ticagrelor and Intracranial-Aneurysm

The aim of this review is to provide an overview of the use of antiplatelet medication in neurointervention, with a focus on the clinical indications for antiplatelet use in both preventing and reducing platelet aggregation. This review will cover current antiplatelet medications, pharmacokinetics, and pharmacodynamics. We will provide an overview of different endovascular devices and discuss the antiplatelet regimes in neurointervention, highlighting gaps in evidence and scope for future studies.Two randomized controlled trials have evaluated antiplatelet use in the setting of acute large vessel occlusion stroke, with neither demonstrating benefit in their overall cohorts. Evidence on antiplatelet medication for both acute and elective stenting for acute stroke and treatment of cerebral aneurysms is currently based on large case series, and practice in neurointervention has increasingly utilized dual antiplatelet regimes with clopidogrel and second-line agents like prasugrel and ticagrelor. Clopidogrel function testing has an increasing role in neurointerventional procedures, particularly for high metal surface area stents such as the braided flow diverter type stents. Intravenous glycoprotein IIB/IIIA inhibitors have been utilized for both acute bridging and rescue therapy.Antiplatelet decision making is complex, and there are few randomized control trials to guide clinical practice. Comparative trials to guide decision making remain important in both the acute and elective settings. Standardised protocols incorporating platelet function testing may play a role in assisting decision making until more robust clinical evidence is available, particularly in the context of acute neurointerventional stenting for stroke and ruptured cerebral aneurysms.

Topics: Clopidogrel; Humans; Intracranial Aneurysm; Platelet Aggregation Inhibitors; Stroke; Ticagrelor; Treatment Outcome

Dual antiplatelet therapy (DAPT) of aspirin plus clopidogrel is commonly used in patients with unruptured intracranial aneurysms treated with stent-assisted coil (SAC) embolization. However, the unpredictable clopidogrel efficacy of the 5%-55% nonresponders limits its use. Ticagrelor, as a potential alternative of clopidogrel, is an antiplatelet agent with low resistance rates but uncertain efficacy and safety in these patients.. A single-center cohort study was performed to compare the efficacy and safety of ticagrelor with clopidogrel in the DAPT regimen in patients with unruptured intracranial aneurysms and treated with SAC. The patients with clopidogrel resistance identified as inadequate adenosine diphosphate inhibition rate determined by thromboelastography were treated with ticagrelor instead, and both drugs achieved adequate suppression of platelet aggregation when stents were implanted. The occurrence of major adverse cardiovascular and cerebrovascular events (MACCE) and bleeding events was recorded through 6 months follow-up.. Data from 86 patients with 99 unruptured intracranial aneurysms and treated by SAC with clopidogrel were compared with those from 108 patients with 111 aneurysms and treated with ticagrelor. Neither the baseline characteristics nor the incidence of the MACCE or bleeding events differed between the groups. Ticagrelor exerted significantly higher adenosine diphosphate inhibition rate than that of the clopidogrel. Multivariable logistic regression analysis showed that the incidence of MACCE was related to hematocrit and fibrinogen levels.. Ticagrelor seemed to be as effective and safe as clopidogrel for SAC in unruptured intracranial aneurysms. Hematocrit and fibrinogen levels were independent risk factors for the incidence of MACCE.

Topics: Adenosine Diphosphate; Clopidogrel; Cohort Studies; Embolization, Therapeutic; Fibrinogen; Humans; Intracranial Aneurysm; Platelet Aggregation Inhibitors; Stents; Ticagrelor; Treatment Outcome

