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Abstract 2-Thioadenosine monohydrate (1) is a vital intermediate in the synthesis of cangrelor. However, its industrial-scale preparation process and the analysis of the impurities formed during this process remained largely unknown. Herein, cangrelor was synthesized from oxidate adenosine, and the key step involved in the synthesis of compound 1 from intermediate 5. The effects of key synthesis parameters that influenced the reaction, including reaction temperature and time, were discussed. Moreover, four process-related impurities were purified, synthesized, and identified via nuclear magnetic resonance spectroscopy and high-resolution mass spectrometry. The process can be utilized to produce 1 on a kilogram scale, with a high-performance liquid chromatography purity of 98.0%. The study sheds light on and helps drug manufacturers further understand the formation process of impurities in the preparation of cangrelor.

An 84-year-old patient developed immediate thrombosis of his carotid stent in recovery after transcarotid artery revascularization. In the present report, the technical details about intraoperative management for neurovascular rescue using the transcarotid artery revascularization flow-reversal system are described. The patient was determined to have clopidogrel resistance. Intraoperative medical management is also discussed. The current alternative intravenous and oral antiplatelet therapies such as glycoprotein IIb/IIIa and P2Y12 inhibitors are explored. The debate regarding preoperative antiplatelet resistance testing remains ambiguous, and increasing studies have demonstrated the safety and efficacy of alternatives to clopidogrel. Despite an unpredictable and devastating complication, the patient’s outcome was successful using contemporary strategies.

In the setting of patients with indication to receive dual antiplatelet therapy undergoing surgery or invasive procedures, the risk of perioperative cardiac ischemic events, particularly stent thrombosis, is high, because surgery has a prothrombotic effect and antiplatelet therapy is withdrawn in order to avoid bleeding complications. Cangrelor, an intravenous P2Y12 receptor antagonist, has been tested in a randomized trial as a “bridge” to cardiac surgery from discontinuation of oral P2Y12 receptor antagonists. Thus, a consensus document extended its off-label use in this setting and before non-cardiac surgery. Currently, despite the implementation of a standardized bridging protocol with cangrelor, a residual risk of adverse outcome mainly due to bleeding events, still persist during the perioperative phase. Accordingly, a personalized management driven by platelet reactivity serial measurements and careful assessment of ischemic and bleeding risks has potential to optimize outcomes and costs as compared to a standardized bridging protocol, based on average pharmacodynamic data of oral P2Y12 inhibitors. While specific indications for bridging have been extensively addressed in the aforementioned consensus statement, the aim of the present document is the proposal of a “tailored” clinical decision-making algorithm inspired to the principle of personalized medicine dealing with complex clinical scenarios.

Utilization of cangrelor following coronary artery stent placement as a bridge to cardiac surgery has been previously described in the literature. However, the use of cangrelor as bridge therapy to cardiac surgery for endovascular revascularization is lacking. We describe a case involving a 47-year-old female who developed a left lower extremity tibioperoneal trunk non-obstructing arterial dissection following extracorporeal membrane oxygenation decannulation, requiring repair with a Viabahn endoprosthesis. To maintain stent patency, as well as treat the patient’s multi-vessel coronary disease and left ventricular thrombus, triple therapy with cangrelor, aspirin, and bivalirudin was utilized as the patient was optimized for a coronary artery bypass procedure. Our case describes a unique antiplatelet and anticoagulation strategy in a complex patient involving a multi-disciplinary team. [ABSTRACT FROM AUTHOR]

Pretreatment with a P2Y 12 inhibitor may be considered in patients with ST-segment elevation myocardial infarction (STEMI) referred to percutaneous coronary intervention (PCI). Intravenous cangrelor is an alternative in this setting, where oral absorption can be hindered. The aim of this study was to compare cangrelor administered after coronary angiography (i.e., "downstream") and ticagrelor pretreatment (i.e., "upstream"). STEMI patients undergoing PCI from October 2019 to June 2023 were included. The primary outcome was the composite of in-hospital major adverse cardiovascular events (MACE). Secondary outcomes included individual components of the primary outcome and in-hospital major bleeding. Univariable and multivariable regression analyses were performed in unmatched and propensity-matched cohorts. Of 6086 patients enrolled in the prospective CAST registry, 761 were included: 383 (50.3 %) received downstream cangrelor and 378 (49.7 %) upstream ticagrelor. In the matched population, no between-group differences were observed in MACE (odds ratio [OR] 1.30; 95 % confidence interval [CI] 0.79–2.17; P 0.308), all-cause death (OR 1.91; 95 % CI 0.87–4.54; P 0.124), myocardial infarction (OR 2.64; 95 % CI 0.76–12.14; P 0.154), stent thrombosis (OR 0.38; 95 % CI 0.06–1.80; P 0.255), unplanned repeat revascularization (OR 1.22; 95 % CI 0.32–4.98; P 0.766) and major bleeding (OR 0.98; 95 % CI 0.50–1.93; P 0.955). Cardiogenic shock and bailout administration of glycoprotein IIb/IIIa inhibitors were independent predictors of MACE, while radial access showed an inverse association with the primary outc. In P2Y 12 -naïve STEMI patients undergoing primary PCI, no significant differences were noted in the risk of in-hospital ischemic and bleeding events between downstream cangrelor and upstream ticagrelor. Abbreviations: adjOR, adjusted odds ratio; CI, confidence interval; GPI, glycoprotein IIb/IIIa inhibitors; MACE, major adverse cardiovascular events; OR, odds ratio; PCI, percutaneous coronary interventions; STEMI, ST-segment elevation myocardial infarction [Display omitted] • Oral pretreatment can be hindered in patients with ST-segment elevation myocardial infarction. • Previous did not specifically enroll STEMI patients, used mixed controls or did not define a specific administration timing for the oral drug. • In this propensity score-matched study, downstream cangrelor and upstream ticagrelor were associated with comparable in-hospital outcomes. • Downstream cangrelor represents a viable alternative when the oral administration route is not desirable or feasible. [ABSTRACT FROM AUTHOR]

