Safety of tirofiban and dual antiplatelet therapy in treating intracranial aneurysms

BackgroundEndovascular treatment of intracranial aneurysms usually involves stent-assisted coiling (SAC) and flow diverters. Glycoprotein IIb/IIIa inhibitors such as tirofiban and dual antiplatelet therapy (DAPT) are required to prevent thromboembolic complications afterwards. We sought to determine the safety of tirofiban and DAPT in these cases.MethodsWe conducted a retrospective analysis of our database for patients with intracranial aneurysms who underwent SAC or flow diversion. The tirofiban-DAPT protocol used is described. Data regarding duration of infusion, placement of external ventricular devices (EVDs), complications, haemoglobin levels and platelet count before and 24 hours after antiplatelet therapy were collected and analysed.ResultsOne-hundred and forty-one patients with 148 aneurysms/procedures were included. 110 aneurysms were treated acutely and 38 electively. Minor and major haemorrhagic events were recognised in 20% (30/148) aneurysms. Only 5 (3.4%) intracerebral haemorrhages were symptomatic: 3 cortical/SAH and 2 EVD-related. The average blood volume in symptomatic haemorrhages was 24.8 cc versus 5.42 cc in asymptomatic haemorrhages (p=0.002). The rate of EVD-related haemorrhages was 15.7% (19/121) and only 2 (1.7%) were symptomatic. Most haemorrhagic events occurred in ruptured aneurysms (90.1%, p=0.01). No significant change in platelet count or haemoglobin levels before and 24 hours after administration of tirofiban and DAPT was documented. Concomitant administration of heparin did not increase haemorrhagic events.ConclusionThe use of the GP IIb/IIIa inhibitors tirofiban and DAPT in this series was safe. Tirofiban and DAPT did not affect platelet count or haemoglobin levels and did not increase rate of symptomatic haemorrhages or thromboembolic complications.

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Antiplatelet Therapy in Flow Diversion

Neurosurgery ◽

10.1093/neuros/nyz391 ◽

2019 ◽

Vol 86 (Supplement_1) ◽

pp. S47-S52 ◽

Cited By ~ 7

Author(s):

Daniel A Tonetti ◽

Brian T Jankowitz ◽

Bradley A Gross

Keyword(s):

Antiplatelet Therapy ◽

Dual Antiplatelet Therapy ◽

Response Assessment ◽

Similar Efficacy ◽

Subsequent Treatment ◽

Flow Diversion ◽

Thromboembolic Complications ◽

Ruptured Aneurysms ◽

Thrombotic Complications ◽

Flow Diverters

Abstract Dual antiplatelet therapy is typically employed as a means to mitigate thromboembolic complications after deployment of flow diverters, most commonly consisting of aspirin with either clopidogrel, prasugrel, or ticagrelor. Recent studies have demonstrated at least similar efficacy for ticagrelor as compared to clopidogrel in the form of periprocedural complications and angiographic results. Though controversial, systematic reviews of platelet function assay usage have demonstrated greater rates of thrombotic complications in antiplatelet hyporesponders and greater rates of hemorrhagic complications in hyperresponders. Though in its infancy, the management of antiplatelet therapy for acutely ruptured aneurysms treated with flow diversion is not yet standardized, with approaches including intravenous glycoprotein IIb-IIIa inhibitors and subsequent antiplatelet loading vs antiplatelet loading, response assessment, and subsequent treatment.

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Safety and efficacy of a new prophylactic tirofiban protocol without oral intraoperative antiplatelet therapy for endovascular treatment of ruptured intracranial aneurysms

Journal of NeuroInterventional Surgery ◽

10.1136/neurintsurg-2015-012055 ◽

2015 ◽

Vol 8 (11) ◽

pp. 1148-1153 ◽

Cited By ~ 14

Author(s):

Xiao-dong Liang ◽

Zi-liang Wang ◽

Tian-xiao Li ◽

Ying-kun He ◽

Wei-xing Bai ◽

...