Antiplatelet therapy (APT) is a key element limiting the risk of thromboembolic events (TEE) in neuroendovascular procedures, including aneurysm treatment with flowdiverter. Clopidogrel combined with aspirin is the mostly reported dual APT (DAPT). However, resistance phenomenon and intraindividual efficacy fluctuation are identified limitations. In recent years, ticagrelor has been increasingly used in this indication. We compared these two DAPT regimens for intracranial aneurysm treated with flowdiverter.. We conducted a multicentric retrospective study from prospectively maintained databases in two high volume centers extracting consecutive patients presenting unruptured intracranial aneurysm treated with flowdiverter and receiving DAPT (May 2015 to December 2019).  Two groups were compared according to their DAPT regimen: "ticagrelor+aspirin" and "clopidogrel+aspirin". Clopidogrel group was systematically checked with platelet test inhibition before endovascular procedure. The primary endpoint was composite, defined as any thrombo-embolic event (TEE) or major hemorrhagic event occurring the first 6 months during and after embolization RESULTS: 260 patients met our inclusion criteria. Baseline patients and aneurysms characteristics were comparable between groups, except for aneurysm location, median size and pre-treatment modified Rankin scale. No significant difference was observed regarding the primary composite outcome: 11.5% (12/104) in the ticagrelor group versus 10.9% (17/156) in the clopidogrel group (p = 1.000). There was also no significant difference in secondary outcomes including TEE (10.5 vs 9.0%; p = 0.673), major hemorrhage (0.9 vs 1.2%; p = 0.651) and clinical outcome (at least 1-point mRS worsening during follow up: 6.7% vs 8.3%; p = 0.813).. First-line DAPT with ticagrelor+aspirin seems as safe and effective as clopidogrel+aspirin regimen.

Topics: Aspirin; Clopidogrel; Hemorrhage; Humans; Intracranial Aneurysm; Platelet Aggregation Inhibitors; Retrospective Studies; Thromboembolism; Ticagrelor; Treatment Outcome

Nuisance bleeding (NB) without urgent medical attention is rarely characterized despite its frequent occurrence in patients with cerebral aneurysms undergoing flow diversion (FD) who are maintained on dual antiplatelet therapy (DAPT). This study explored the risk factors for NB. Patients with unruptured cerebral aneurysms who underwent intervention using FD (July 2018 to May 2022) and had follow-up data were enrolled. Patient demographics, clinical characteristics, aneurysm features and follow-up data were analysed. Bleeding complications were classified as NB, internal bleeding and alarming bleeding. NB was characterized by easy bruising, bleeding from small cuts and nonfatal petechiae and ecchymosis. Univariate and multivariate logistic regression analyses were performed to determine risk factors for NB. This study assessed 121 patients. Of these, 52 (43.0%) patients had NB. Compared with the non-bleeding group, the NB group had more females (82.7% vs. 56.5%; p = 0.003), lower smoking rate (7.7% vs. 23.2%; p = 0.027) and smaller aneurysms (6.65 mm [4.60-9.60 mm] vs. 8.82 mm [5.65-15.65 mm]; p = 0.007) and had more patients maintained on ticagrelor-containing DAPT regimen (90.4% vs. 66.7%; p = 0.002). Multivariate logistic regression revealed that ticagrelor-containing DAPT regimen (odds ratio, 3.91; 95% confidence interval, 1.29-11.87; p = 0.016) was associated with NB. These results suggest that NB is a common bleeding complaint in patients on DAPT. In patients undergoing FD, DAPT with ticagrelor was the only independent risk factor for NB.

Topics: Female; Hemorrhage; Humans; Intracranial Aneurysm; Platelet Aggregation Inhibitors; Risk Factors; Ticagrelor; Treatment Outcome

Dual antiplatelet therapy is widely used for stent-assisted coil embolization (SACE) for unruptured intracranial aneurysms (UIAs) to prevent thromboembolic events (TEs). Compared to clopidogrel associated with aspirin, knowledge of the safety and efficacy of ticagrelor is lacking in large studies to date.. A retrospective cohort study was conducted from January 2016 to December 2018 with at least one year of follow-up in a single institution and systemic review.. Altogether, 153 patients with UIA receiving SACE were separated into two groups: 113 patients receiving clopidogrel plus aspirin and 40 patients receiving ticagrelor plus aspirin. Acute in-stent thrombotic events were noted in two patients in the clopidogrel group (1.77%) and none in the ticagrelor group (0%). Additionally, one patient (0.88%) in the clopidogrel group had an early ischemic stroke (<3 months). Delayed ischemic stroke was noted in 6 patients (5.31%) in the clopidogrel group and 3 patients (7.50%) in the ticagrelor group. There were no major hemorrhagic events in either group. The two groups showed no significant differences with regard to ischemic stroke or hemorrhagic stroke.. Compared to the clopidogrel based regimen, ticagrelor can also reduce TEs without increasing bleeding tendency for SACE of UIAs. Ticagrelor combined with low-dose aspirin is a safe and effective alternative option for SACE.