Tools for precise prediction of bleeding risk in patients undergoing percutaneous coronary intervention (PCI) with cangrelor are lacking. Consecutive patients undergoing PCI and treated with cangrelor in 7 centers were retrospectively enrolled. The primary endpoint was Bleeding Academic Research Consortium (BARC) BARC 2, 3, or 5 bleeding 48 h after PCI. Predictors of BARC 2–5 bleeding were identified in a derivation cohort and combined into a numerical risk score. Discrimination and calibration were assessed in the derivation and validation cohorts. A threshold to define high bleeding risk (HBR) was identified and its diagnostic accuracy was compared with that of currently recommended bleeding risk scores. 1071 patients undergoing PCI with cangrelor were included. Fifty-four patients (5 %) experienced a BARC 2–5 bleeding, of whom 24 (44 %) from the access site. Age ≥ 75 years (odds ratio [OR] 2.58, 95 % confidence interval [CI] 1.21–5.48, p = 0.01), acute coronary syndrome at presentation (OR 8.14, 95 % CI 2.28–52, p = 0.01), and femoral access (OR 6.21, 95 % CI 2.71–14, p < 0.001) independently predicted BARC 2–5 bleeding at 48 h after PCI. The three items were combined to form a new risk score, the ICARUS score, showing good discrimination in both the derivation (area under the curve [AUC] 0.78) and internal validation (AUC 0.77) cohorts, and excellent calibration. An ICARUS score > 9 points accurately identified patients at HBR, showing better discrimination than other risk scores. A risk score based on age, clinical presentation and access site, predicts the risk of periprocedural bleeding in patients receiving cangrelor (ClinicalTrials.gov ID: NCT05505591). • Prediction of periprocedural bleeding in patients receiving cangrelor remains an unmet need. • A 3-item risk model accurately predicts bleeding in patients undergoing percutaneous coronary intervention and receiving cangrelor. • The accuracy of the proposed risk model outperforms current guideline-recommended models. [ABSTRACT FROM AUTHOR]

Abstract Background High on-treatment platelet reactivity (HTPR) remains a major problem in the acute management of ST-elevation myocardial infarction (STEMI), leading to higher rates of stent thrombosis and mortality. We aimed to investigate a novel, prehospital treatment strategy using cangrelor and tested its pharmacodynamic effects in a model using healthy volunteers. Methods We conducted a dose-finding, open-label, pilot trial including 12 healthy volunteers and tested three ascending bolus infusions of cangrelor (5 mg, 10 mg and 20 mg) and a bolus infusion followed by a continuous infusion via an intravenous (IV) flow regulator. Platelet function was assessed using multiple electrode aggregometry (MEA), vasodilator-stimulated phosphoprotein phosphorylation assay (VASP-P) and the platelet function analyzer. In an ex vivo experiment, epinephrine was used to counteract the antiplatelet effect of cangrelor. Results All cangrelor bolus infusions resulted in immediate and pronounced platelet inhibition. Bolus infusions of cangrelor 20 mg resulted in sufficient platelet inhibition assessed by MEA for 20 min in 90% of subjects. Infusion of cangrelor via the IV flow regulator resulted in sufficient platelet inhibition throughout the course of administration. Ex vivo epinephrine, in concentrations of 200 and 500 ng/mL was able to partially reverse the antiplatelet effect of cangrelor in a dose-dependent manner. Conclusions Weight-adapted bolus infusions followed by a continuous infusion of cangrelor via IV flow regulator result in immediate and pronounced platelet inhibition in healthy subjects. Cangrelor given as weight-adapted bolus infusion followed by a continuous infusion using an IV flow regulator may be a viable treatment approach for effective and well controllable prehospital platelet inhibition. Trial registration EC (Medical University of Vienna) 1835/2019 and EudraCT 2019-002792-34 .

There are no studies specifically designed to rule out a drug-drug interaction (DDI) when cangrelor is used among patients who have been pretreated with ticagrelor. This study sought to rule out a DDI among cangrelor-treated patients who have been pretreated with ticagrelor. In this prospective, randomized, double-blind, placebo-controlled, crossover, pharmacokinetic (PK) and pharmacodynamic (PD) study, patients with coronary artery disease (N = 20) were pretreated with a 180-mg ticagrelor loading dose and after 1 hour randomized to placebo or cangrelor (bolus and infusion for 2 hours). Patients crossed over after 1 to 4 weeks of washout. PK analysis included ticagrelor plasma levels and its active metabolite. PD assessments included VerifyNow P2Y 12 reaction units (PRU), light transmittance aggregometry, vasodilator-stimulated phosphoprotein, and Total Thrombus-Formation Analysis System. PK/PD assessments were performed at 7 time points. Compared with placebo, adding cangrelor to patients pretreated with ticagrelor resulted in a significant reduction in PRU at 30 minutes and 1 hour after starting infusion. At 2 hours after stopping cangrelor/placebo infusion, PRU were low and similar in both groups (16.9 vs 12.6; mean difference: 4.3; 95% CI: −28.6 to 37.3), meeting the noninferiority primary endpoint (predefined noninferiority margin 45 PRU). Consistent findings were shown with all PD assays. PK tracked PD findings with no differences between groups in plasma levels of ticagrelor and its metabolite. Compared with placebo, the use of cangrelor in patients pretreated with ticagrelor results in enhanced platelet inhibition with no differences in PK/PD profiles after discontinuation of drug infusion indicating the absence of a DDI. (PD and PK Profiles of Switching Between Cangrelor and Ticagrelor Following Ticagrelor Pre-treatment [SWAP-5]; NCT04634162) [Display omitted] [ABSTRACT FROM AUTHOR]

OBJECTIVE Systemic-to-pulmonary artery shunts are amongst the most common palliative procedures performed in neonates with congenital heart defects. These procedures require immediate postoperative thromboprophylaxis to prevent life-threatening shunt thrombosis. The novel use of intravenous P2Y12 platelet receptor antagonists has led to a need for dosing recommendations and monitoring. This study aims to determine cangrelor dosing in neonates through laboratory assessment of P2Y12 receptor reactivity and adverse events. METHODS Observational retrospective cohort study on the use of cangrelor for thromboprophylaxis in the immediate postoperative period of neonates undergoing placement of systemic-to-pulmonary artery shunts in a tertiary children's hospital from March 2020 to March 2021. RESULTS Ten neonates receiving cangrelor post systemic-to-pulmonary artery shunt placement were included in the study. Median age and weight were 4 days (IQR, 2.75-5.25) and 3.49 kg (IQR, 3.1-3.75), respectively. Five (50%) patients received a 3.5-mm shunt, while the remaining patients received a 4-mm shunt. For thrombin inhibition, 5 (50%) patients received heparin and 5 (50%) received bivalirudin. Median cangrelor dose was 0.1 mcg/kg/min (IQR, 0.1-0.1). Median achieved P2Y12 reaction units (PRU) at this cangrelor dose was 127.5 (IQR, 72.5-173.75). No shunt thrombosis occurred in these patients; however, there was 1 minor hemorrhagic event. CONCLUSIONS Our study suggests that a cangrelor dose of 0.1 mcg/kg/min is associated with therapeutic PRU and prevents shunt thrombosis in neonates post systemic-to-pulmonary artery shunt, with minimal hemorrhagic complications. ABBREVIATIONS ADP, adenosine diphosphate; CICU, cardiac intensive care unit; ECMO, extracorporeal membrane oxygenation; FFP, fresh frozen plasma; HLHS, hypoplastic left heart syndrome; IQR, interquartile range; PRBC, packed red blood cells; PRU, P2Y12 reaction units; PTT, partial thromboplastin time; S-PA, systemic-to-pulmonary artery; VAD, ventricular assist device [ABSTRACT FROM AUTHOR]

