score, mean ± SD 2.8 ± 1.0 2.0 ± 1.1 0.059
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ADP indicates adenosine diphosphate; ARU, aspirin reaction unit; DAPT, dual antiplatelet therapy; PRU, P2Y12 reaction unit; SD, standard deviation.

This study was approved by the institutional review board, and informed consent was exempted from the retrospective review. The procedures were performed in accordance with all relevant guidelines and regulations.

Endovascular procedures

Oral administration of dual antiplatelet agents, aspirin 100 mg and clopidogrel, and proton pump inhibitor were started at least 10 days before operation, regardless of whether anticoagulant was taken or not. The platelet aggregation blood test was performed using adenosine diphosphate and collagen reaction in all patients on the day before the operation. The VerifyNow test was performed at the beginning of this study but less often in the latter half due to cost effectiveness. The dose of clopidogrel was 25 mg, 50 mg, or 75 mg depending on the physique, results of the platelet aggregation blood test and VerifyNow test, or the presence or absence of oral anticoagulant administration.

Surgery was performed under general anesthesia in all patients. Heparin 5000 units was intravenously administered at insertion of the guiding sheath, and additionally as required to maintain the activated clotting time at 2–2.5 times the control value. All catheters were continuously perfused with heparinized saline. Additional coils were placed to promote thrombosis in aneurysms that could cause subarachnoid hemorrhage in the event of delayed aneurysm rupture. Cone-beam computed tomography was performed in addition to the usual angiography after placing the Pipeline Flex. Percutaneous transluminal angioplasty was also performed if malposition of the device was found. After the operation, general heparinization was allowed to reverse naturally, the sheath was removed, and hand pressure hemostasis was performed for several hours after the operation in all patients.

Postoperatively, head magnetic resonance (MR) angiography was performed in all patients, and diffusion-weighted imaging (DWI) was used to assess the presence of acute ischemic change. The presence or absence of complete obliteration and the mortality associated with the procedure were evaluated using distal parenchymal hemorrhage, symptomatic ischemic complications, delayed aneurysm rupture, additional treatment, postoperative cranial nerve symptoms worsening and improvement, and O’Kelly Marotta (OKM) scale.15 Changes in embolic state after operation were evaluated by angiography every 6 months. Clopidogrel administration was gradually reduced or discontinued depending on the angiography findings.

Statistical analysis

All statistical analyses were conducted utilizing EZR (Saitama Medical Center, Jichi Medical University, Omiya, Saitama, Japan), which is a graphical user interface for R (version 2.13.0; The R Foundation for Statistical Computing, Vienna, Austria). Values were expressed as the mean ± standard deviation. Differences between the two groups were analyzed by the Mann-Whitney U test or the Fisher exact test. Values of P < 0.05 were considered to indicate statistical significance.

Results

Evaluation of the patient characteristics showed that the clopidogrel oral dose (P = 0.002) was significantly lower in the anticoagulant group (Table 1). Mean age (P = 0.071), HAS-BLED score (P = 0.064), and CHA2DS2-VASc score (P = 0.059) were higher but not significantly.

Table 2 shows the outcome. Additional coiling was performed in one patient (12.5%) in the anticoagulant group, and 46 patients (31.3%) in the non-anticoagulant group. Postoperative DWI showed positive findings in 6 patients (75.0%) in the anticoagulant group, and 113 (76.9%) in the non-anticoagulant group. Distal parenchymal hemorrhage was observed in no patients in the anticoagulant group, and 5 patients (3.4%) in the non-anticoagulant group. Symptomatic ischemic complications were observed in no patients in the anticoagulant group, and 9 patients (6.1%) in the non-anticoagulant group. Delayed aneurysm rupture was observed in 2 patients (25%) in the anticoagulant group, but none in the non-anticoagulant group. Additional treatment was given to 3 patients (37.5%) in the anticoagulant group, and 7 patients (4.8%) in the non-anticoagulant group. Postoperative worsening of neurological symptoms was observed in 2 patients (25.0%) in the anticoagulant group, and 6 patients (4.1%) in the non-anticoagulant group. Improvement of postoperative neurological symptoms was observed in no patients in the anticoagulant group, but 29 patients (19.7%) in the non-anticoagulant group. Follow-up angiography was performed in 148 (95.5%) patients, including all in the anticoagulant group and 140 (95.2%) in the non-anticoagulant group. At the time of the final follow up, incomplete obliteration was found in 6 patients (75.0%) in the anticoagulant group, and 40 patients (28.5%) in the non-anticoagulant group. No procedure-related deaths occurred in this study. The anticoagulant group suffered more delayed aneurysm rupture (P = 0.002), required more additional treatment (P = 0.009), and had a lower rate of complete obliteration at final follow up (P = 0.011).

