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https://www.readbyqxmd.com/read/28399648/the-highly-selective-caspase-1-inhibitor-vx-765-provides-additive-protection-against-myocardial-infarction-in-rat-hearts-when-combined-with-a-platelet-inhibitor
#1
Xi-Ming Yang, James M Downey, Michael V Cohen, Nicole A Housley, Diego F Alvarez, Jonathon P Audia
Use of ischemic postconditioning and other related cardioprotective interventions to treat patients with acute myocardial infarction (AMI) has failed to improve outcomes in clinical trials. Because P2Y12 inhibitors are themselves postconditioning mimetics, it has been postulated that the loading dose of platelet inhibitors routinely given to patients treated for AMI masks the anti-infarct effect of other intended cardioprotective interventions. To further improve outcomes of patients with AMI, an intervention must be able to provide additive protection in the presence of a P2Y12 platelet inhibitor...
January 1, 2017: Journal of Cardiovascular Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/28382371/characteristics-of-dyspnoea-and-associated-clinical-outcomes-in-the-champion-phoenix-study
#2
William A Parker, Deepak L Bhatt, Jayne Prats, Jonathan R S Day, Philippe Gabriel Steg, Gregg W Stone, Christian W Hamm, Kenneth W Mahaffey, Matthew J Price, C Michael Gibson, Harvey D White, Robert F Storey
Dyspnoea may be induced by some reversibly-binding P2Y12 inhibitors, including cangrelor and ticagrelor. Dyspnoea was not associated with any compromise to the efficacy of ticagrelor in the PLATO study. The CHAMPION PHOENIX study (NCT01156571) compared initial treatment with cangrelor versus initial treatment with clopidogrel in patients undergoing PCI. We investigated the incidence, characteristics, and associated clinical outcomes in patients with dyspnoea in CHAMPION PHOENIX. Adverse events (AEs) of dyspnoea to 48 hours were recorded in patients randomised to cangrelor or clopidogrel in CHAMPION PHOENIX...
April 6, 2017: Thrombosis and Haemostasis
https://www.readbyqxmd.com/read/28379902/cangrelor-a-new-route-for-p2y12-inhibition
#3
Alexandra M Sible, James J Nawarskas
Antiplatelet therapy with a P2Y12 inhibitor is a key component of treatment for patients with acute coronary syndromes undergoing percutaneous coronary intervention. Before the development of cangrelor (Kengreal, The Medicines Company, Parsippany, NJ), only oral P2Y12 inhibitors were available. Cangrelor is a reversible P2Y12 inhibitor that is administered as an intravenous infusion, and its quick onset and offset make it an appealing option for antiplatelet therapy, particularly for patients who are unable to take oral medications...
May 2017: Cardiology in Review
https://www.readbyqxmd.com/read/28345287/contribution-of-platelet-p2y12-receptors-to-chronic-complete-freund-s-adjuvant-induced-inflammatory-pain
#4
K Bekő, B Koványi, F Gölöncsér, G Horváth, Á Dénes, Zs Környei, B Botz, Zs Helyes, C E Müller, B Sperlágh
BACKGROUND: P2Y12 receptor antagonists are widely used in clinical practice to inhibit platelet aggregation. P2Y12 receptors are also known to regulate different forms of pain as well as local and systemic inflammation. However it is not known if platelet P2Y12 receptors contribute to these effects. OBJECTIVES: In this study, we explored the contribution of platelet P2Y12 receptors to chronic inflammatory pain in mice. METHODS: Complete Freund's adjuvant (CFA)-induced chronic inflammatory pain was induced in wild-type and P2ry12 gene-deficient mice (P2ry12-/-), and the potent, direct-acting and reversible P2Y12 receptor antagonists, PSB-0739, and cangrelor were used...