Topics: Aspirin; Clopidogrel; Embolization, Therapeutic; Humans; Intracranial Aneurysm; Platelet Aggregation Inhibitors; Retrospective Studies; Stents; Thromboembolism; Ticagrelor; Treatment Outcome

Ticagrelor is a novel P2Y12 antagonist, and little is known about its efficacy and safety in the endovascular treatment of aneurysms. This study evaluated the efficacy and safety of ticagrelor versus clopidogrel for stent-assisted coiling or flow-diversion treatment in patients with unruptured cerebral aneurysms.. From November 2003 to February 2019, two hundred one patients (mean age, 57.5 years; 156 women) with 233 unruptured aneurysms underwent stent-assisted coiling or flow-diversion treatment. All patients received antiplatelet therapy of aspirin plus clopidogrel (clopidogrel group, 121 patients with 140 aneurysms) or aspirin plus ticagrelor (ticagrelor group, 80 patients with 93 aneurysms). The clinical and radiologic data in each group were retrospectively reviewed and compared.. Ticagrelor appears to be as effective and safe as clopidogrel in stent-assisted coiling or flow-diversion treatment for unruptured cerebral aneurysms.

Topics: Clopidogrel; Dual Anti-Platelet Therapy; Embolization, Therapeutic; Female; Humans; Intracranial Aneurysm; Male; Middle Aged; Platelet Aggregation Inhibitors; Retrospective Studies; Stents; Ticagrelor; Treatment Outcome

Flow 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.. A 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.. A 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.. Ticagrelor is a safe and effective SAPT for the prevention of TEE after FD. Large multicenter prospective studies are warranted to validate our findings.

Topics: Adult; Aged; Embolization, Therapeutic; Female; Follow-Up Studies; Humans; Intracranial Aneurysm; Male; Middle Aged; Platelet Aggregation Inhibitors; Prospective Studies; Retrospective Studies; Thromboembolism; Ticagrelor; Treatment Outcome

Dual antiplatelet therapy consisting of aspirin and clopidogrel is the standard of care for neurointerventional stenting and flow diversion. Platelet function testing has been increasingly performed to identify patients with a hypo- or hyper-response to clopidogrel. Ticagrelor has been a popular alternative antiplatelet agent for such patients. We assessed the role of platelet function testing in patients receiving ticagrelor and undergoing stenting or flow diversion.. The data from patients who had undergone stent-assisted coiling or Pipeline flow diversion of a cerebral aneurysm with ticagrelor therapy at any point during their treatment course from May 2017 to August 2019 at a single academic institution in the United States were retrospectively reviewed. Platelet function testing was used to determine the P2Y. A total of 28 patients with 29 aneurysms were treated while receiving ticagrelor. Of the 29 aneurysms, 16 (55.2%) were treated with flow diversion and 13 (44.8%) with stent-assisted coiling. Four thromboembolic complications (13.8%) and no hemorrhagic complications developed. Of the 8 patients with ≥1 PRU value >100, 4 (50%) had experienced a thromboembolic complication. The patients without a PRU value >100 did not experience any complications.. A risk of thromboembolic complications exists for patients receiving ticagrelor, which correlated with the PRUs in the present preliminary study. The findings from the present study suggest that the safe PRU range for patients receiving ticagrelor should be shifted to 0-100, which is lower than that of clopidogrel, thought to be 60-210. Further validation of the optimal PRU range for patients receiving ticagrelor is necessary.

