Safety and efficacy of cangrelor use in intracranial aneurysms: A Single-arm Meta-analysis and Systematic Review

Safety and efficacy of cangrelor use in intracranial aneurysms: A Single-arm Meta-analysis and Systematic Review | Authorea try { document.documentElement.classList.add('js'); } catch (e) { } var _gaq = _gaq || []; _gaq.push(['_setAccount', 'G-8VDV14Y67G']); _gaq.push(['_trackPageview']); (function() { var ga = document.createElement('script'); ga.type = 'text/javascript'; ga.async = true; ga.src = ('https:' == document.location.protocol ? 'https://ssl' : 'http://www') + '.google-analytics.com/ga.js'; var s = document.getElementsByTagName('script')[0]; s.parentNode.insertBefore(ga, s); })(); Skip to main content Preprints Collections Wiley Open Research IET Open Research Ecological Society of Japan All Collections About About Authorea FAQs Contact Us Quick Search anywhere Search for preprint articles, keywords, etc. Search Search ADVANCED SEARCH SCROLL This is a preprint and has not been peer reviewed. Data may be preliminary. 26 February 2026 V1 Latest version Share on Safety and efficacy of cangrelor use in intracranial aneurysms: A Single-arm Meta-analysis and Systematic Review Authors : Xinlu Wang 0000-0003-3151-7021 , Liangping Yu , Liu Haiyan , and Zhang Sixi [email protected] Authors Info & Affiliations https://doi.org/10.22541/au.177208398.83242374/v1 119 views 39 downloads Contents Abstract Information & Authors Metrics & Citations View Options References Figures Tables Media Share Abstract Background: Dual antiplatelet drugs are important for the treatment of intracranial aneurysms(IAs). However, postoperative complications(mainly Cerebral infarction and Cerebral hemorrhage) continued plaguing doctors and patients. Cangrelor was a newly developed intravenous P2Y12 receptor inhibitor in 2015. Its pharmacological action showed that it may be safer and more effective in the treatment of IAs. Therefore, we conducted a single arm meta-analysis and aystematic review to assess the feasibility of cangrelor in IAs. Data Sources and Methods: We searched PubMed, Cochrane, Web of Science and Embase and Embase for randomized clinical trials and nonrandomized studies of intervention including IAs patients who received cangrelor during operation. Statistical analysis was carried out using R software. Results: We included 6 studies comprising 115 patients. Median age ranged 56-61 from 41 to 86 years. In a pooled analysis, the preventing infarction effective rate of 98% (95% CI 0.93 to 1.00; I 2 =0%) and cerebral hemorrhage rate of 2% (95% CI 0.00 to 0.07; I 2 =25%). Conclusion: In the limited studies published so far, we tentatively believe that cangrelor is safe and effective in IAs. However, we still look forward to more relevant studies to help us further confirm, and the optimal treatment plan can be obtained. Introduction Intracranial aneurysm(IA) was a common neurovascular disease, which had a prevalence of about 2% of the population [1] . A rupture intracranial aneurysm can lead to intracranial hemorrhage or even death. For IA treatment, the methods had primary coil embolization, coiling with balloon assistance, stent-assisted coiling, intrasaccular flow disruptor placement, and parent artery flow diversion using braided stents [2] .We need antiplatelet therapy to prevent thrombosis when adopting stent-assisted coiling and flow diversion. Cangrelor is a relatively new IV ADP inhibitor that was approved for percutaneous coronary intervention (PCI) in 2015. It achieves antiplatelet effects rapidly and has a short half-life, which means it is useful and safety during perioperative period. There are several case series with respect to cangrelor in IA published. This article was looking forward to assessing the efficacy and safety of cangrelor. Material and Methods This systematic review and meta-analysis followed the recommendations of the Cochrane Handbook for Systematic Reviews of Interventions and the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) statement guidelines. Our study was not registered. Search strategy and data extraction We comprehensively searched PubMed, Cochrane Library,Web of Science and Embase, with the following search terms: (‘cangrelor’ OR ‘kengreal’ ) AND (‘Intracranial Aneurysm’). Search dates were from inception to 18 Nov 2023. Two authors independently searched and evaluated the quality according to unified standards. In case of disagreement, the other