Table 2.

Outcome of patients with intracranial aneurysms treated by flow diverter devices.

Parameters Anticoagulant group (n = 8) Non-anticoagulant group (n = 147) Odds ratio P value
Additional coiling, n (%) 1 (12.5) 46 (31.3) 0.31 0.436
Postoperative DWI high intensity positive, n (%) 6 (75.0) 113 (76.9) 0.90 1.000
Postoperative distal parenchymal hemorrhage, n (%) 0 (0.0) 5 (3.4) 0.0 1.000
Postoperative symptomatic infarction, n (%) 0 (0.0) 9 (6.1) 0.0 1.000
Postoperative delayed aneurysm rupture, n (%) 2 (25.0) 0 (0.0) NA 0.002
Additional treatment, n (%) 3 (37.5) 7 (4.8) 11.6 0.009
Postoperative neurological worsening, n (%) 2 (25.0) 6 (4.1) 4.5 0.119
Postoperative neurological improvement, n (%) 0 (0.0) 29 (19.7) 0.0 0.353
OKM scale A, B, and C at final follow up, n (%) 6 (75.0) 40 (28.5) 7.4 0.011
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DWI indicates diffusion-weighted image; OKM, O’Kelly Marotta; NA, not available.

Discussion

Anticoagulant therapy is commonly used as a prophylactic for non-valvular atrial fibrillation, deep vein thrombosis, and pulmonary thromboembolism. In particular, atrial fibrillation is relatively frequently encountered in clinical settings in the field of neurosurgery due to its prevalence as a coexisting disease. Atrial fibrillation is more likely to occur in older patients,1617 so that minimally invasive endovascular treatment is particularly likely in patients with atrial fibrillation.

Previously, warfarin was the only oral medication for anticoagulant therapy. However, direct oral anticoagulants have recently been developed and offer better safety and efficacy compared to warfarin.1819 This study used HAS-BLED score13 as a risk assessment for hemorrhagic complications and CHA2DS2-VASc score14 as a risk assessment for ischemic complications (Table 3). A history of atrial fibrillation or pulmonary thrombus or high HAS-BLED and CHA2DS2-VASc scores were not significantly more common in the anticoagulant group. Hemorrhagic complications were significantly more common in the anticoagulant group. However, individual patients with delayed aneurysm rupture, that is hemorrhagic complications, did not have a particularly high HAS-BLED score. In addition, these scores showed no apparent correlation with the OKM scale (Table 3).

Table 3.

Anticoagulant therapy and outcomes in patients treated by flow diverter devices.

Case no. Sex Age Anticoagulant Dose (mg/day) Etiology HAS-BLED score CHA2DS2VASc score Additional coiling Delayed aneurysm rupture Final OKM
1 F 59 Rivaroxaban 10 AF 1 1 − − D
2 F 82 Apixaban 10 Pulmonary embolism 2 4 − + C
3 F 65 Apixaban 10 AF 4 4 + − D
4 M 67 Dabigatran 220 AF 3 2 − − C
5 F 68 Rivaroxaban 15 AF 2 2 − − B
6 F 74 Edoxaban 30 AF 3 3 − − C
7 F 70 Apixaban 5 AF 3 3 − − A
8 F 86 Apixaban 5 AF 2 3 − + B
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AF indicates atrial fibrillation; F, female; M, male.

This study showed that taking anticoagulants apparently did not reduce the incidence of ischemic complications or ischemic foci on postoperative head MR imaging. Unlike a conventional stent, the flow diverter promotes thrombus formation in the aneurysm due to blood flow stagnation resulting in more complete obliteration. Based on the results of this study, the thrombus in the aneurysm is unlikely to cause ischemic complications.

