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P2Y12

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https://www.readbyqxmd.com/read/29791922/p2y12-polymorphisms-and-the-risk-of-adverse-clinical-events-in-patients-treated-with-clopidogrel-a-meta-analysis
#1
Kun Zhao, Ming Yang, Yanxia Lu, Shusen Sun, Wei Li, Xingang Li, Zhigang Zhao
BACKGROUND AND STUDY AIM: Some studies have reported an association between P2Y12 gene polymorphisms and clopidogrel adverse outcomes with inconsistent results. We aimed to explore the relationship between P2Y12 polymorphisms and the risk of adverse clinical events in patients treated with clopidogrel through a meta-analysis. METHODS: A systematic search of PubMed, Web of Science and the Cochrane Library was conducted. Retrieved articles were comprehensively reviewed and eligible studies were included, and the relevant data was extracted for this meta-analysis...
May 23, 2018: Drug Research
https://www.readbyqxmd.com/read/29786541/p2y12-inhibition-in-stemi-early-strong-or-both
#2
Fabio Mangiacapra, Germano Di Sciascio
No abstract text is available yet for this article.
May 20, 2018: EuroIntervention
https://www.readbyqxmd.com/read/29782272/-duration-and-timing-of-initiation-of-therapy-with-platelet-p2y12-inhibitors-in-the-treatment-of-patients-with-acute-coronary-syndrome
#3
S V SHalaev, Z M Safiullina
In recent years, the issues of choice of an agent for dual antiplatelet therapy (DAPT) as well as timing of initiation and duration of DAPT in patients with acute coronary syndrome (ACS) have been actively discussed. In this article we present data of major randomized trials of clopidogrel and novel P2Y12 inhibitors - prasugrel, ticagrelor, cangrelor - assessing strategy of administration of antiaggregants in patients with ACS before coronary angiography / percutaneous coronary intervention. The article also contains analysis of differences between recommendations of the European Society of Cardiology and American College of Cardiology/American Heart Association on therapy with oral P2Y12 inhibitors in the management of patients with ACS...
March 2018: Kardiologiia
https://www.readbyqxmd.com/read/29781069/dual-and-triple-antithrombotic-therapies-current-patterns-of-practice-and-controversies
#4
Mark Crowther, John Eikelboom
Dual antiplatelet therapy (DAPT) has been the cornerstone of antithrombotic management for patients undergoing percutaneous coronary intervention (PCI). Despite low-quality evidence, triple antithrombotic therapy involving acetylsalicylic acid, clopidogrel and warfarin or non-vitamin K antagonist oral anticoagulant (NOAC) has been recommended in patients with concomitant atrial fibrillation undergoing PCI, who require long-term oral anticoagulation, although such strategy is associated with a substantially increased risk of bleeding compared with DAPT...
May 21, 2018: Kardiologia Polska
https://www.readbyqxmd.com/read/29773988/microglia-p2y-13-receptors-prevent-astrocyte-proliferation-mediated-by-p2y-1-receptors
#5
Clara Quintas, Nuno Vale, Jorge Gonçalves, Glória Queiroz
Cerebral inflammation is a common feature of several neurodegenerative diseases that requires a fine interplay between astrocytes and microglia to acquire appropriate phenotypes for an efficient response to neuronal damage. During brain inflammation, ATP is massively released into the extracellular medium and converted into ADP. Both nucleotides acting on P2 receptors, modulate astrogliosis through mechanisms involving microglia-astrocytes communication. In previous studies, primary cultures of astrocytes and co-cultures of astrocytes and microglia were used to investigate the influence of microglia on astroglial proliferation induced by ADPβS, a stable ADP analog...
2018: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/29766335/ticagrelor-versus-clopidogrel-as-part-of-dual-or-triple-antithrombotic-therapy-a-systematic-review-and-meta-analysis
#6
Ioannis Andreou, Alexandros Briasoulis, Christos Pappas, Ignatios Ikonomidis, Dimitrios Alexopoulos
PURPOSE: Clopidogrel is the standard P2Y12 receptor inhibitor used in patients requiring both antiplatelet therapy and oral anticoagulation (OAC). We investigated the safety and efficacy of ticagrelor as an alternative to clopidogrel in patients on OAC. METHODS: A systematic electronic literature search was performed in MEDLINE, EMBASE, and the Cochrane Library for randomised controlled studies that examined the relative safety and efficacy of clopidogrel versus ticagrelor among patients requiring therapy with antiplatelet agents plus OAC...