March 27, 2017: Journal of Thrombosis and Haemostasis: JTH
https://www.readbyqxmd.com/read/28335837/potent-p2y12-inhibitors-in-men%C3%A2-versus%C3%A2-women-a%C3%A2-collaborative%C3%A2-meta-analysis%C3%A2-of%C3%A2-randomized%C3%A2-trials
#5
Emily S Lau, Eugene Braunwald, Sabina A Murphy, Stephen D Wiviott, Marc P Bonaca, Steen Husted, Stefan K James, Lars Wallentin, Peter Clemmensen, Matthew T Roe, E Magnus Ohman, Robert A Harrington, Jessica L Mega, Deepak L Bhatt, Marc S Sabatine, Michelle L O'Donoghue
BACKGROUND: Sex-specific differences in response to antiplatelet therapies have been described. Whether women and men derive comparable benefit from intensification of antiplatelet therapy remains uncertain. OBJECTIVES: The study investigated the efficacy and safety of the potent P2Y12 inhibitors in patients with coronary artery disease. METHODS: A collaborative sex-specific meta-analysis was conducted of phase III or IV randomized trials of potent P2Y12 inhibitors, including prasugrel, ticagrelor, and intravenous cangrelor...
March 28, 2017: Journal of the American College of Cardiology
https://www.readbyqxmd.com/read/28296036/targeting-of-c-type-lectin-like-receptor%C3%A2-2-or-p2y12-for-the-prevention-of-platelet-activation-by-immunotherapeutic-cpg-oligodeoxynucleotides
#6
C Delierneux, N Donis, L Servais, O Wéra, C Lecut, M Vandereyken, L Musumeci, S Rahmouni, J Schneider, J A Eble, P Lancellotti, C Oury
Essentials CpG oligodeoxynucleotide (ODN) immuotherapeutics cause undesired platelet activating effects. It is crucial to understand the mechanisms of these effects to identify protective strategies. CpG ODN-induced platelet activation depends on C-type lectin-like receptor 2 (CLEC-2) and P2Y12. Targeting CLEC-2 or P2Y12 fully prevents CpG ODN-induced platelet activation and thrombosis. SUMMARY: Background Synthetic phosphorothioate-modified CpG oligodeoxynucleotides (ODNs) show potent immunostimulatory properties that are widely exploited in clinical trials of anticancer treatment...
March 11, 2017: Journal of Thrombosis and Haemostasis: JTH
https://www.readbyqxmd.com/read/28254957/the-orphan-receptor-gpr17-is-unresponsive-to-uracil-nucleotides-and-cysteinyl-leukotrienes
#7
Katharina Simon, Nicole Merten, Ralf Schroder, Stephanie Hennen, Philip Preis, Nina-Katharina Schmitt, Lucas Peters, Ramona Schrage, Celine Vermeiren, Michel Gillard, Klaus Mohr, Jesus Gomeza, Evi Kostenis
Pairing orphan G protein-coupled receptors (GPCRs) with their cognate endogenous ligands is expected to have a major impact on our understanding of GPCR biology. It follows that reproducibility of orphan receptor ligand pairs should be of fundamental importance to guide meaningful investigations into pharmacology and function of individual receptors. GPR17 is an orphan receptor characterized by some as dualistic uracil-nucleotide/cysteinyl-leukotriene receptor and by others as inactive towards these stimuli altogether...
March 2, 2017: Molecular Pharmacology
https://www.readbyqxmd.com/read/28230176/antithrombotic-therapy-for-patients-with-stemi-undergoing-primary-pci
#8
REVIEW
Francesco Franchi, Fabiana Rollini, Dominick J Angiolillo
Antithrombotic therapy, including antiplatelet and anticoagulant agents, is the cornerstone of pharmacological treatment to optimize clinical outcomes in patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PPCI). Intravenous anticoagulant drugs available for PPCI include the indirect thrombin inhibitors unfractionated heparin and low-molecular-weight heparin, and the direct thrombin inhibitor bivalirudin. Intravenous antiplatelet drugs mainly include glycoprotein IIb/IIIa inhibitors and the P2Y12-receptor inhibitor cangrelor...