Novel P2Y12 ADP receptor blockers (ADPRB) should be preferred in dual-antiplatelet therapy in patients with acute coronary syndrome. Nevertheless, there are still patients who do not respond optimally to novel ADP receptor blocker therapy, and this nonoptimal response (so-called "high on-treatment platelet reactivity" or "resistance") could be connected with increased risk of adverse ischemic events, such as myocardial re-infarction, target lesion failure and stent thrombosis. In addition, several risk factors have been proposed as factors associated with the phenomenon of inadequate response on novel ADPRB. These include obesity, multivessel coronary artery disease, high pre-treatment platelet reactivity and impaired metabolic status for prasugrel, as well as elderly, concomitant therapy with beta-blockers, morphine and platelet count for ticagrelor. There is no literature report describing nonoptimal therapeutic response on cangrelor, and cangrelor therapy seems to be a possible approach for overcoming HTPR on prasugrel and ticagrelor. However, the optimal therapeutic management of "resistance" on novel ADPRB is not clear and this issue requires further research. This narrative review article discusses the phenomenon of high on-treatment platelet reactivity on novel ADPRB, its importance in clinical practice and approaches for its therapeutic overcoming. [ABSTRACT FROM AUTHOR]

According to the ESC guidelines, cangrelor may be considered in P2Y12-inhibitor-naïve acute coronary syndrome (ACS) patients undergoing percutaneous coronary intervention (PCI). The aim of this review is to summarize available evidence on the optimal maintenance therapy with P2Y12 receptor inhibitor after cangrelor. Transitioning from cangrelor to a thienopyridine, but not ticagrelor, can be associated with a drug-drug interaction (DDI); therefore, a ticagrelor loading dose (LD) can be given any time before, during, or at the end of a cangrelor infusion, while a LD of clopidogrel or prasugrel should be administered at the time the infusion of cangrelor ends or within 30 minutes before the end of infusion in the case of a LD of prasugrel. Administration of any oral antiplatelet agent at the end of a cangrelor infusion will also result in a transient period of increased platelet reactivity. The inter-individual variability of this period is difficult to predict because it depends on many factors related to the patient and the treatment. In addition, experimental studies indicate that cangrelor may exert a cardioprotective effect beyond the blockade of platelet aggregation. Considering the available data, the potential use of cangrelor in ACS patients goes well beyond the current indications. Furthermore, we believe that it might be prudent to avoid use of thienopyridines during and soon after a cangrelor infusion until conclusive data on the effect of the DDI on the clinical outcome are available. On the other hand, ticagrelor seems to be an optimal oral agent for continuation of P2Y12 inhibition in patients receiving cangrelor infusion.

The combination of clopidogrel and acetylsalicylic acid is the standard treatment for atherosclerotic cardiovascular disease. Nonetheless, there is a pressing need for more potent P2Y 12 receptor inhibitors with quicker onset, especially for early intervention in acute myocardial infarction. Integrating computational modeling, i.e. pharmacophore modeling, molecular docking, and dynamics, with empirical data guides the development of effective antiplatelet therapies. This multidisciplinary study employs computational modeling and in-vitro experimental analysis, demonstrating significant inhibition of P2Y 12 activity by two NCI compounds namely: NSC380324 and NSC618163. Both NSC380324 and NSC618163 exhibited a platelet reactivity index (%PRI) of 30.0% and 34.0%, respectively compared to cangrelor that demonstrated superior activity, with a %PRI of 11.0% in platelet vasodilator-stimulated phosphoprotein (VASP) assay. Molecular docking simulations show strong binding affinities of both compounds, along with strong binding interactions at the P2Y 12 binding site. Importantly, molecular dynamics simulations highlight the influence of receptor dynamics on practical efficacy, suggesting that NSC380324, a promising P2Y 12 antagonists indicated by its excellent stability profiles at the binding pocket of P2Y 12 , its hydrogen-bond interactions occupancies and the average MM-PBSA total binding energy of -38.17 kcal/mol, require further structural optimization and in-vivo studies to realize their full potential for clinical application.

Introduction: Cangrelor, the only intravenous platelet P2Y 12 receptor inhibitor, is characterized by a prompt and potent platelet inhibition, with a rapid offset of action. Large-scale clinical trials have shown that cangrelor reduce peri-procedural thrombotic events among patients undergoing percutaneous coronary interventions and not pre-treated with an oral P2Y 12 receptor inhibitor. However, high P2Y 12 receptor occupancy provided by cangrelor raises concerns for drug-drug interactions (DDIs) when transitioning to oral P2Y 12 inhibitors., Areas Covered: An understanding of the pharmacology of cangrelor and oral P2Y 12 inhibitors is essential to define the optimal approach to transition to oral P2Y 12 inhibitors without incurring the risk of DDIs. This review, based on a thorough literature search in major scientific databases (PubMed, Cochrane Library, Web of Science), synthesizes the pharmacology of cangrelor and the oral P2Y 12 receptor inhibitors, providing the rationale for the occurrence of DDIs and strategies to avoid such risk., Expert Opinion: The timing of transition from cangrelor to oral P2Y 12 inhibitors plays a crucial role in the occurrence of DDIs, especially with clopidogrel and prasugrel. Currently, no evidence suggests a DDI when transitioning to ticagrelor. Adhering to product labels and guideline recommendations is crucial for optimizing safety and efficacy of cangrelor.