Topics: Adult; Aged; Aged, 80 and over; Cohort Studies; Female; Follow-Up Studies; Humans; Intracranial Aneurysm; Male; Middle Aged; Purinergic P2Y Receptor Antagonists; Receptors, Purinergic P2Y12; Retrospective Studies; Self Expandable Metallic Stents; Ticagrelor

To reduce procedural thromboembolisms, tailored antiplatelet drug preparation has been used according to antiplatelet resistance for endovascular coiling of unruptured aneurysms. We compared an aspirin plus clopidogrel group with a ticagrelor group using diffusion-weighted imaging (DWI) after stent-assisted coiling for unruptured aneurysms.. From October 2018 to April 2019, 72 patients with 78 aneurysms underwent stent-assisted coiling, with aspirin plus clopidogrel (n = 20 patients with 22 aneurysms) or ticagrelor (n = 52 patients with 56 aneurysms) as an antiplatelet preparation, and were enrolled in our study. All patients were evaluated using DWI 2 h after coiling to detect procedural thromboembolisms.. Postprocedure infarction was observed on DWI in 37 procedures (47.4%), and symptomatic infarction occurred in 1 procedure (1.28%). Postprocedure infarction was significantly lower in the aspirin plus clopidogrel than in ticagrelor group (27.3% vs. 55.4%, p = 0.043). Postprocedure infarction was associated with aneurysm type (sidewall aneurysm (30.8%) vs. aneurysm with incorporated branches (64.1%), p = 0.006) and guiding catheter type (single (23.8%) vs. double (56.1%), p = 0.020). Multivariable logistic regression analysis demonstrated that postprocedure infarction was related to aneurysm type (adjusted odds ratio (OR); 3.317, confidence interval (CI); 1.223-8.991, p = 0.018), guiding catheter type (adjusted OR; 2.783, CI; 0.828-9.353, p = 0.098), and antiplatelet medication (adjusted OR; 1.295, CI; 0.969-1.730, p = 0.080).. Postprocedure infarction was observed on DWI after stent-assisted coiling for unruptured aneurysms more frequently in the ticagrelor group than in the aspirin plus clopidogrel group. However, our study suggests that postprocedure infarction is more associated with aneurysm type than antiplatelet medication.

Topics: Adult; Aged; Aspirin; Clopidogrel; Diffusion Magnetic Resonance Imaging; Embolization, Therapeutic; Female; Humans; Intracranial Aneurysm; Male; Middle Aged; Platelet Aggregation Inhibitors; Stents; Thromboembolism; Ticagrelor

Dual antiplatelet therapy (DAPT) associating aspirin + clopidogrel is commonly utilized in neurovascular interventions despite unpredictable clopidogrel efficacy with 4% to 50% of patients considered nonresponders. Ticagrelor is an antiplatelet agent with low resistance rates but unknown efficacy and safety in neurovascular patients.. To evaluate frequency of ischemic and hemorrhagic events in patients treated with aspirin and ticagrelor when associated with perioperative heparin bolus for unruptured aneurysms treated with intracranial stents.. One hundred fifty-four consecutive patients with unruptured intracranial aneurysms treated by stent procedures (113 = flow diverter stent [FDS], 41 = stent-assisted coiling) were retrospectively analyzed. All patients received aspirin and ticagrelor without platelet function testing. Patients were separated in 2 groups following perioperative heparin dose: group I = 70 U/kg; group II = 50 U/kg. FDS versus stent-assisted coiling procedures were also separately analyzed.. Nine patients (5.8%) presented symptomatic neurological complications poststenting (3 ischemic, 6 hemorrhagic): 8 patients received 70 U/kg of heparin (11.1%) and 1 patient received 50 U/kg (1.2%; P < .009). Four patients died (2.6%) during the 3-mo follow-up period-all deaths were correlated to intracranial hemorrhage: 3 at group I and 1 at group II (P < .251). No difference in complications or death was observed considering separately FDS and stent-assisted coiling procedures.. This study did not find more neurological complications than in previous neurointerventional reports using DAPT with aspirin + ticagrelor or aspirin + clopidogrel. Overall number of neurological complications was lower when a lower dose of heparin was administered. Neurovascular studies comparing clopidogrel to ticagrelor and different doses of heparin are necessary to demonstrate which association is more efficient with lower complication rates.