May 15, 2018: Cardiovascular Drugs and Therapy
https://www.readbyqxmd.com/read/29764713/utility-of-grace-and-acuity-horizons-risk-scores-to-guide-dual-antiplatelet-therapy-in-korean-patients-with-acute-myocardial-infarction-undergoing-drug-eluting-stenting
#7
Doo Sun Sim, Myung Ho Jeong, Hyo Soo Kim, Hyeon Cheol Gwon, Ki Bae Seung, Seung Woon Rha, Shung Chull Chae, Chong Jin Kim, Kwang Soo Cha, Jong Sun Park, Jung Han Yoon, Jei Keon Chae, Seung Jae Joo, Dong Ju Choi, Seung Ho Hur, In Whan Seong, Myeong Chan Cho, Doo Il Kim, Seok Kyu Oh, Tae Hoon Ahn, Jin Yong Hwang
BACKGROUND: Dual antiplatelet therapy (DAPT) is recommended in patients receiving drug-eluting stents (DES). However, bleeding risk should be weighed against ischemic risk. Utility of GRACE risk score and ACUITY-HORIZONS bleeding risk score was assessed in patients with acute myocardial infarction (MI) according to use of P2Y12 blocker. METHODS: From the Korea Acute Myocardial Infarction Registry-National Institute of Health database, 7791 patients with acute MI receiving DES were divided into ticagrelor (n=1554) and clopidogrel (n=6237) groups...
May 12, 2018: Journal of Cardiology
https://www.readbyqxmd.com/read/29754671/rationale-and-design-for-the-vascular-outcomes-study-of-asa-along-with-rivaroxaban-in-endovascular-or-surgical-limb-revascularization-for-peripheral-artery-disease-voyager-pad
#8
Warren H Capell, Marc P Bonaca, Mark R Nehler, Edmond Chen, John M Kittelson, Sonia S Anand, Scott D Berkowitz, Eike Sebastian Debus, Fabrizio Fanelli, Lloyd Haskell, Manesh R Patel, Rupert Bauersachs, William R Hiatt
BACKGROUND: Patients with peripheral artery disease (PAD) undergoing a lower-extremity revascularization are at heightened risk for ischemic cardiac and limb events. Although intensification of antithrombotic therapy after revascularization has demonstrated benefit in coronary disease populations, this approach has not been well studied or shown consistent benefit in PAD. Recent trial evidence demonstrated that a treatment strategy of rivaroxaban added to background antiplatelet therapy reduced ischemic risk in patients following recent acute coronary syndromes, as well as in patients with stable atherosclerotic vascular disease...
May 2018: American Heart Journal
https://www.readbyqxmd.com/read/29748334/genetic-variant-in-human-par-protease-activated-receptor-4-enhances-thrombus-formation-resulting-in-resistance-to-antiplatelet-therapeutics
#9
Benjamin E Tourdot, Hannah Stoveken, Derek Trumbo, Jennifer Yeung, Yogendra Kanthi, Leonard C Edelstein, Paul F Bray, Gregory G Tall, Michael Holinstat
OBJECTIVE: Platelet activation after stimulation of PAR (protease-activated receptor) 4 is heightened in platelets from blacks compared with those from whites. The difference in PAR4 signaling by race is partially explained by a single-nucleotide variant in PAR4 encoding for either an alanine or threonine at amino acid 120 in the second transmembrane domain. The current study sought to determine whether the difference in PAR4 signaling by this PAR4 variant is because of biased Gq signaling and whether the difference in PAR4 activity results in resistance to traditional antiplatelet intervention...
May 10, 2018: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/29748219/frequency-reasons-and-impact-of-premature-ticagrelor-discontinuation-in-patients-undergoing-coronary-revascularization-in-routine-clinical-practice-results-from-the-bern-percutaneous-coronary-intervention-registry
#10
Thomas Zanchin, Fabrice Temperli, Alexios Karagiannis, Christian Zanchin, Markus Räsänen, Konstantinos C Koskinas, Stefan Stortecky, Lukas Hunziker, Fabien Praz, Stefan Blöchlinger, Christina Moro, Aris Moschovitis, Christian Seiler, Michael Billinger, Dik Heg, Thomas Pilgrim, Marco Valgimigli, Stephan Windecker, Lorenz Räber
BACKGROUND: Although ticagrelor has improved clinical outcomes among patients with acute coronary syndrome compared with clopidogrel, adherence to this new antiplatelet agent in real-world practice has not been fully investigated. METHODS AND RESULTS: Between November 2011 and June 2014, 1278 of 4831 consecutive patients (26.5%) undergoing percutaneous coronary intervention at a tertiary care center were treated with ticagrelor. Premature ticagrelor cessation was categorized into (1) change, when ticagrelor was replaced by prasugrel; (2) de-escalation, when ticagrelor was replaced by clopidogrel; and (3) premature discontinuation, when ticagrelor was discontinued without P2Y12 inhibitor replacement...