Interestingly, the present study showed that the complete obliteration rate at final follow up was significantly lower in the anticoagulant group, suggesting that thrombus formation due to blood flow stagnation after flow diverter placement was not promoted. In fact, the embolization state after one year in Case 5 was OKM scale B indicating poor embolization, despite confirmation of favorable eclipse sign after Pipeline Flex placement (Figure 1). Older age may be a predictor of poor embolic state following flow diverter placement,20 possibly related to the common use of oral anticoagulants in the elderly, who are more likely to have atrial fibrillation. The mechanism of cerebral aneurysm occlusion involves another important process, endothelialization, in addition to intra-aneurysmal thrombosis. Even if the intra-aneurysmal thrombosis was inadequate after the flow diverter placement, total obliteration may result if complete endothelialization has occurred.2122 Immediately after the device is placed, endothelialization gradually progresses from the side of the parent artery to the aneurysm neck.2324 In particular, endothelialization of the aneurysm neck requires adhesion of smooth muscle cells to the neck to form a scaffold. Endothelialization based on such a smooth muscle cell scaffold may be disrupted if no intracranial thrombus is present. Thrombus adherence to the stent was significantly lower using the Pipeline shield, but neointimal endothelialization was higher with the Pipeline shield.2526 Consequently, thrombus near the aneurysm is unlikely to promote endothelialization due to the molecular mechanism. The present study found that complete obliteration in the aneurysm was lower in the oral anticoagulant group, suggesting that endothelialization at the neck requires intra-aneurysmal thrombosis. If endothelialization in the oral anticoagulant group is impaired at the stent site, thrombotic complications may occur, so antiplatelet administration should be continued for longer than usual.27

Figure 1.

Figure 1.

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Case 5. (a) Right internal carotid angiogram showing a large intracranial aneurysm located on the cavernous segment. (b) Percutaneous transluminal angioplasty was performed after Pipeline Flex placement for the intracranial aneurysm. (c) Cone-beam computed tomography scan confirmed Pipeline Flex placement with good apposition, and eclipse sign in the aneurysm (white arrow). (d) Right internal carotid angiogram indicated O’Kelly Marotta scale B at 1 year after Pipeline Flex placement (black arrow).

Hemorrhagic complications, that is delayed aneurysm rupture, were more common in the anticoagulant group. The WOEST study and DUAL-PCI study of coronary disease treatment found that concomitant use of oral anticoagulants in addition to DAPT promotes hemorrhagic complications.1928 The mechanism of delayed aneurysm rupture may involve induction of an inflammatory response during the thrombotic process.29–32

The present study also suggests that red blood clots formed in the arterial wall may be ruptured by autolysis induced by the effect of anticoagulants, causing such an inflammatory response. Postoperative cranial nerve symptoms tended to worsen in the anticoagulant group, and no patients showed improvement. These results suggest that stagnation of blood flow in the aneurysm caused an inflammatory reaction in the aneurysm wall, but the blood flow into the aneurysm continued and the aneurysm did not shrink in the anticoagulant group. Such delayed aneurysm rupture can be prevented by additional coiling.3033 Additional coil embolization is performed as a policy of our institution, especially for paraclinoid aneurysms that may cause subarachnoid hemorrhage after rupture. Consequently, no case of postoperative subarachnoid hemorrhage associated with delayed aneurysm rupture occurred in this series. Case 2 with carotid cavernous fistula caused by delayed aneurysm rupture was treated by transvenous aneurysmal embolization (Figure 2).434 Only one case (Case 3) of the anticoagulant group with additional coiling did not suffer postoperative delayed aneurysm rupture, and achieved complete obliteration at the final follow up. Flow diverter placement with additional coiling or parent artery occlusion if tolerated will be effective for the prevention of aneurysm rupture and minimize complications.

Figure 2.

Figure 2.

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Case 2. (a) Right internal carotid angiogram showing a large intracranial aneurysm located on the cavernous segment. (b) Percutaneous transluminal angioplasty was performed after Pipeline Flex placement for the intracranial aneurysm. (c) Carotid cavernous fistula was caused by delayed aneurysm rupture 7 days after the Pipeline Flex placement. (d) Carotid cavernous fistula was almost completely diminished after transvenous intracranial embolization with only slight reflux to the inferior petrosal sinus (black arrow).

This study has some limitations. Firstly, this is a retrospective study. Secondly, only 8 cases of oral anticoagulant administration were included, although the prevalence of oral anticoagulant administration is relatively high. A large-scale randomized control study will be required to examine the effects of anticoagulants after placement of the flow diverter. Thirdly, patients in the anticoagulant group combined the effects of three antithrombotic agents, which contain anticoagulants in addition to DAPT. However, the effects of one anticoagulant and one antiplatelet agent have not been studied. In a cardiovascular study, hemorrhagic complications were increased by taking only anticoagulant in addition to DAPT, but not by taking one anticoagulant and one antiplatelet agent.1928 Such further studies may improve the safety of oral anticoagulants.

Conclusion

Additional oral anticoagulant administration before flow diverter placement does not reduce the incidence of ischemic complications compared to two antiplatelet agents, but does increase the incidence of hemorrhagic complications, especially delayed aneurysm rupture. Furthermore, patients taking anticoagulants are unlikely to obtain complete obliteration of the cerebral aneurysm.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed consent

For this type of study, patient consent is not required.