Topics: Aspirin; Dual Anti-Platelet Therapy; Humans; Intracranial Aneurysm; Platelet Aggregation Inhibitors; Retrospective Studies; Stents; Ticagrelor; Vascular Surgical Procedures

Standard dual antiplatelet therapy (DAPT) for complex aneurysms treated with flow diversion and flow disruption is acetylsalicylic acid (ASA) plus clopidogrel. However, clopidogrel resistance frequently occurs and can lead to thromboembolic events. Ticagrelor is an alternative not requiring platelet inhibition testing. We compared two DAPT regimens (ASA with clopidogrel or ticagrelor) on morbi-mortality, safety and efficacy of unruptured aneurysm embolization with flow diverter/disrupter.. This retrospective analysis of a 1:1 matched cohort compares patients treated with ASA + clopidogrel (March 2013-December 2015) vs. ASA + ticagrelor (January 2016-March 2017). No platelet inhibition testing was conducted. Patients matched for age (±10 years), type of treatment and aneurysm sac size ( ± 2 mm). Primary outcome measures were morbidity and mortality at 1-month; secondary outcomes were thromboembolic and hemorrhagic complications [on angiography and magnetic resonance imaging (MRI)] and groin complications. Outcomes were compared using bivariate analyses.. Ninety patients fulfilled inclusion criteria, of which 80 remained after matching (40 per group). There was no statistical difference in 1-month morbidity between the ticagrelor and clopidogrel groups (2.5% vs. 10%, P = 0.36) and no deaths reported. We observed no significant differences between ticagrelor and clopidogrel groups in terms of angiographic thromboembolic complications (5% vs. 12.5%, P = 0.43), territorial infarction on DWI (2.5% vs. 7.5%, P = 0.61), angiographic (0% vs. 0%, P = 1) and MRI (5% vs 5%, P = 1) hemorrhagic complications, new microbleeds (57.5% vs. 40%, P = 0.12) and groin puncture complications (2.5% vs. 0%, P = 1). At three months, there was no delayed territorial infarction or hemorrhage in either group.. Ticagrelor is safe and effective in replacing clopidogrel as DAPT for unruptured aneurysms.

Topics: Adult; Aneurysm, Ruptured; Clopidogrel; Cohort Studies; Embolization, Therapeutic; Female; Humans; Intracranial Aneurysm; Male; Middle Aged; Platelet Aggregation Inhibitors; Retrospective Studies; Ticagrelor; Treatment Outcome

The Pipeline Embolization Device™ (PED; Covidien Neurovascular Inc, Irvine, CA, USA) is a flow-diverting stent often used for the endovascular treatment of large or giant, wide-necked intracranial aneurysms of the internal carotid artery. Because of the inherent thrombogenicity of intracranial stents, dual-antiplatelet therapy is initiated after placement, which has been shown to decrease morbidity and mortality related to perioperative ischemic events in neurointerventional procedures. However, in some series, as much as 50% of patients demonstrate clopidogrel non-responsiveness. In these non-responders, alternate agents such as ticagrelor can be used to achieve adequate anticoagulation. Compared with clopidogrel, a prodrug requiring Cytochrome P450 enzymolysis for activation, ticagrelor directly and reversibly inhibits the P2Y12 ADP receptor. The absorption of the prodrug and the formation of its active metabolite is comparatively quicker ( t

Topics: Adenosine; Aged; Aspirin; Carotid Artery, Internal; Cerebral Angiography; Clopidogrel; Embolization, Therapeutic; Female; Humans; Intracranial Aneurysm; Platelet Aggregation Inhibitors; Purinergic P2Y Receptor Antagonists; Stroke; Ticagrelor; Ticlopidine