Keyword(s):

Endovascular Treatment ◽

Antiplatelet Therapy ◽

Intracranial Hemorrhage ◽

Intracranial Aneurysms ◽

Dual Antiplatelet Therapy ◽

Thromboembolic Events ◽

Maintenance Infusion ◽

Safety And Efficacy ◽

Fatal Hemorrhage ◽

Ruptured Intracranial Aneurysms

BackgroundCoil embolization of intracranial aneurysms is being increasingly used; however, thromboembolic events have become a major periprocedural complication.ObjectiveTo determine the safety and efficacy of prophylactic tirofiban in patients with ruptured intracranial aneurysms.MethodsTirofiban was administered as an intravenous bolus (8.0 μg/kg over 3 min) followed by a maintenance infusion (0.10 μg/kg/min) before stent deployment or after completion of single coiling. Dual oral antiplatelet therapy (loading doses) was overlapped with half the tirofiban dose 2 h before cessation of the tirofiban infusion. Cases of intracranial hemorrhage or thromboembolism were recorded.ResultsTirofiban was prophylactically used in 221 patients, including 175 (79.19%) who underwent stent-assisted coiling and 46 (20.81%) who underwent single coiling, all in the setting of aneurysmal subarachnoid hemorrhage. Six (2.71%) cases of intracranial hemorrhage occurred, including four (1.81%) tirofiban-related cases and two (0.90%) antiplatelet therapy-related cases. There were two (0.90%) cases of fatal hemorrhage, one related to tirofiban and the other related to dual antiplatelet therapy. Thromboembolic events occurred in seven (3.17%) patients (6 stent-assisted embolization, 1 single coiling), of which one (0.45%) event occurred during stenting and six (2.72%) occurred during intravenous tirofiban maintenance. No thromboembolic events related to dual antiplatelet therapy were found.ConclusionsTirofiban bolus over 3 min followed by maintenance infusion appears to be a safe and efficient prophylactic protocol for the endovascular treatment of ruptured intracranial aneurysms and may be an alternative to intraoperative oral antiplatelet therapy, especially in the case of stent-assisted embolization.

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Reduction of thromboembolic complications during the endovascular treatment of unruptured aneurysms by employing a tailored dual antiplatelet regimen using aspirin and prasugrel

Journal of NeuroInterventional Surgery ◽

10.1136/neurintsurg-2020-016994 ◽

2021 ◽

pp. neurintsurg-2020-016994

Author(s):

Saeko Higashiguchi ◽

Akiyo Sadato ◽

Ichiro Nakahara ◽

Shoji Matsumoto ◽

Motoharu Hayakawa ◽

...

Keyword(s):

Endovascular Treatment ◽

Antiplatelet Therapy ◽

Dual Antiplatelet Therapy ◽

Cerebral Aneurysms ◽

Poor Response ◽

Perioperative Period ◽

Thromboembolic Complications ◽

Unruptured Aneurysms ◽

Verifynow Assay ◽

Unruptured Cerebral Aneurysms

BackgroundThromboembolic complications (TECs) are frequent during the endovascular treatment of unruptured aneurysms. To prevent TECs, dual antiplatelet therapy using aspirin and clopidogrel is recommended for the perioperative period. In patients with a poor response, clopidogrel is a risk factor for TECs. To prevent TECs, our study assessed the stratified use of prasugrel.MethodsPatients who underwent endovascular therapy for unruptured cerebral aneurysms from April 2017 to August 2019 were enrolled in this clinical study and given premedication with aspirin and clopidogrel for 2 weeks prior to the procedure. P2Y12 reaction units (PRU) were measured using the VerifyNow assay on the day before the procedure (tailored group). In subgroups with PRU <240, the clopidogrel dose was maintained (CPG subgroup). In subgroups with PRU ≥240, clopidogrel was changed to prasugrel (PSG subgroup). We compared the occurrence of TECs with retrospective consecutive cases from January 2015 to March 2017 without PRU assessments (non-tailored group). The frequency of TECs within 30 days was assessed as the primary endpoint.ResultsThe tailored and non-tailored groups comprised 167 and 50 patients, respectively. TECs occurred in 11 (6.6%) and 8 (16%) patients in the tailored and non-tailored groups (P=0.048), respectively. The HR for TECs was significantly reduced in the tailored group (HR 0.3, 95% CI 0.11 to 0.81); P=0.017) compared with the non-tailored group.ConclusionThe results suggest that tailored dual antiplatelet therapy medication with PRU significantly reduces the frequency of TECs without increasing hemorrhagic complications.