Declaration of conflicting interests

The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: H.O. receives a donation in the form of a research fund to the endowed chair of his departments and about one million yen yearly from Medtronic Co., Ltd. The other authors have no conflicts of interest to declare.

Funding

The author(s) received no financial support for the research, authorship, and/or publication of this article.

ORCID iDs

Takashi Fujii https://orcid.org/0000-0002-2551-1144

Kenji Yatomi https://orcid.org/0000-0001-6325-898X

References

  • 1.Nelson PK, Lylyk P, Szikora I, et al. The pipeline embolization device for the intracranial treatment of aneurysms trial. AJNR Am J Neuroradiol 2011; 32: 34–40. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 2.Becske T, Kallmes DF, Saatci I, et al. Pipeline for uncoilable or failed aneurysms: results from a multicenter clinical trial. Radiology 2013; 267: 858–868. [DOI] [PubMed] [Google Scholar]
  • 3.Becske T, Potts MB, Shapiro M, et al. Pipeline for uncoilable or failed aneurysms: 3-year follow-up results. J Neurosurg 2017; 127: 81–88. [DOI] [PubMed] [Google Scholar]
  • 4.Oishi H, Teranishi K, Yatomi K, et al. Flow diverter therapy using a pipeline embolization device for 100 unruptured large and giant internal carotid artery aneurysms in a single center in a Japanese population. Neurol Med Chir (Tokyo) 2018; 58: 461–467. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 5.Gory B, Berge J, Bonafé A, et al. Flow diverters for intracranial aneurysms: the DIVERSION national prospective cohort study. Stroke 2019; 50: 3471–3480. [DOI] [PubMed] [Google Scholar]
  • 6.Brinjikji W, Murad MH, Lanzino G, et al. Endovascular treatment of intracranial aneurysms with flow diverters: a meta-analysis. Stroke 2013; 44: 442–447. [DOI] [PubMed] [Google Scholar]
  • 7.Rajah G, Narayanan S, Rangel-Castilla L. Update on flow diverters for the endovascular management of cerebral aneurysms. Neurosurg Focus 2017; 42: E2. [DOI] [PubMed] [Google Scholar]
  • 8.Hwang G, Kim JG, Song KS, et al. Delayed ischmic stroke after stent-assisted coil placement in crebral aneurym: characteristics and optimal duration of preventative dual antiplatelet therapy. Radiology 2014; 273: 194–201. [DOI] [PubMed] [Google Scholar]
  • 9.Yamada NK, Cross DT, 3rd, Pilgram TK, et al. Effect of antiplatelet therapy on thromboembolic complications of elective coil embolization of cerebral aneurysms. AJNR Am J Neuroradiol 2007; 28: 1778–1782. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 10.Chalouhi N, Jabbour P, Singhal S, et al. Stent-assisted coiling of intracranial aneurysms: predictors of complications, recanalization, and outcome in 508 cases. Stroke 2013; 44: 1348–1353. [DOI] [PubMed] [Google Scholar]
  • 11.Kang HS, Han MH, Kwon BJ, et al. Is clopidogrel premedication useful to reduce thromboembolic events during coil embolization for unruptured intracranial aneurysms? Neurosurgery 2010; 67: 1371–1376; discussion 1376. [DOI] [PubMed] [Google Scholar]
  • 12.Tarlov N, Norbash AM, Nguyen TN. The safety of anticoagulation in patients with intracranial aneurysms. J Neurointerv Surg 2013; 5: 405–409. [DOI] [PubMed] [Google Scholar]
  • 13.Pisters R, Lane DA, Nieuwlaat R, et al. A novel user-friendly score (HAS-BLED) to assess 1-year risk of major bleeding in patients with atrial fibrillation: the Euro Heart Survey. Chest 2010; 138: 1093–1100. [DOI] [PubMed] [Google Scholar]
  • 14.European Heart Rhythm Association, European Association for Cardio-Thoracic Surgery, Camm AJ, et al. Guidelines for the management of atrial fibrillation: the Task Force for the Management of Atrial Fibrillation of the European Society of Cardiology (ESC). Eur Heart J 2010; 31: 2369–2429. [DOI] [PubMed] [Google Scholar]
  • 15.Cruz JP, Chow M, O'Kelly C, et al. Delayed ipsilateral parenchymal hemorrhage following flow diversion for the treatment of anterior circulation aneurysms. AJNR Am J Neuroradiol 2012; 33: 603–608. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 16.Roy D, Milot G, Raymond J. Endovascular treatment of unruptured aneurysms. Stroke 2001; 32: 1998–2004. [DOI] [PubMed] [Google Scholar]
  • 17.Heeringa J, van der Kuip DA, Hofman A, et al. Prevalence, incidence and lifetime risk of atrial fibrillation: the Rotterdam study. Eur Heart J 2006; 27: 949–953. [DOI] [PubMed] [Google Scholar]