Thromboembolic complications constitute a significant source of morbidity after neurointerventional procedures. Flow diversion using the pipeline embolization device for the treatment of intracranial aneurysms necessitates the use of dual antiplatelet therapy to reduce this risk. The use of platelet function testing before pipeline embolization device placement remains controversial.. A retrospective review of prospectively maintained databases at 3 academic institutions was performed from the years 2009 to 2016 to identify patients with intracranial aneurysms treated with pipeline embolization device placement. Clinical and radiographic data were analyzed with emphasis on thromboembolic complications and clopidogrel responsiveness.. A total of 402 patients underwent 414 pipeline embolization device procedures for the treatment of 465 intracranial aneurysms. Thromboembolic complications were encountered in 9.2% of procedures and were symptomatic in 5.6%. Clopidogrel nonresponders experienced a significantly higher rate of thromboembolic complications compared with clopidogrel responders (17.4% versus 5.6%). This risk was significantly lower in nonresponders who were switched to ticagrelor when compared with patients who remained on clopidogrel (2.7% versus 24.4%). In patients who remained on clopidogrel, the rate of thromboembolic complications was significantly lower in those who received a clopidogrel boost within 24 hours pre-procedure when compared with those who did not (9.8% versus 51.9%). There was no significant difference in the rate of hemorrhagic complications between groups.. Clopidogrel nonresponders experienced a significantly higher rate of thromboembolic complications when compared with clopidogrel responders. However, this risk seems to be mitigated in nonresponders who were switched to ticagrelor or received a clopidogrel boost within 24 hours pre-procedure.

Topics: Adenosine; Adolescent; Adult; Aged; Aged, 80 and over; Clopidogrel; Embolization, Therapeutic; Female; Humans; Intracranial Aneurysm; Intracranial Embolism; Intracranial Thrombosis; Male; Middle Aged; Outcome Assessment, Health Care; Platelet Aggregation Inhibitors; Platelet Function Tests; Purinergic P2Y Receptor Antagonists; Retrospective Studies; Ticagrelor; Ticlopidine; Young Adult

Thromboembolic and hemorrhagic complications are among the most feared adverse events in the endovascular treatment of aneurysms, and this is particularly the case for flow diverter devices. Dual antiplatelet therapy has become standard of care; however, the safety, efficacy, and cost profiles of newer antiplatelet agents are not well characterized in the neurovascular context.. To compare the safety, efficacy, and cost of one of these newer agents, ticagrelor, to the most frequently used agent, clopidogrel.. A multicenter, retrospective, cohort comparison study design of consecutively treated aneurysms with flow diverter embolization device and treated with either ticagrelor or clopidogrel was performed. Data were collected on patient demographics and risk factors, procedural details, antiplatelet treatment regime, complications, and angiographic and functional outcomes.. Fifty patients undergoing flow diverter device deployment and treatment with ticagrelor were compared to 53 patients undergoing flow diversion and treatment with clopidogrel. The patients' age, sex, smoking status, aneurismal morphology and size, and procedural details did not differ between the 2 groups; neither did the rate of thromboembolic and hemorrhagic complications, angiographical, and functional outcomes. Ticagrelor was more expensive when compared to clopidogrel.. Ticagrelor is a safe and effective agent for prevention of thromboembolic complications following flow diverter deployment when compared to clopidogrel. However, ticagrelor remains significantly more expensive than clopidogrel, and, thus, we would advise ticagrelor be reserved for patients who are hyporesponsive to clopidogrel.

Topics: Adenosine; Adolescent; Adult; Aged; Aged, 80 and over; Clopidogrel; Cohort Studies; Drug Costs; Female; Humans; Intracranial Aneurysm; Male; Middle Aged; Platelet Aggregation Inhibitors; Prospective Studies; Retrospective Studies; Ticagrelor; Ticlopidine; Treatment Outcome; Young Adult