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Anticoagulation in addition to dual antiplatelet therapy has no impact on long-term follow-up after endovascular treatment of (sub)acute lower limb ischemia

VASA ◽

10.1024/0301-1526/a000786 ◽

2019 ◽

Vol 48 (4) ◽

pp. 321-329

Author(s):

Mariya Kronlage ◽

Erwin Blessing ◽

Oliver J. Müller ◽

Britta Heilmeier ◽

Hugo A. Katus ◽

...

Keyword(s):

Endovascular Treatment ◽

Antiplatelet Therapy ◽

Dual Antiplatelet Therapy ◽

Limb Ischemia ◽

Bleeding Complications ◽

Severe Bleeding ◽

Short Term ◽

Long Term Follow Up

Summary. Background: To assess the impact of short- vs. long-term anticoagulation in addition to standard dual antiplatelet therapy (DAPT) upon endovascular treatment of (sub)acute thrombembolic occlusions of the lower extremity. Patient and methods: Retrospective analysis was conducted on 202 patients with a thrombembolic occlusion of lower extremities, followed by crirical limb ischemia that received endovascular treatment including thrombolysis, mechanical thrombectomy, or a combination of both between 2006 and 2015 at a single center. Following antithrombotic regimes were compared: 1) dual antiplatelet therapy, DAPT for 4 weeks (aspirin 100 mg/d and clopidogrel 75 mg/d) upon intervention, followed by a lifelong single antiplatelet therapy; 2) DAPT plus short term anticoagulation for 4 weeks, followed by a lifelong single antiplatelet therapy; 3) DAPT plus long term anticoagulation for > 4 weeks, followed by a lifelong anticoagulation. Results: Endovascular treatment was associated with high immediate revascularization (> 98 %), as well as overall and amputation-free survival rates (> 85 %), independent from the chosen anticoagulation regime in a two-year follow up, p > 0.05. Anticoagulation in addition to standard antiplatelet therapy had no significant effect on patency or freedom from target lesion revascularization (TLR) 24 months upon index procedure for both thrombotic and embolic occlusions. Severe bleeding complications occurred more often in the long-term anticoagulation group (9.3 % vs. 5.6 % (short-term group) and 6.5 % (DAPT group), p > 0.05). Conclusions: Our observational study demonstrates that the choice of an antithrombotic regime had no impact on the long-term follow-up after endovascular treatment of acute thrombembolic limb ischemia whereas prolonged anticoagulation was associated with a nominal increase in severe bleeding complications.

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Safety and efficacy of ticagrelor as single antiplatelet therapy in prevention of thromboembolic complications associated with the Pipeline Embolization Device (PED): multicenter experience

Journal of NeuroInterventional Surgery ◽

10.1136/neurintsurg-2020-015978 ◽

2020 ◽

Vol 12 (11) ◽

pp. 1113-1116 ◽

Cited By ~ 1

Author(s):

Mahmoud H Mohammaden ◽

Stephen W English ◽

Christopher J Stapleton ◽

Eman Khedr ◽

Ahmed Shoyb ◽

...