February 23, 2017: Nature Reviews. Cardiology
https://www.readbyqxmd.com/read/28223679/synthesis-and-ability-of-new-ligands-for-g-protein-coupled-receptors-17-gpr17
#9
Tongyou Zhuo, Shengxue Zhou, Wei Zhang, Catia Lambertucci, Rosaria Volpini
GPR17 is believed to be a novel target for the development of new therapeutic approaches to human stroke and multiple sclerosis. Hence, the selection of GPR17 ligands may be a potent way to reduce the progression of ischemic damage. New potential ligands for GPR17, mono-, di-, and triphosphate adenosine nucleotides substituted at N6-position with a methyl and a cyclopentyl group were synthesized. The ability of new ligands to bind GPR17 was evaluated using frontal affinity chromatography-mass spectrometry (FAC-MS) method...
February 22, 2017: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
https://www.readbyqxmd.com/read/28219560/a-novel-approach-to-essential-thrombocythemia-and-cardiac-surgery
#10
Bradford B Smith, Gregory A Nuttall, Rajiv K Pruthi, David L Joyce, Matthew S Schuldes, Mark M Smith
Essential thrombocythemia (ET) is a myeloproliferative disorder characterized by persistent thrombocytosis (>450 × 10(9)/L). Patients with ET are at risk for thrombotic or hemorrhagic complications especially during cardiovascular operations. We discuss a patient with ET requiring coronary artery bypass grafting with a presenting platelet count of 1631 × 10(9)/L. Platelet reduction with an intraoperative autologous transfusion technique decreased the platelet count to 758 × 10(9)/L before initiation of cardiopulmonary bypass...
March 2017: Annals of Thoracic Surgery
https://www.readbyqxmd.com/read/28195937/an-updated-protocol-for-evaluating-chest-pain-and-managing-acute-coronary-syndromes
#11
Christopher R Kelly, Ajay J Kirtane, Jennifer Stant, Gregg W Stone, Robert M Minutello, S Chiu Wong, Honeyleen Manuzon, Roxanne Gerow-Smith, Nancy Kelley, LeRoy E Rabbani
Clinical pathways can optimize care both across and within institutions, but regular updates to these pathways based on new clinical trials, professional guidelines, and Food and Drug Administration approvals are essential. Herein we describe the most recent revisions to the New York-Presbyterian Hospital (Columbia University Medical Center and Weill Cornell Medical Center) clinical pathway for acute coronary syndromes and chest pain, which incorporates novel data regarding the timing and administration of P2Y12 inhibition (including the intravenous P2Y12 inhibitor cangrelor) and the appropriateness of prolonged (>1 year) dual antiplatelet therapy for the secondary prevention of ischemic events...
March 2017: Critical Pathways in Cardiology
https://www.readbyqxmd.com/read/28184261/dual-antiplatelet-therapy-and-non-cardiac-surgery-evolving-issues-and-anesthetic-implications
#12
REVIEW
Jong Wook Song, Sarah Soh, Jae-Kwang Shim
Dual antiplatelet therapy (DAPT) consisting of aspirin plus a P2Y12 inhibitor (clopidogrel, prasugrel, or ticagrelor) is imperative for the treatment of acute coronary syndrome, particularly during the re-endothelialization period after percutaneous coronary intervention (PCI). When patients undergo surgery during this period, the consequences of stent thrombosis are far more serious than those of bleeding complications, except in cases of intracranial surgery. The recommendations for perioperative DAPT have changed with emerging evidence regarding the improved efficacy of non-first-generation drug (everolimus, zotarolimus)-eluting stents (DES)...