authors were invited to make a joint decision Selection criteria Type of studies We searched for published studies that contained safety or efficacy of cangrelor in IA wether rupture (RIA) or unrupture(UIA). Eligible studies included randomized controlled trials (RCTs) and non-RCTs (because published studies were too small). We excluded reviews, case reports(less than or equal to five cases) and nonhuman studies. Population of studies We included patients with intracranial aneurysm who underwent stents or flow diversions (FDs). Such patients routinely required dual antiplatelet therapy. Intervention intravenous cangrelor at any dosage during the operation. Outcomes Outcomes of interest comprised cerebral infarction, cerebral artery or occluded and in-stent restenosis. At least one of these outcomes was required. The primary adverse events were cerebral hemorrhage (included subarachnoid hemorrhage). The secondary adverse events were bleeding at other sites. Quality assessment We assessed the risk of bias using the Risk of Bias in Non-randomized Studies of Interventions (ROBINS-I) tool. Two authors evaluated the studies independently and discussed differences until all authors reached agreement. Statistical analysis This was a single-arm proportion meta-analysis investigating the efficacy and safety of cangrelor in intracranial aneurysm. Statistical analysis was carried out using R software and RStudio (version 2023.12.0+369). Random-effects modeling and 95% confidence interval (CI) were used for analysis. The results were presented as pooled analysis in forest plots. We used the Cochrane Q chi-square test and I 2 statistic to examine heterogeneity across studies; P values significant for heterogeneity. Results Our initial search included 3238 studies totally. 3209 studies were excluded after reading the titles and abstracts. After reading the full text, 23 studies were eliminated (Figure 1). Finally, 6 studies with 115 patients were included in our article. The characteristics of the included studies are described in Table 1. Figure 1 Preferred Reporting Items for Systematic Reviews and Meta Analysis (PRISMA) flow diagram of study screening and selection Table 1 Baseline characteristics of included studies Study Total Age median, y(range) Female Male RIA UIA Stents FDs follow-up time interval Abdennour, L 2020 [3] 7 56(41-64) 5 2 5 2 7 5 8.75 ± 10 mo Cagnazzo, F 2023 [4] 29 / / / 20 9 / / 24h Cheddad El Aouni, M 2022 [5] 15 61(45-63) 10 5 0 15 10 5 6mo Cortez, G. M 2021 [6] 24 57(28-86) 17 7 16 8 / 16 3mo Entezami, P 2023 [7] 33 60±22 28 5 21 12 17 16 3mo Godier, A 2019 [8] 7 56(50-61) 4 3 5 2 3 4 / EFFICACY Of the 115 patients included in the efficacy analysis of the studies. A pooled analysis revealed preventing infarction effective rate of 98% (95% CI 0.93 to 1.00; I 2 =0%), as depicted in Figure 2. Figure 2 Successful rate of preventing infarction SAFETY Of the 115 patients included in the safety analysis of the studies. A pooled analysis revealed cerebral hemorrhage rate of 2% (95% CI 0.00 to 0.07; I 2 =25%), as depicted in Figure 3. Figure 3 Cerebral Hemorrhage Rate Quality assessment All published studies were categorized as serious risk of bias (table 2), mainly beacuse of confounding. There were several uncertain or different factors, such as timing of cangrelor intravenous, duration, and changing to oral antiplatelet. We included too few studies and too few cases to perform further subgroup and sensitivity analyses. Considering heterogeneity is well, we stand by our results. Table 2 Risk of Bias Based on Robins-I Study Confounding Selection bias Bias in measurement classification of interventions Bias due to deviationsfrom intended interventions Bias due to missing data Bias in measurement of outcomes Bias in selection of the reported result Overall bias Abdennour, L 2020 [3] Serious Moderate Moderate Low Moderate Low Low Serious Cagnazzo, F 2023 [4] Serious Low Low Low Low Low Low Serious Cheddad El Aouni, M 2022 [5] Serious Serious Serious Low Low Low Low Serious Cortez, G. M 2021 [6] Serious Moderate Low Low Low Low Low Serious Entezami, P 2023 [7] Serious Low Low Low Low Low Low Serious Godier, A 2019 [8] Serious Low Low Low Low Low Low Serious Discussion The detection rate of intracranial aneurysms (IAs) is increasing, and the proportion of IAs concomitant with ischemic cardio-cerebrovascular diseases is correspondingly increasing. With the development of diagnosis and treatment, intracranial