Keyword(s):

Antiplatelet Therapy ◽

Intracranial Aneurysms ◽

Posterior Circulation ◽

Thromboembolic Complications ◽

Anterior Circulation ◽

Safety And Efficacy ◽

Complex Aneurysm ◽

Post Procedure ◽

Systemic Side Effects ◽

Ischemic Events

BackgroundFlow diversion (FD) is a common treatment modality for complex intracranial aneurysms. A major concern regarding the use of FD is thromboembolic events (TEE). There is debate surrounding the optimal antiplatelet regimen to prevent TEE. We aim to evaluate the safety and efficacy of ticagrelor as a single antiplatelet therapy (SAPT) for the prevention of TEE following FD for complex aneurysm treatment.MethodsA retrospective review of a prospectively maintained neuroendovascular database at three endovascular centers was performed. Patients were included if they had an intracranial aneurysm that was treated with FD between January 2018 and September 2019 and were treated with ticagrelor as SAPT. Primary outcomes included early (within 72 hours post-procedure) and late (within 6 months) ischemic events.ResultsA total of 24 patients (mean age 47.7 years) with 36 aneurysms were eligible for analysis, including 15 (62.5%) females. 14 (58.3%) patients presented with subarachnoid hemorrhage. 35 aneurysms arose from the anterior circulation and 1 from the posterior circulation. 23 aneurysms had a saccular morphology, whereas 7 were fusiform and 6 were blister. For the treatment of all 36 aneurysms, 30 procedures were performed with 32 FD devices. Procedural in-stent thrombosis occurred in 2 cases and was treated with intra-arterial tirofiban without complications. Aneurysm re-bleeding was reported in 1 (4.2%) patient. There were no reported early or late TEE. Three patients discontinued ticagrelor due to systemic side effects.ConclusionTicagrelor is a safe and effective SAPT for the prevention of TEE after FD. Large multicenter prospective studies are warranted to validate our findings.

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Long-Term Follow-up Study of Endovascularly Treated Intracranial Aneurysms

Interventional Neuroradiology ◽

10.1177/159101991001600301 ◽

2010 ◽

Vol 16 (3) ◽

pp. 231-239 ◽

Cited By ~ 5

Author(s):

L.M. Pyysalo ◽

L.H. Keski-Nisula ◽

T.T. Niskakangas ◽

V.J. Kähärä ◽

J.E. Öhman

Keyword(s):

Endovascular Treatment ◽

Intracranial Aneurysms ◽

Bleeding Rate ◽

Unruptured Aneurysms ◽

Ruptured Aneurysms ◽

Follow Up Study ◽

Long Term Follow Up ◽

Rebleeding Rate

Long-term follow-up studies after endovascular treatment for intracranial aneurysm are still rare and inconclusive. The aim of this study was to assess the long-term clinical and angiographic outcome of patients with endovascularly treated aneurysms. The clinical outcome of all 185 patients with endovascularly treated aneurysms were analyzed and 77 out of 122 surviving patients were examined with MRI and MRA nine to 16 years (mean 11 years) after the initial endovascular treatment. Sixty-three patients were deceased at the time of follow-up. The cause of death was aneurysm-related in 34 (54%) patients. The annual rebleeding rate from the treated aneurysms was 1.3% in the ruptured group and 0.1% in the unruptured group. In long-term follow-up MRA 18 aneurysms (53%) were graded as complete, 11 aneurysms (32%) had neck remnants and five aneurysms (15%) were incompletely occluded in the ruptured group. The occlusion grade was lower in the unruptured group with 20 aneurysms (41%) graded as complete, 11 (22%) had neck remnants and 18 (37%) were incomplete. However, only three aneurysms were unstable during the follow-up period and needed retreatment. Endovascular treatment of unruptured aneurysms showed incomplete angiographic outcome in 37% of cases. However, the annual bleeding rate was as low as 0.1%. Endovascular treatment of ruptured aneurysms showed incomplete angiographic outcome in 15% of cases and the annual rebleeding rate was 1,3%.