Background : Cangrelor provides rapid platelet inhibition, making it a potential option for out-of-hospital cardiac arrest (OHCA) survivors undergoing percutaneous coronary intervention (PCI). However, clinical data on its use after OHCA are limited. This study investigates in-hospital outcomes of cangrelor use in this population. Methods : We conducted a prospective, observational study involving OHCA patients from the Lombardia CARe Registry (January 2015-December 2022) who underwent PCI in seven centers in Northern Italy. Propensity score (PS) matching compared patients who received cangrelor to those who did not. Logistic regression tested associations between cangrelor and discharge outcomes. Results : Of 612 OHCA patients admitted, 414 (67.4%) underwent PCI with known antithrombotic therapy, of whom 34 (8.2%) received cangrelor. Radial access was more common in the cangrelor group, which also had a higher troponin peak and a final TIMI flow grade of 3. Survival at discharge was 82.4% in the cangrelor group, compared to 65.3% in the no-cangrelor group ( p = 0.043). Univariable logistic regression showed that cangrelor use was associated with higher survival at discharge (OR 2.5; 95% CI: 1.1-6.1, p = 0.049). After multiple PS matchings, cangrelor remained associated with better survival (OR 2.07; 95% CI: 1.16-2.98). Major bleeding rates were higher in the cangrelor group, even after adjusting for baseline bleeding risk (OR: 7.0; 95% CI: 2.9-17.0; p < 0.001). Conclusions : In OHCA patients undergoing PCI, cangrelor use was linked to improved in-hospital survival but higher major bleeding, suggesting a potential net clinical benefit.

Outcome data on using cangrelor in older patients are limited. This post hoc analysis of the itAlian pRospective Study on CANGrELOr (ARCANGELO) study aims to assess bleeding and ischemic outcomes with the transition from cangrelor to any oral P2Y 12 inhibitors in age-stratified subgroups (≥75 years-older, <75 years-younger) of patients with acute coronary syndrome who underwent percutaneous coronary intervention (PCI). Of 995 patients, 215 (21.6%) were older, 115 of whom (11.6%) were aged ≥80 years. Presentation with ST-elevation myocardial infarction was less frequent in older than in younger patients (52.6% vs 62.1%, p = 0.0119). At 30 days after PCI, rates of the study's primary end point of overall bleeding defined according to the Bleeding Academic Research Consortium were not significantly different between the 2 age subgroups (4.6% in the younger vs 7.4% in the older, p = 0.1179). Rates of major adverse cardiac events, defined as the composite of death, myocardial infarction, ischemia-driven revascularization, and stent thrombosis, were significantly lower in younger than in older patients (0.9% vs 3.3%, p = 0.0170). Intraprocedural thrombotic events occurring in the 48 hours after PCI arose in similar proportions in the subgroups (1.4% vs 1.4%, p = 1.000). In conclusion, these data suggest that using cangrelor with transition to any oral P2Y12 inhibitor is a safe and effective antithrombotic treatment in older patients who undergo PCI for acute coronary syndrome in the setting of routine clinical practice. Clinical Trial Registration Number: NCT04471870., Competing Interests: Declaration of competing interest Dr. Capranzano has received personal speaker fees from Daiichi Sankyo, Amgen, and Bayer. Dr. Di Mario has received research or educational grants from Abbott, Amgen, Asahi Intecc, AstraZeneca, Boston Scientific, Cardinal Health, CSL Behring, Chiesi, Daiichi Sankyo, Edwards, Medtronic, Menarini, Pfizer, Sanofi, Shockwave, Teleflex, and Volcano/Philips. Dr. De Luca has received consulting fees or honoraria from Amgen, Aspen, AstraZeneca, Bayer, Boehringer Ingelheim, Chiesi, Daiichi Sankyo, Eli Lilly, Menarini, Pfizer/Bristol‐Myers Squibb, Sanofi, Servier, and The Medicines Company, outside the present work. The remaining authors have no competing interests to declare., (Copyright © 2024 Elsevier Inc. All rights reserved.)

We herein report the case of a pediatric patient suffering from subarachnoid hemorrhage (SAH) due to a ruptured internal carotid artery (ICA) saccular aneurysm. Considering the unfavorable anatomy and irregular shape of the aneurysm, a flow diverter (FD) stent was positioned in addition to coils in an acute setting. Cangrelor (Kengreal, Chiesi, USA) IV bolus followed by maintenance IV infusion was administered in addition to ASA at the time of intervention. Transitioning from cangrelor to thienopyridine (clopidogrel) was done the day after the procedure without any ischemic or hemorrhagic complications. The patient was discharged symptom-free 24 days later. We discuss technical considerations focusing specifically on antiplatelet therapy management., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Platelets play a key role in arterial thrombosis and antiplatelet therapy is pivotal in the treatment of cardiovascular disease. Current antiplatelet drugs target different pathways of platelet activation and show specific pharmacodynamic and pharmacokinetic characteristics, implicating clinically relevant drug–drug interactions. This article reviews the role of platelets in hemostasis and cardiovascular thrombosis, and discusses the key pharmacodynamics, drug–drug interactions and reversal strategies of clinically used antiplatelet drugs. Antiplatelet therapies target distinct pathways of platelet activation: thromboxane A2 synthesis, adenosine diphosphate-mediated signaling, integrin αIIbβ3 (GPIIb/IIIa), thrombin-mediated platelet activation via the PAR1 receptor and phosphodiesterases. Key clinical drug–drug interactions of antiplatelet agents involve acetylsalicylic acid – ibuprofen, clopidogrel – omeprazole, and morphine – oral P2Y12 inhibitors, all of which lead to an attenuated antiplatelet effect. Platelet function and genetic testing and the use of scores (ARC-HBR, PRECISE-DAPT, ESC ischemic risk definition) may contribute to a more tailored antiplatelet therapy. High on-treatment platelet reactivity presents a key problem in the acute management of ST-elevation myocardial infarction (STEMI). A treatment strategy involving early initiation of an intravenous antiplatelet agent may be able to bridge the gap of insufficient platelet inhibition in high ischemic risk patients with STEMI. [ABSTRACT FROM AUTHOR]