stent placement (included stent-assisted coiling and flow diversion) for the treatment of cerebral aneurysms is increasingly utilized. When we treated IAs with stents, we need dual antiplatelet therapy (DAPT) to prevent stent thrombosis. However antiplatelet drugs affected the natural history of IAs and the outcome of subarachnoid hemorrhage (SAH) had become a difficult problem in the management of patients with IAs. How to balance the risk of in-stent thrombosis and bleeding had become a major challenge in the current endovascular treatment of IAs [9] . Stent-assisted coil embolization and flow-diverter devices carried a high risk of thrombosis and often require DAPT or even triple antiplatelet therapy. Therefore this treatment was associated with a substantially increased risk of bleeding [10] . DAPT with aspirin and an oral P2Y12 receptor inhibitor (e.g. clopidogrel, ticagrelor, prasugrel) has become the standard medication regimen for nonemergent procedures [7] . In Chinese expert consensus, we recommend DAPT loading dose 2 hours before operation or normal dose DAPT plus tirofiban during operation, then normal DAPT [9] .Now we try to use cangrelor in place of tirofiban and oral P2Y12 receptor inhibitors for connecting normal DAPT after opration. Cangrelor was P2Y12 receptor inhibitors for injection. Therefore, it was considered whether it can replace the oral dosage form of similar drugs to achieve better efficacy. From the point of view of pharmacology, it seemed to work (table 3). All oral P2Y12 receptor inhibitors need several hours to get onset of effect (e.g. clopidogrel 2-8h, prasugrel 0.5-4h, ticagrelor 0.5-4h, tirofiban 5-30min), but cangrelor can take immediate effect (0-2min) as an injection [11] . Without doubt cangrelor had the minimum duration of effect during intravenous (e.g. cangrelor 30-60min, eptifibatide 4-6h, tirofiban 4-8h). That was to say, cangrelor was the fastest onset and the fastest failure during all antiplatelet wether oral or intravenous. Cangrelor seemed to bi the best and safest antiplatelet in the perioperative period theoretically. Cangrelor was a relatively new reversible antiplatelet agent listed in 2015, used in the cardiology field for PCI. Cangrelor had no indications in neurovascular so far, however antiplatelet drugs play a pivotal role in IAs. How can more effectively prevent thrombosis and reduce the risk of bleeding, cangrelor seemed to be a new good choice. Therefore, we expected this review to demonstrate whether cangrelor can be used in IAs. Table 3 Pharmacology and pharmacokinetics Clopidogrel Prasugrel Ticagrelor Tirofiban Cangrelor Class Thienopyridine Thienopyridine Triazolopyrimidine GPIIb/IIIa ATP analog Administration Oral Oral Oral Intravenous Intravenous Reversibity Irreversible Irreversible Reversible Reversible Reversible Onset of effect 2-8 h 30 min-4 h 30 min-4 h 5-30min 0–2 min Half-Life 6h 7h 8h 1.4-1.8h 2-5min Duration of effect 5-7d 7-10d 3-5d 4-8h 30-60min The results of Meta-analysis showed that the effective rate of cangrelor for IAs was 98%, and the bleeding rate was 2%. However, the number of included studies was too small, with only 115 patients, and the studies were not homogeneous. Therefore, we conduct a textual review for different situations. A total of 130 patients (including excluded articles) have been published, including 6 (4.6%) patients with infarction and 7 (5.4%) patients with bleeding (2 fatal, 1.5%) [3-8, 11-18] . In these studies, cangrelor was administered at different doses. Administer 30 µg/kg intravenous (IV) bolus prior to PCI followed immediately by a 4 µg/kg/min IV by instructions. Currently, there were no dose recommendations for intracranial aneurysms. Therefore, the subgroup was explored according to the dose (table 4). The number of participants was too small to perform statistical analysis, therefore, we were unable to explore which dose was more appropriate. Future studies are needed to address the dose issue. Table 4 Different Doses of cangrelor in Studies Dose of cangrelor Total Cerebral infarction Cerebral hemorrhage 30 µg/kg bolus followed by 4 µg/kg/min 29 2（6.9%） 5(17.2%) 15 µg/kg bolus followed by 2 µg/kg/min 2 0 0 30 µg/kg bolus followed by 2 µg/kg/min 1 0 0 Conclusion Based on limited datas, this article provisionally demonstrates the efficacy and safety of cangrelor in IAs. More studies are expected to confirm this. Ethics approval and consent to participate Not applicable Consent