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

Journal of Neurosurgery ◽

10.3171/2016.9.jns161340 ◽

2017 ◽

Vol 127 (6) ◽

pp. 1326-1332 ◽

Cited By ~ 18

Author(s):

Nancy J. Edwards ◽

Wesley H. Jones ◽

Aditya Sanzgiri ◽

Juan Corona ◽

Mark Dannenbaum ◽

...

Keyword(s):

High Risk ◽

Antiplatelet Therapy ◽

Intracranial Aneurysms ◽

Treated Group ◽

Parent Artery ◽

Aneurysm Neck ◽

High Risk Patients ◽

Ruptured Aneurysms ◽

Hemorrhagic Complications ◽

Risk Patients

OBJECTIVEThe 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.METHODSThe 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.RESULTSSix 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).CONCLUSIONSThe 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.

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Problems with Antiplatelet Therapy in Children with Cyanotic Heart Disease

10.1055/s-0039-1680828 ◽

1977 ◽

Author(s):

A.H. Sutor ◽

B. Schmidt ◽

H.P. Lorenz ◽

J. Vogt

Keyword(s):

Platelet Count ◽

Heart Disease ◽

Antiplatelet Therapy ◽

Bleeding Time ◽

Fibrinolytic Therapy ◽

Antiplatelet Drugs ◽

Cyanotic Heart Disease ◽

Consumption Coagulopathy ◽

Thromboembolic Complications ◽

Cardiac Decompensation

Children with cyanotic heart disease are endangered by thromboembolic complications. However, in our 17 patients we could not find laboratory evidence for consumption coagulopathy but found evidence for isolated platelet consumption with increased platelet turnover. We therefore applied antiplatelet drugs (acetylsalicylic acid and dipyridamol) in order to prevent thromboembolic complications. With antiplatelet therapy the platelet count increased in average, however, 12 of 17 children with cyanotic heart disease did not show prolongation of the bleeding time as did controls. There is strong evidence that in these children an adequate blood-level of antiplatelet drugs was not obtained either by non-absorption (due to cardiac decompensation) or because of relative underdosage (due to increased platelet turnover) of the antiplatelet drugs. 2 of these patients who had a normal bleeding time, inspite of antiplatelet drugs, suffered from thromboembolic complications requiring fibrinolytic therapy. As a concequence we increase the dosage of antiplatelet drugs when the bleeding time does not prolong.

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Multiple Intracranial Aneurysms

Interventional Neuroradiology ◽

10.1177/159101990200800201 ◽

2002 ◽

Vol 8 (2) ◽

pp. 95-106 ◽

Cited By ~ 4

Author(s):

F. Mont'Alverne ◽

A. Tournade ◽

C. Riquelme ◽

M. Musacchio

Keyword(s):

Endovascular Treatment ◽

Intracranial Aneurysms ◽

Arterial Wall ◽

Multiple Intracranial Aneurysms ◽

Ruptured Aneurysms ◽

Mixed Treatment ◽

Lost To Follow Up ◽

High Degree ◽

Mean Time

We evaluate endovascular treatment (EVT) as an option to deal with multiple intracranial aneurysms(MA). From 1994 to 2001, 24 patients underwent EVT for 59 MA. Patients were followed-up clinically and angiographically in a period ranging from 6 to 93 months (mean time of 22.2) and from 4 to 69 months (mean time of 19.3), respectively. Ten patients (41.6%) were treated either by EVT (n=7, 29, 16%) or by mixed treatment (EVT and surgery; n=3, 12.5%). Reasons for treating just ruptured aneurysms: six (25%) had aneurysms smaller than 5 mm; three (12.5%) deaths; two (8.33%) were in the subacute period; two (8.33%) lost to follow-up; one (4.17%) authorised no procedure. No rebleeding was detected at the clinical follow-up, but there were five deaths. At immediate arteriographic control: 28 (85%) aneurysms were fully occluded, four (12%) with neck flow and one (03%) with sac flow. For 20 aneurysms followed-up: stability of occlusion was reached in seven cases (35%) and repermeabilization in 13 (65%). Management of recanalization was close arteriography in seven (54%), re-embolization in five (38%) and surgery in one (08%). When treating MA, EVT is advisable either alone or in mixed therapy. As a high degree of repermeabilization was disclosed, strict arteriographic control is required. The mechanisms underlying aneurysmal formation may be also involved in the recanalization phenomenon, a possible new manifestation of the fragility of the arterial wall.