February 2017: Korean Journal of Anesthesiology
https://www.readbyqxmd.com/read/28104204/randomized-comparison-of-oral-p2y12-receptor-inhibitor-loading-strategies-for-transitioning-from-cangrelor-the-excelsiorload2-trial
#13
Willibald Hochholzer, Pascal Kleiner, Iris Younas, Christian M Valina, Nikolaus Löffelhardt, Michael Amann, Timo Bömicke, Miroslaw Ferenc, Dieter Hauschke, Dietmar Trenk, Franz-Josef Neumann, Christian Stratz
OBJECTIVES: This randomized trial tested whether early loading with prasugrel can provide sufficient platelet inhibition even when given at the start of a 2-h infusion of cangrelor. BACKGROUND: Effective platelet inhibition with intravenous cangrelor reduces the risk of ischemic complications during percutaneous coronary intervention (PCI). Transitioning to oral therapy with clopidogrel or prasugrel is only recommended after discontinuation of cangrelor due to drug interactions...
January 23, 2017: JACC. Cardiovascular Interventions
https://www.readbyqxmd.com/read/28092426/incomplete-reversibility-of-platelet-inhibition-following-prolonged-exposure-to-ticagrelor
#14
A J Gerrits, J A Jakubowski, A Sugidachi, A D Michelson, A L Frelinger
INTRODUCTION: Ticagrelor is described as a reversible P2Y12 antagonist. However, residual platelet inhibition persists after discontinuation of ticagrelor when plasma levels are undetectable. We assessed the reversibility of platelet inhibition by ticagrelor and its active metabolite (T-AM) in comparison with cangrelor and prasugrel's active metabolite (P-AM). METHODS: Whole blood was treated in vitro with ~50% inhibitory concentrations of ticagrelor, T-AM, cangrelor, P-AM and assessed for ADP-stimulated activated GPIIb-IIIa and P-selectin and vasodilator stimulated phosphoprotein (VASP) platelet reactivity index (PRI) before and after 100-fold dilution...
January 16, 2017: Journal of Thrombosis and Haemostasis: JTH
https://www.readbyqxmd.com/read/28089137/a-comparison-of-cangrelor-prasugrel-ticagrelor-and-clopidogrel-in-patients-undergoing-percutaneous-coronary-intervention-a-network-meta-analysis
#15
COMPARATIVE STUDY
Peter C Westman, Michael J Lipinski, Rebecca Torguson, Ron Waksman
BACKGROUND: Newer P2Y12 inhibitors have more rapid onset of platelet inhibition compared with clopidogrel, especially the intravenous P2Y12 inhibitor cangrelor. Direct comparisons between cangrelor and oral P2Y12 inhibitors ticagrelor and prasugrel do not exist. Thus, we performed a network meta-analysis to directly and indirectly compare different P2Y12 inhibitors in patients undergoing percutaneous coronary intervention (PCI). METHODS: MEDLINE/PubMed and ClinicalTrials...
March 2017: Cardiovascular Revascularization Medicine: Including Molecular Interventions
https://www.readbyqxmd.com/read/28058211/organ-transplantation-and-drug-eluting-stents-perioperative-challenges
#16
REVIEW
Aparna Dalal
Patients listed for organ transplant frequently have severe coronary artery disease (CAD), which may be treated with drug eluting stents (DES). Everolimus and zotarolimus eluting stents are commonly used. Newer generation biolimus and novolimus eluting biodegradable stents are becoming increasingly popular. Patients undergoing transplant surgery soon after the placement of DES are at increased risk of stent thrombosis (ST) in the perioperative period. Dual antiplatelet therapy (DAPT) with aspirin and a P2Y12 inhibitor such as clopidogrel, prasugrel and ticagrelor is instated post stenting to decrease the incident of ST...