for publication All authors consent on publication. Author contributions Wang Xinlu and Zhang Sixi contributed to conception and design of the study. Wang Xinlu, Yu Liangping and Liu Haiyan performed the statistical analysis and wrote the first draft. All authors contributed to read, modified and approved the submitted version. Acknowledgements This was a self-initiated study with no funding. Disclosure/conflict of interest The authors have declared no conflicts of interest. Availability of data and material All datas were obtained from published studies. References [1] Radić B. Diagnostic and Therapeutic Dilemmas in the Management of Intracranial Aneurysms [J]. Acta Clinica Croatica, 2021.[2] Schirmer CM, Bulsara KR, Al-Mufti F, et al. Antiplatelets and Antithrombotics in Neurointerventional Procedures: Guideline Update [J]. J Neurointerv Surg, 2023, 15(11):1155-1162.[3] Abdennour L, Sourour N, Drir M, et al. Preliminary Experience with Cangrelor for Endovascular Treatment of Challenging Intracranial Aneurysms [J]. Clin Neuroradiol, 2020, 30(3):453-461.[4] Cagnazzo F, Radu RA, Derraz I, et al. Efficacy and Safety of Low Dose Intravenous Cangrelor in a Consecutive Cohort of Patients Undergoing Neuroendovascular Procedures [J]. J Neurointerv Surg, 2023.[5] Cheddad El Aouni M, Magro E, Abdelrady M, et al. Safety and Efficacy of Cangrelor among Three Antiplatelet Regimens During Stent-Assisted Endovascular Treatment of Unruptured Intracranial Aneurysm: A Single-Center Retrospective Study [J]. Front Neurol, 2022, 13727026.[6] Cortez GM, Monteiro A, Sourour N, et al. The Use of Cangrelor in Neurovascular Interventions: A Multicenter Experience [J]. Neuroradiology, 2021, 63(6):925-934.[7] Entezami P, Dalfino JC, Boulos AS, et al. Use of Intravenous Cangrelor in the Treatment of Ruptured and Unruptured Cerebral Aneurysms: An Updated Single-Center Analysis and Pooled Analysis of Current Studies [J]. J Neurointerv Surg, 2023, 15(7):669-673.[8] Godier A, Mesnil M, De Mesmay M, et al. Bridging Antiplatelet Therapy with Cangrelor in Patients with Recent Intracranial Stenting Undergoing Invasive Procedures: A Prospective Case Series [J]. Br J Anaesth, 2019, 123(1):e2-e5.[9] Drafting group of Chinese expert consensus on antiplatelet therapy for intracranial aneurysms. Chinese expert consensus on antiplatelet therapy for intracranial aneurysms [J]. Int J Cerebrovasc Dis, 2021, 29(9):646-653.[10] Hoh BL, Ko NU, Amin-Hanjani S, et al. 2023 Guideline for the Management of Patients with Aneurysmal Subarachnoid Hemorrhage: A Guideline from the American Heart Association/American Stroke Association [J]. Stroke, 2023, 54(7).[11] Aguilar-Salinas P, Agnoletto GJ, Brasiliense LBC, et al. Safety and Efficacy of Cangrelor in Acute Stenting for the Treatment of Cerebrovascular Pathology: Preliminary Experience in a Single-Center Pilot Study [J]. J Neurointerv Surg, 2019, 11(4):347-351.[12] Andresciani F, Pelle G, Messina M, et al. 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Neurocritical Care, 2018, 29(1):S218.[18] Wilson TA, Ramanathan D, Dye J. Ruptured Blister-Type Cerebral Aneurysm Pathogenesis and Treatment with Flow Diversion Using a Novel Antiplatelet Agent Cangrelor [J]. Interdisciplinary Neurosurgery-Advanced Techniques and Case Management, 2021, 25. Information & Authors Information Version history V1 Version 1 26 February 2026 Copyright This work is licensed under a Non Exclusive No Reuse License. Authors Affiliations Xinlu Wang 0000-0003-3151-7021 The First Hospital of Jilin University View all articles by this author Liangping Yu The First Hospital of Jilin University View all articles by this author Liu Haiyan The First Hospital of Jilin University View all articles by this author Zhang Sixi [email protected] The First Hospital of Jilin University View all articles by this author Metrics & Citations Metrics Article Usage 119 views 39 downloads .FvxKWukQNSOunydq8rnd { width: 100px; } Citations Download citation Xinlu Wang, Liangping Yu, Liu Haiyan, et al. Safety and efficacy of cangrelor use in intracranial aneurysms: A Single-arm Meta-analysis and Systematic Review. Authorea . 26 February 2026. DOI: https://doi.org/10.22541/au.177208398.83242374/v1 If you have the appropriate software installed, you can download article citation data to the citation manager of your choice. Simply select your manager software from the list below and click Download. 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