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Endovascular Treatment of Intracranial Aneurysms in the Elderly: Single-Center Experience in 63 Consecutive Patients

Neurosurgery ◽

10.1227/01.neu.0000185583.25420.df ◽

2005 ◽

Vol 57 (6) ◽

pp. 1096-1102 ◽

Cited By ~ 71

Author(s):

YiLing Cai ◽

Laurent Spelle ◽

Huan Wang ◽

Michel Piotin ◽

Charbel Mounayer ◽

...

Keyword(s):

Subarachnoid Hemorrhage ◽

Endovascular Treatment ◽

Intracranial Aneurysms ◽

Endovascular Procedures ◽

The Elderly ◽

High Grade ◽

Single Center ◽

Unruptured Aneurysms ◽

Ruptured Aneurysms

Abstract OBJECTIVE: With a globally aging population, it is imperative to develop specific treatment strategies for intracranial aneurysms in the elderly. However, the optimal management of intracranial aneurysms in the elderly remains controversial, particularly for the unruptured aneurysms. Although endovascular treatment is increasingly being used for the management of aneurysms, large endovascular series in the elderly population are relatively lacking, especially with regard to the unruptured aneurysms. We present our single-center endovascular experience in treating intracranial aneurysms in 63 consecutive patients 70 years of age and older. METHODS: Between November 1998 and December 2003, among a total of 990 patients with intracranial aneurysms treated endovascularly at our center, 63 patients (6%) were 70 years of age or older. Forty-one patients presented with subarachnoid hemorrhage (SAH), and 22 presented with symptomatic unruptured aneurysms. A total of 84 aneurysms were detected in these 63 patients. Only those responsible for either the subarachnoid hemorrhage or clinical symptoms (68 aneurysms) were treated. The aneurysm characteristics, endovascular procedures and techniques, angiographic and clinical outcomes, and complications were reviewed. RESULTS: Selective embolization failed in three aneurysms (4%). In the remaining 65 aneurysms, complete occlusion was achieved in 33 aneurysms (51%), neck remnant was observed in 17 aneurysms (27%), and residual aneurysmal filling was observed in six aneurysms (9%). Parent vessel occlusion was used in the treatment of nine aneurysms (13%). Thirteen procedure-related complications occurred (19%), six of which resulted in clinical complications (9%). Nine deaths (14%) occurred; three (5%) were directly related to the endovascular procedures, and six (9%) were related to the medical complications of SAH. The remaining 54 patients had a mean clinical follow-up time of 13 months (range, 1–47 mo). Ninety-one percent (20 out of 22) of the patients with unruptured aneurysms and 89% (25/28) of the patients with low-grade (Hunt and Hess Grade I and II) ruptured aneurysms achieved excellent outcomes (modified Rankin Scale score, 0–1), whereas 77% (10 out of 13) of the patients with high-grade (Hunt and Hess Grade ≥ III) ruptured aneurysms either died or had very poor outcomes (modified Rankin Scale score, 4–5). Angiographic follow-up (mean, 11 mo; range, 3–38 mo) was obtained in 34 of the 54 living patients (63%). Two aneurysms demonstrated minor changes that required no further treatment (5%). Five aneurysms showed major recurrences (17%), all of which were successfully retreated endovascularly. CONCLUSION: The elderly patients should merit strong consideration for endovascular treatment of both ruptured and symptomatic unruptured intracranial aneurysms. However, in elderly patients with high-grade subarachnoid hemorrhage, morbidity and mortality rates remain high.

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