December 24, 2016: World Journal of Transplantation
https://www.readbyqxmd.com/read/28039321/impact-of-cerebrovascular-events-older-than-one-year-on-ischemic-and-bleeding-outcomes-with-cangrelor-in-percutaneous-coronary-intervention
#17
Neal N Sawlani, Robert A Harrington, Gregg W Stone, Ph Gabriel Steg, C Michael Gibson, Christian W Hamm, Matthew J Price, Jayne Prats, Efthymios N Deliargyris, Kenneth W Mahaffey, Harvey D White, Deepak L Bhatt
BACKGROUND: Cangrelor is a potent intravenous adenosine diphosphate-receptor antagonist that in the CHAMPION trials reduced the 48-hour and 30-day rates of ischemic events during percutaneous coronary intervention without an increase in severe bleeding. METHODS AND RESULTS: CHAMPION PCI (A Clinical Trial to Demonstrate the Efficacy of Cangrelor), CHAMPION PLATFORM (Cangrelor Versus Standard Therapy to Achieve Optimal Management of Platelet Inhibition), and CHAMPION PHOENIX (A Clinical Trial Comparing Cangrelor to Clopidogrel Standard Therapy in Subjects Who Require Percutaneous Coronary Intervention) were 3 randomized, double-blind, double-dummy trials in which cangrelor was compared with clopidogrel during percutaneous coronary intervention...
January 2017: Circulation. Cardiovascular Interventions
https://www.readbyqxmd.com/read/27922911/meta-analysis-of-comparison-of-the-newer-p2y12-inhibitors-oral-preparation-or-intravenous-to-clopidogrel-in-patients-with-acute-coronary-syndrome
#18
Lu Zhang, Jun Lu, Weihua Dong, Huiping Tian, Weiyi Feng, Haisheng You, Hairong He, Jing Ma, Yalin Dong
AIMS: New P2Y12 adenosine diphosphate receptor antagonist that has been used in the treatment of acute coronary syndrome (ACS) with mixed results. This systematic review analyzed and compared the evidence from large, clinical trials regarding the efficacy of clopidogrel relative to that of cangrelor, prasugrel, and ticagrelor in reducing the incidence of cardiovascular events in patients with ACS. METHODS AND RESULTS: This analysis of the findings for comparing newer P2Y12 inhibitors with clopidogrel of 13 clinical trials involving a total of 87,985 patients with ACS ...
November 29, 2016: Journal of Cardiovascular Pharmacology
https://www.readbyqxmd.com/read/27902833/evaluation-of-ischemic-and-bleeding-risks-associated-with-2-parenteral-antiplatelet-strategies-comparing-cangrelor-with-glycoprotein-iib-iiia-inhibitors-an-exploratory-analysis-from-the-champion-trials
#19
Muthiah Vaduganathan, Robert A Harrington, Gregg W Stone, Efthymios N Deliargyris, Ph Gabriel Steg, C Michael Gibson, Christian W Hamm, Matthew J Price, Alberto Menozzi, Jayne Prats, Steven Elkin, Kenneth W Mahaffey, Harvey D White, Deepak L Bhatt
Importance: In the context of contemporary pharmacotherapy, optimal antiplatelet management with percutaneous coronary intervention (PCI) has not been well established. Objective: To compare the ischemic and bleeding risks associated with glycoprotein IIb/IIIa inhibitors (GPIs) and a potent P2Y12 antagonist, cangrelor, in patients undergoing PCI. Design, Setting, and Participants: An exploratory analysis of pooled patient-level data from the 3 phase 3 Cangrelor vs Standard Therapy to Achieve Optimal Management of Platelet Inhibition (CHAMPION PCI, CHAMPION PLATFORM, and CHAMPION PHOENIX) trials of patients undergoing elective or nonelective PCI...
February 1, 2017: JAMA Cardiology
https://www.readbyqxmd.com/read/27886821/cangrelor-pharmacology-clinical-data-and-role-in-percutaneous-coronary-intervention
#20
REVIEW
Matthew J Price
In clinical trials that assessed the safety and efficacy of cangrelor during percutaneous coronary intervention (PCI), cangrelor was administered as a 30-μg/kg bolus followed by a 4-μg/kg/min infusion for at least 2 hours or the duration of the PCI, whichever was longer. Cangrelor is currently indicated as an adjunct to PCI to reduce the risk of myocardial infarction, repeat coronary revascularization, and stent thrombosis in patients who have not been treated with a P2Y12 platelet inhibitor and are not being given a glycoprotein IIb/IIIa inhibitor...
January 2017: Interventional cardiology clinics
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