Background: The itAlian pRospective Study on CANGrELOr (ARCANGELO) was aimed to assess the safety of using cangrelor during percutaneous coronary intervention (PCI) in patients with acute coronary syndromes (ACS) in the daily practice. Hypothesis: The safety of cangrelor after the transition to oral P2Y12 inhibitors was evaluated as the incidence of bleeding outcomes in the 30 days following PCI according to postauthorization safety study guidelines. Methods: Adults with ACS who were treated with cangrelor in one of the 28 centers involved in the study. Patients who consented to participate were followed in the 30 days following their PCI. Bleedings (Bleeding Academic Research Consortium [BARC] classification), major adverse cardiac events (MACEs), and adverse events were recorded. The interim results at two‐thirds of the enrollment period are presented. Results: A total of 17 bleedings were observed in the 320 patients who completed the study at this stage. All bleedings were classified as BARC Type 1–2, except for one case of Type 3a (vessel puncture site hematoma). Four patients experienced MACEs (2 acute myocardial infarctions, 1 sudden cardiac death, 1 noncardiovascular death due to respiratory distress, and multiorgan failure). None of the bleedings was rated as related to cangrelor. Conclusions: The interim results of the ARCANGELO study provide a preliminary confirmation that the use of cangrelor on patients with ACS undergoing PCI is not associated with severe bleedings. [ABSTRACT FROM AUTHOR]

Abstract Background Sepsis is a common complication of severe wound injury and infection, with a very high mortality rate. The P2Y12 receptor inhibitor, cangrelor, is an antagonist anti-platelet drug. Methods In our study, we investigated the protective mechanisms of cangrelor in CLP-induced pulmonary injury in sepsis, using C57BL/6 mouse models. Results TdT-mediated dUTP Nick-End Labeling (TUNEL) and Masson staining showed that apoptosis and fibrosis in lungs were alleviated by cangrelor treatment. Cangrelor significantly promoted surface expression of CD40L on platelets and inhibited CLP-induced neutrophils in Bronchoalveolar lavage fluid (BALF) (p

In December 2019, an outbreak of pneumonia caused by a novel coronavirus occurred in Wuhan, Hubei province, spreading rapidly first throughout China and subsequently across Europe, the United States (US), and the rest of the world. On January 30, 2020, the World Health Organization (WHO) declared the COVID-19 outbreak a public health emergency of international concern, and on March 12, 2020, it was characterized as a pandemic. Patients exposed to this virus named as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) frequently present with fever, cough, and shortness of breath within 2 to 14 days after exposure, and then usually develop coronavirus disease (COVID-19)-related pneumonia. Although respiratory symptoms prevail among all clinical manifestations of COVID-19, preliminary studies showed that some patients may develop severe cardiovascular (CV) damage. To date, the COVID-19 pandemic has caused significant changes in the prevalence and pathogenesis of cardiovascular diseases among the population in Ukraine and other countries and has led to a significant increase in mortality in this category of patients. These changes necessitated adjustment of drug treatment in patients with concomitant COVID-19. Conclusions. COVID-19 is a global pandemic with unpredictable consequences due to mutually reinforcing damage to the respiratory and cardiovascular systems. Treatment of acute coronary syndrome on the background of COVID-19 requires a systematic approach involving physicians of various specialties as well as compliance with anti-epidemic mea- sures. Interventional treatment is quite effective in treating patients with COVID-associated acute coronary syndrome. COVID-19 patients on mechanical ventilation should use intravenous P2Y12 receptor blockers or drugs that can be crushed and administered through a nasogastric tube. Cangrelor, an intravenous P2Y12 receptor blocker with fast action and high controllability, enabled to achieve the optimal result of the intervention.

Abstract Background Despite the advances of potent oral P2Y12 inhibitors, their onset of action is delayed, which might have a negative impact on clinical outcome in patients undergoing percutaneous coronary intervention (PCI). Trials conducted in the United States of America have identified cangrelor as a potent and rapid-acting intravenous P2Y12 inhibitor, which has the potential of reducing ischemic events in these patients without an increase in the bleeding. As cangrelor is rarely used in The Netherlands, we conducted a nationwide registry to provide an insight into the use of cangrelor in the management of patients with suboptimal platelet inhibition undergoing (primary) PCI (the Dutch Cangrelor Registry). Study design The Cangrelor Registry is a prospective, observational, multicenter, single-arm registry with cangrelor administered pre-PCI in: (1) P2Y12 naive patients with ad-hoc PCI, (2) patients with STEMI/NSTEMI with suboptimal P2Y12 inhibition including (3) stable resuscitated/defibrillated patients with out-of-hospital cardiac arrest (OHCA) due to acute ischemia and (4) STEMI/NSTEMI patients with a high thrombotic burden. Primary endpoint is 48 h Net Adverse Clinical Events (NACE), which is a composite endpoint of all-cause death, recurrent myocardial infarction (MI), target vessel revascularization (TVR), stroke, stent thrombosis (ST) and BARC 2-3-5 bleeding. Summary The Dutch Cangrelor Registry will assess the feasibility and safety of cangrelor in patients with suboptimal P2Y12 inhibition undergoing (primary) PCI in the setting of acute coronary syndrome (ACS) and stable coronary artery disease (CAD) in the Netherlands.

In the setting of patients with indication to receive dual antiplatelet therapy undergoing surgery or invasive procedures, the risk of perioperative cardiac ischemic events, particularly stent thrombosis, is high, because surgery has a prothrombotic effect and antiplatelet therapy is withdrawn in order to avoid bleeding complications. Cangrelor, an intravenous P2Y12 receptor antagonist, has been tested in a randomized trial as a "bridge" to cardiac surgery from discontinuation of oral P2Y12 receptor antagonists. Thus, a consensus document extended its off-label use in this setting and before non-cardiac surgery. Currently, despite the implementation of a standardized bridging protocol with cangrelor, a residual risk of adverse outcome mainly due to bleeding events, still persist during the perioperative phase. Accordingly, a personalized management driven by platelet reactivity serial measurements and careful assessment of ischemic and bleeding risks has potential to optimize outcomes and costs as compared to a standardized bridging protocol, based on average pharmacodynamic data of oral P2Y12 inhibitors. While specific indications for bridging have been extensively addressed in the aforementioned consensus statement, the aim of the present document is the proposal of a "tailored" clinical decision-making algorithm inspired to the principle of personalized medicine dealing with complex clinical scenarios. [ABSTRACT FROM AUTHOR]