  • 18.Dobesh PP, Fanikos J. Direct oral anticoagulants for the prevention of stroke in patients with nonvalvular atrial fibrillation: understanding differences and similarities. Drugs 2015; 75: 1627–1644. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 19.Dewilde WJM, Oirbans T, Verheugt FWA, et al. ; WOEST study investigators. Use of clopidogrel with or without aspirin in patients taking oral anticoagulant therapy and undergoing percutaneous coronary intervention: an open-label, randomised, controlled trial. Lancet 2013; 381: 1107–1115. [DOI] [PubMed] [Google Scholar]
  • 20.Adeeb N, Moore JM, Wirtz M, et al. Predictors of incomplete occlusion following pipeline embolization of intracranial aneurysms: is it less effective in older patients? AJNR Am J Neuroradiol 2017; 38: 2295–2300. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 21.Ravindran K, DiStasio M, Laham R, et al. Histopathological demonstration of subacute endothelialization following aneurysm retreatment with the pipeline embolization device. World Neurosurg 2018; 118: 156–160. [DOI] [PubMed] [Google Scholar]
  • 22.Ding YH, Tieu T, Kallmes DF. Experimental testing of a new generation of flow diverters in sidewall aneurysms in rabbits. AJNR Am J Neuroradiol 2015; 36: 732–736. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 23.Ravindran K, Casabella AM, Cebral J, et al. Mechanism of action and biology of flow diverters in the treatment of intracranial aneurysms. Neurosurgery 2020; 86: S13–S19. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 24.Ravindran K, Salem MM, Alturki AY, et al. Endothelialization following flow diversion for intracranial aneurysms: a systematic review. AJNR Am J Neuroradiol 2019; 40: 295–301. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 25.Matsuda Y, Chung J, Lopes DK. Analysis of neointima development in flow diverters using optical coherence tomography imaging. J Neurointerv Surg 2018; 10: 162–167. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 26.Girdhar G, Andersen A, Pangerl E, et al. Thrombogenicity assessment of Pipeline Flex, Pipeline Shield, and FRED flow diverters in an in vitro human blood physiological flow loop model. J Biomed Mater Res A 2018; 106: 3195–3202. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 27.Oishi H, Teranishi K, Nonaka S, et al. Symptomatic very delayed parent artery occlusion after flow diversion stent embolization. Neurol Med Chir (Tokyo) 2016; 56: 350–353. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 28.Cannon CP, Bhatt DL, Oldgren J, et al. ; RE-DUAL PCI Steering Committee and Investigators. Dual antithrombotic therapy with Dabigatran after PCI in atrial fibrillation. N Engl J Med 2017; 377: 1513–1524. [DOI] [PubMed] [Google Scholar]
  • 29.Chow M, McDougall C, O'Kelly C, et al. Delayed spontaneous rupture of a posterior inferior cerebellar artery aneurysm following treatment with flow diversion: a clinicopathologic study. AJNR Am J Neuroradiol 2012; 33: E46–E51. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 30.Kulcsár Z, Houdart E, Bonafé A, et al. Intra-aneurysmal thrombosis as a possible cause of delayed aneurysm rupture after flow-diversion treatment. AJNR Am J Neuroradiol 2011; 32: 20–25. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 31.Hampton T, Walsh D, Tolias C, et al. Mural destabilization after aneurysm treatment with a flow-diverting device: a report of two cases. J Neurointerv Surg 2018; 10: i50–i55. [DOI] [PubMed] [Google Scholar]
  • 32.Turowski B, Macht S, Kulcsár Z, et al. Early fatal hemorrhage after endovascular cerebral aneurysm treatment with a flow diverter (SILK-Stent): do we need to rethink our concepts? Neuroradiology 2011; 53: 37–41. [DOI] [PubMed] [Google Scholar]
  • 33.Saatci I, Yavuz K, Ozer C, et al. Treatment of intracranial aneurysms using the pipeline flow-diverter embolization device: a single-center experience with long-term follow-up results. AJNR Am J Neuroradiol 2012; 33: 1436–1446. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 34.Oishi H, Teranishi K, Yatomi K, et al. Transvenous aneurysm sac and rupture point coil embolization of direct carotid cavernous fistula after pipeline embolization. NMC Case Rep J 2017; 5: 15–19. [DOI] [PMC free article] [PubMed] [Google Scholar]

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