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Antiplatelet therapy is mandatory for prevention of thrombotic events in patients with a recent history of acute coronary syndromes and/or percutaneous coronary interventions. However, if an urgent surgery is required during antiplatelet therapy, a compromise between the ischemic/thrombotic and hemorrhagic risk has to be reached. Different bridging schemes are reported in the literature, but there is no clear consensus on the optimal treatment strategy in terms of efficacy and safety. Although some indications about the perioperative management of antiplatelet therapy regarding specific surgical specializations are available, balancing the thrombotic and hemorrhagic risk on an individual basis, no evidence referring to neurosurgical or neuro-oncologic procedures is reported. Herein, we present our preliminary experience in the perioperative management of a patient who underwent a neurosurgical procedure for the resection of a primary malignant brain tumor using an intravenous P2Y 12 inhibitor (cangrelor) as bridging therapy after a recent acute myocardial infarction treated with primary percutaneous coronary intervention and stenting. The oral P2Y 12 inhibitor (clopidogrel) was withdrawn 5 days prior to the surgical procedure and continuous infusion of cangrelor was started 3 days before the surgery at a dose of 0.75 μg/kg/min. Cangrelor was discontinued 2 hours before surgery and resumed 72 hours after tumor resection for further 60 hours. Neither cangrelor-related bleeding nor cardiac ischemic events were observed in the perioperative period and the following 90 days, supporting data regarding the feasibility and safety of this bridging scheme. Further studies are needed to confirm our promising results. [ABSTRACT FROM AUTHOR]

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]

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.