Background In clinical trials, cangrelor has been shown to reduce percutaneous coronary intervention–related ischemic complications without increasing major bleeding. This study was performed to examine cangrelor use and transition to oral P2Y12 inhibitors in routine clinical practice. Methods and Results The CAMEO (Cangrelor in Acute Myocardial Infarction: Effectiveness and Outcomes) registry is a multicenter, retrospective observational study of platelet inhibition strategies for patients with myocardial infarction undergoing percutaneous coronary intervention. In phase 1, data were collected on consecutive patients with myocardial infarction (n=482) treated with any P2Y12 inhibitor to understand cangrelor use by hospital. In phase 2, data were collected in a 2:1 (cangrelor‐: non‐cangrelor‐treated) ratio of patients with myocardial infarction (n=873). In phase 1, cangrelor use varied across hospitals (overall, 50.4% [range, 6.0%–100%]). Of patients receiving cangrelor in both phases (n=819), 3.3% received either the bolus or infusion only. Cangrelor was infused for a median of 121 (76–196) minutes; and 38.3% received an infusion for 1‐hour gap between cangrelor cessation and oral P2Y12 inhibitor initiation; this was highest among those transitioned to clopidogrel (56.6% versus 34.5% prasugrel versus 10.8% ticagrelor; P

Nowadays, cangrelor is still the only intravenous antiplatelet drug that belongs to the P2Y12 inhibitors family. Its unique charac‑ teristics are possibilities of intravenous application and rapid onset and offset of action. In this case, we would like to present a patient with acute myocardial infarction in whom percutaneous coronary intervention could be very dangerous without the use of cangrelor. The reason was very high ischemic risk during complex coronary intervention. In addition to this indication, cangrelor could be very useful in other situations, when intravenous administration is the only way to inhibit platelets. [ABSTRACT FROM AUTHOR]

Irene Lizano-Díez,1 Silvia Paz Ruiz2 1Ferrer, Barcelona, Spain; 2SmartWorking4U SLU, Benicàssim, SpainCorrespondence: Irene Lizano-DíezFerrer, Av Diagonal 549, Barcelona 08029, SpainTel +34 93 600 37 00Email ilizano@ferrer.comPurpose: Cangrelor is an intravenous, direct-acting, reversible P2Y12 inhibitor indicated for the reduction of thrombotic cardiovascular events in patients with coronary artery disease (CAD) undergoing percutaneous coronary intervention (PCI) in whom oral P2Y12 inhibitors are not feasible or desirable. The objective was to assess the financial impact of introducing cangrelor into the hospital formulary in Spain.Patients and Methods: A budget impact model was developed to calculate the cost difference between two scenarios (without and with cangrelor) to treat CAD patients undergoing PCI in whom oral P2Y12 inhibitors are not feasible or desirable, over 3 years. Intravenous P2Y12 inhibitor (cangrelor), oral P2Y12 inhibitors (clopidogrel, prasugrel, and ticagrelor), and glycoprotein IIb-IIIa inhibitors (GPIs) for bail-out use were considered. Epidemiological, efficacy (thrombotic events including cardiac death), safety (bleeding events), and costs (€, 2019) data were based on Spanish registries, clinical trials, and meta-analyses. One-way sensitivity analysis established the effect of uncertainty on results.Results: For years 1, 2, and 3, the target population to receive cangrelor was 607, 1,822, and 3,340 patients, and cangrelor uptake was 23.70%, 58.30%, and 51.30%, respectively. The 3-year budget impact was 1,021,717€ varying from 50,245€ in year 1 to 599,272€ in year 3. The results were sensitive to the number of patients treated with GPIs in Spanish hospitals.Conclusion: Based on our results, the financial effort needed to introduce the use of cangrelor in patients undergoing PCI in whom antiplatelet therapy with oral P2Y12 inhibitors is not feasible or desirable barely exceeds one million € over three years, in Spain.Keywords: P2Y12 inhibitors, cangrelor, percutaneous coronary intervention, budget impact

Background: High on-treatment platelet reactivity (HTPR) remains a major problem in the acute management of ST-elevation myocardial infarction (STEMI), leading to higher rates of stent thrombosis and mortality. We aimed to investigate a novel, prehospital treatment strategy using cangrelor and tested its pharmacodynamic effects in a model using healthy volunteers. Methods: We conducted a dose-finding, open-label, pilot trial including 12 healthy volunteers and tested three ascending bolus infusions of cangrelor (5 mg, 10 mg and 20 mg) and a bolus infusion followed by a continuous infusion via an intravenous (IV) flow regulator. Platelet function was assessed using multiple electrode aggregometry (MEA), vasodilator-stimulated phosphoprotein phosphorylation assay (VASP-P) and the platelet function analyzer. In an ex vivo experiment, epinephrine was used to counteract the antiplatelet effect of cangrelor. Results: All cangrelor bolus infusions resulted in immediate and pronounced platelet inhibition. Bolus infusions of cangrelor 20 mg resulted in sufficient platelet inhibition assessed by MEA for 20 min in 90% of subjects. Infusion of cangrelor via the IV flow regulator resulted in sufficient platelet inhibition throughout the course of administration. Ex vivo epinephrine, in concentrations of 200 and 500 ng/mL was able to partially reverse the antiplatelet effect of cangrelor in a dose-dependent manner. Conclusions: Weight-adapted bolus infusions followed by a continuous infusion of cangrelor via IV flow regulator result in immediate and pronounced platelet inhibition in healthy subjects. Cangrelor given as weight-adapted bolus infusion followed by a continuous infusion using an IV flow regulator may be a viable treatment approach for effective and well controllable prehospital platelet inhibition. Trial registration: EC (Medical University of Vienna) 1835/2019 and EudraCT 2019-002792-34. [ABSTRACT FROM AUTHOR]

Introduction: Thromboembolic events represent the most frequent complications of endovascular treatment of unruptured intracranial aneurysm using stent-assisted coilling or flow diverter stents. Dual antiplatelet therapy has become the standard to prevent these but remains unstandardized. We present here a single center experience of 3 standardized antiplatelet regimens during brain aneurysm treatment, while emphasizing the use of the Cangrelor. Method: We retrospectively reviewed data from patients treated using stent-assisted coilling or flow diverter stents from 2016 to 2021. We collected and compared safety and efficacy data within 6 months of three groups of patients corresponding to three antiplatelet standardized regimens: group T with Ticagrelor, with preprocedural preparation; group E with Eptifibatide, injected during procedure; group C with Cangrelor, injected during procedure. Results: Data of 112 patients were analyzed and 76 belonged to group T, 21 to group E, and 15 to group C. Eleven events over the 14 recorded were adjudicated to be related to antiplatelets, their repartition did not differ between the 3 groups (p = 0.43). All symptomatic events (N = 8) were not distributed significantly differently between the 3 groups (p = 0.11) and asymptomatic events were also balanced (p = 1.00). Of these, 6 subjects had a change in the mRS score at 3–6 months. Thrombo-embolic events represented the most encountered events in the sample: 2 acute ischemic strokes were recorded in group E and 1 in group T; 1 transient ischemic stroke was noted in group E; 4 silent infarcts were found on control MRI (2 belonged to group T, 1 to group E and 1 to group C). Among 3 intracranial bleeding events, 1 was symptomatic in group C, 2 were asymptomatic in group T. On the control evaluation performed at 6 months, there was no significant difference on aneurysmal occlusion (p = 0.67). Conclusion: This single-center retrospective study compared 3 antiplatelet regimens, finding no significant difference in the safety and efficacy in the context of endovascular treatments of unruptured aneurysm using stent or flow diverters. This study adds data for the Cangrelor use and suggests its usefulness in the field of neuro-endovascular intervention. Randomized controlled studies are warranted to confirm these results. [ABSTRACT FROM AUTHOR]

Background: Management of dual antiplatelet therapy (DAPT) in the perioperative setting is challenging, particularly in complex patient populations, such as those with underlying coagulopathy and/or recent percutaneous coronary interventions. Methods: In this case series, we describe the perioperative use of cangrelor bridge therapy in two patients undergoing liver transplantation after recent coronary drug‐eluting stent placement. Outcomes: In both patient cases, cangrelor use as a P2Y12 bridge at a dose of 0.75 μg/kg/min was safe and effective. Both patients were successfully switched back to their oral DAPT regimen post‐operatively without additive bleeding or thrombotic complications. Conclusion: The use of cangrelor as bridge therapy in high‐risk perioperative liver transplant patients appears to be a viable option when DAPT is warranted. [ABSTRACT FROM AUTHOR]

Cangrelor is an intravenously administered P2Y12 receptor antagonist, which has been approved for adult patients undergoing percutaneous coronary intervention and, due to its unique pharmacokinetics, it allows effective and controllable peri-procedural platelet inhibition. We report the case of a 6-year-old child with anomalous origin of right coronary artery from aortic left coronary sinus, who underwent elective surgical replacement of stenotic and calcified conduit between the right ventricle and the main pulmonary artery. The surgery was complicated by acute myocardial infarction secondary to coronary extrinsic compression. The patient was successfully treated with urgent percutaneous coronary intervention (simultaneous V-stenting) and cangrelor infusion, subsequently switched to clopidogrel therapy.

IntroductionThromboembolic events represent the most frequent complications of endovascular treatment of unruptured intracranial aneurysm using stent-assisted coilling or flow diverter stents. Dual antiplatelet therapy has become the standard to prevent these but remains unstandardized. We present here a single center experience of 3 standardized antiplatelet regimens during brain aneurysm treatment, while emphasizing the use of the Cangrelor.MethodWe retrospectively reviewed data from patients treated using stent-assisted coilling or flow diverter stents from 2016 to 2021. We collected and compared safety and efficacy data within 6 months of three groups of patients corresponding to three antiplatelet standardized regimens: group T with Ticagrelor, with preprocedural preparation; group E with Eptifibatide, injected during procedure; group C with Cangrelor, injected during procedure.ResultsData of 112 patients were analyzed and 76 belonged to group T, 21 to group E, and 15 to group C. Eleven events over the 14 recorded were adjudicated to be related to antiplatelets, their repartition did not differ between the 3 groups (p = 0.43). All symptomatic events (N = 8) were not distributed significantly differently between the 3 groups (p = 0.11) and asymptomatic events were also balanced (p = 1.00). Of these, 6 subjects had a change in the mRS score at 3–6 months. Thrombo-embolic events represented the most encountered events in the sample: 2 acute ischemic strokes were recorded in group E and 1 in group T; 1 transient ischemic stroke was noted in group E; 4 silent infarcts were found on control MRI (2 belonged to group T, 1 to group E and 1 to group C). Among 3 intracranial bleeding events, 1 was symptomatic in group C, 2 were asymptomatic in group T. On the control evaluation performed at 6 months, there was no significant difference on aneurysmal occlusion (p = 0.67).ConclusionThis single-center retrospective study compared 3 antiplatelet regimens, finding no significant difference in the safety and efficacy in the context of endovascular treatments of unruptured aneurysm using stent or flow diverters. This study adds data for the Cangrelor use and suggests its usefulness in the field of neuro-endovascular intervention. Randomized controlled studies are warranted to confirm these results.

Antiplatelet therapy involving aspirin and a P2Y 12 receptor inhibitor is fundamental in managing patients with atherothrombotic disease. Switching between P2Y 12 inhibitors is frequently observed in clinical settings for various reasons, such as safety, efficacy, patient adherence, or cost concerns. Although it occurs often, the optimal method for switching remains a concern owing to potential drug interactions, which can result in either inadequate platelet inhibition and subsequent thrombotic events or low platelet reactivity and increased bleeding risks due to therapy overlap. This review offers practical guidance on switching P2Y 12 inhibitors, drawing from pharmacodynamic and clinical data., Competing Interests: Disclosures Dr F. Franchi has received consulting fees or honoraria from AstraZeneca; and institutional grants from PLx Pharma and the Scott R. MacKenzie Foundation. Dr D.J. Angiolillo has received consulting fees or honoraria from Abbott, Amgen, AstraZeneca, Bayer, Biosensors, Boehringer Ingelheim, Bristol Myers Squibb, Chiesi, CSL Behring, Daiichi-Sankyo, Eli Lilly, Faraday, Haemonetics, Janssen, Merck, Novartis, PhaseBio, PLx Pharma, Pfizer, and Sanofi; and has received institutional research grants from Amgen, AstraZeneca, Bayer, Biosensors, CeloNova, CSL Behring, Daiichi-Sankyo, Eisai, Eli Lilly, Faraday, Gilead, Idorsia, Janssen, Matsutani Chemical Industry Co., Merck, Novartis, and the Scott R. MacKenzie Foundation. Dr D. Sibbing has received speaker fees and fees for advisory board activities from Bayer, Daiichi-Sankyo, and Sanofi. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Introduction: Dual antiplatelet therapy (DAPT) with aspirin and a P2Y 12 inhibitor is the standard of care for patients who undergo percutaneous coronary intervention (PCI) for ST elevation myocardial infarction (STEMI). Though this regimen reduces rates of ischemic events in patients with STEMI, the optimal strategy for P2Y 12 administration in STEMI patients is still evolving., Purpose: The purpose of this review is to summarize current evidence on optimal use of ticagrelor and prasugrel in the acute phase of STEMI., Summary: Due to high platelet activity in the acute setting of STEMI and PCI, adequate and rapid platelet inhibition is important. Strategies of increased ticagrelor/prasugrel loading dose or earlier administration in STEMI have not been successful in closing this platelet inhibition gap. Potential strategies for improving ticagrelor/prasugrel use early in STEMI include bridging with intravenous antiplatelet agents or crushed or chewed administration., Conclusion: Oral ticagrelor/prasugrel given before or immediately after STEMI PCI is usually sufficient to prevent thrombotic complications. When faster platelet inhibition is desired, or oral administration is compromised by inability to swallow tablets, crushing/chewing ticagrelor/prasugrel tablets is an alternative to intravenous P2Y 12 inhibitor therapy., Competing Interests: Declaration of competing interest The authors have no relevant financial or non-financial interests to disclose., (Copyright © 2024 Elsevier Inc. All rights reserved.)

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Background: Patients with STEMI receive dual antiplatelet therapy as soon as possible with aspirin and a P2Y12 receptor antagonist prior to PCI. A fraction of these patients may have multi-vessel disease needing emergent CABG surgery. The choice of a P2Y12 receptor antagonist plays a role in the timing of CABG surgery as it poses a bleeding risk until it is completely eliminated from the system. Oral P2Y12 receptor antagonists have a long duration of platelet inhibition which is difficult to reverse. Cangrelor is an intravenous P2Y12 receptor antagonist with a short half-life and rapid cessation of its effect after discontinuation. Methods: Three patients who presented to our emergency department with STEMI were started on cangrelor infusion prior to cardiac catheterization instead of other P2Y12 receptor antagonists like clopidogrel or ticagrelor. The study received ethical approval as it is part of the current standard of care for STEMI patients. Results: All three patients were found to have multi-vessel disease during coronary angiography requiring CABG surgery. As cangrelor was used in these patients they were able to have their surgery within 24–48 h. Intravenous cangrelor was stopped about an hour before surgery. No bleeding complications occurred and all three patients made a speedy recovery in the ICU. Conclusion: Cangrelor is a potent P2Y12 receptor antagonist which can be used in patients presenting with STEMI as one of the two anti-platelet agents along with aspirin without any dilemma that it would cause a delay in CABG surgery if the patients need one.

Introduction: Emergent stenting of both extra- and intracranial occlusions during acute ischemic stroke procedures is complicated by the need for immediate platelet inhibition to prevent thromboembolic complications. IV cangrelor is a relatively new antiplatelet that was initially approved for coronary interventions. Five prior case series have been published evaluating the results of IV cangrelor in neurointerventional procedures. We sought to combine the data from all prior studies and analyze only ischemic stroke interventions. Methods: A prospectively maintained database was reviewed to identify all cases of IV cangrelor administration during acute ischemic stroke intervention. Nine additional patients were identified who have not been previously published. In addition, a literature search was performed to identify five prior publications of cangrelor in neurointervention. The data from these was combined with our institution in a pooled-analysis. Results: Overall, 129 patients who received IV cangrelor during an acute ischemic stroke intervention were identified. The asymptomatic intracranial hemorrhage rate was 12.6%(11/87). The symptomatic intracranial hemorrhage rate was 6.2% (8/129). The rate of retroperitoneal hematoma and gastrointestinal bleeding were also low (1.5% and 0.8%, 2/129 and 1/129). There was one case of intraprocedural thromboembolic complication (0.8%) and no cases of intraprocedural in-stent thrombosis(0%). Conclusions: IV cangrelor during acute ischemic stroke intervention appears to be safe, with a symptomatic intracranial hemorrhage rate of 6.2%. More research is needed to determine the ideal dosing regimen. [ABSTRACT FROM AUTHOR]

Perioperative lumbar drains commonly are placed for spinal cord protection in patients undergoing endovascular aortic repair. However, the logistics of postoperative neuraxial drain removal is challenging in the presence of systemic antithrombotic therapy. This retrospective case series describes the novel use of cangrelor infusions in this high-risk setting. All lumbar drains were placed preoperatively, and descriptive data were collected including cangrelor infusion duration, time to lumbar drain removal after the infusion discontinuation, clinical course, and overall patient outcomes. There were no neurologic complications associated with lumbar drain insertion or removal, and median time to lumbar drain removal was 150 minutes after cangrelor infusion discontinuation. While further study is needed to validate its efficacy and safety, this case series highlights the promise of cangrelor infusions for systemic antithrombotic therapy in the cardiovascular/surgical intensive care unit. [ABSTRACT FROM AUTHOR]

Tremendous progress has been made in the treatment of ST-segment elevation myocardial infarction (STEMI), the most severe and time-sensitive acute coronary syndrome. Primary percutaneous coronary intervention (PCI) is the preferred method of reperfusion, which has stimulated the development of regional STEMI systems of care with standardized protocols designed to optimize care. However, challenges remain for patients with cardiogenic shock, out-of-hospital cardiac arrest, an expected delay to reperfusion (>120 min), in-hospital STEMI, and more recently, those with Covid-19 infection. Ultimately, the goal is to provide timely reperfusion with primary PCI coupled with the optimal antiplatelet and anticoagulant therapies. We review the challenges and provide insights into the remaining knowledge gaps for contemporary STEMI care.

Ruptured blister type aneurysms are challenging to treat, and the ideal treatment remains debated. Recently, endovascular procedures, particularly flow diversion, gained popularity in treating blister aneurysms; however, the need for dual antiplatelet therapy remains a significant concern. Cangrelor is a novel intravenous P2Y12 platelet receptor antagonist with reversible binding and rapid onset and offset of action. These characteristics are appealing for use in endovascular procedures and may mitigate some concerns associated with other P2Y12 receptor antagonists. In this manuscript, we present the case of a ruptured blister aneurysm to highlight features of pathogenesis relevant to clinical course and patient management, describe current treatment paradigms, and illustrate the benefits of cangrelor in neurosurgical patients. Previously studied exclusively in the cardiac literature, this is one of the first reports of the use of cangrelor in neuro-endovascular procedures. This is important as cangrelor has the potential for improving the safety of endovascular procedures, especially in patients where treatment is associated with high risks of intraprocedural bleeding or other complications that may require further intervention.