May 2018: Circulation. Cardiovascular Interventions
https://www.readbyqxmd.com/read/29743380/tailored-adjunctive-cilostazol-therapy-based-on-cyp2c19-genotyping-in-patients-with-acute-myocardial-infarction-the-caldera-gene-study
#11
Koichi Kaikita, Hiromi Yoshimura, Masanobu Ishii, Takashi Kudoh, Yoshihiro Yamada, Eiichiro Yamamoto, Yasuhiro Izumiya, Sunao Kojima, Hideki Shimomura, Ryusuke Tsunoda, Kunihiko Matsui, Hisao Ogawa, Kenichi Tsujita
BACKGROUND: Patients with reduced-function CYP2C19 genotypes on dual antiplatelet therapy (DAPT) with aspirin and clopidogrel show higher clinical risk for acute myocardial infarction (AMI). We investigated the effect of CYP2C19 genotype-tailored adjunctive cilostazol therapy on treatment of AMI.Methods and Results:The study group of 138 patients with suspected AMI were screened for CYP2C19 genotype immediately after percutaneous coronary intervention (PCI) using a SPARTAN RX point-of-care device...
May 8, 2018: Circulation Journal: Official Journal of the Japanese Circulation Society
https://www.readbyqxmd.com/read/29736562/evaluation-of-brain-nuclear-medicine-imaging-tracers-in-a-murine-model-of-sepsis-associated-encephalopathy
#12
Dávid Szöllősi, Nikolett Hegedűs, Dániel S Veres, Ildikó Futó, Ildikó Horváth, Noémi Kovács, Bernadett Martinecz, Ádám Dénes, Daniel Seifert, Ralf Bergmann, Ondřej Lebeda, Zoltán Varga, Zoltán Kaleta, Krisztián Szigeti, Domokos Máthé
PURPOSE: The purpose of this study was to evaluate a set of widely used nuclear medicine imaging agents as possible methods to study the early effects of systemic inflammation on the living brain in a mouse model of sepsis-associated encephalopathy (SAE). The lipopolysaccharide (LPS)-induced murine systemic inflammation model was selected as a model of SAE. PROCEDURES: C57BL/6 mice were used. A multimodal imaging protocol was carried out on each animal 4 h following the intravenous administration of LPS using the following tracers: [99m Tc][2,2-dimethyl-3-[(3E)-3-oxidoiminobutan-2-yl]azanidylpropyl]-[(3E)-3-hydroxyiminobutan-2-yl]azanide ([99m Tc]HMPAO) and ethyl-7-[125 I]iodo-5-methyl-6-oxo-4H-imidazo[1,5-a][1,4]benzodiazepine-3-carboxylate ([125 I]iomazenil) to measure brain perfusion and neuronal damage, respectively; 2-deoxy-2-[18 F]fluoro-D-glucose ([18 F]FDG) to measure cerebral glucose uptake...
May 7, 2018: Molecular Imaging and Biology: MIB: the Official Publication of the Academy of Molecular Imaging
https://www.readbyqxmd.com/read/29731189/potent-effect-of-prasugrel-on-acute-phase-resolution-of-intra-stent-athero-thrombotic-burden-after-percutaneous-intervention-to-acute-coronary-syndrome
#13
Yoshiro Tsukiyama, Amane Kozuki, Toshiro Shinke, Hiromasa Otake, Yoichi Kijima, Tomoya Masano, Ryoji Nagoshi, Hiroyuki Shibata, Ryo Takeshige, Ken-Ichi Yanaka, Junya Shite, Ken-Ichi Hirata
BACKGROUND: Recent studies suggested protruding thrombus and atheroma after stent placement could be a substrate for subsequent adverse ischemic events. Although protruded atherothrombotic burden can be assessed as intra-stent tissue (IST) by optical coherence tomography (OCT), the effects of potent antiplatelet therapy on the acute phase resolution of IST in patients with acute coronary syndrome (ACS) was unknown. METHODS: Ninety-six consecutive ACS patients with multi-vessel disease were enrolled in this prospective registry...
May 3, 2018: Journal of Cardiology
https://www.readbyqxmd.com/read/29730968/is-ticagrelor-worth-its-high-cost-and-side-effects
#14
Raphaëlle-Ashley Guerbaai, Indrajeet Mahata, Sylvestre Maréchaux, Thierry H Le Jemtel, Pierre-Vladimir Ennezat
Ticagrelor is a reversible P2Y12 receptor antagonist that is more potent than clopidogrel. When used in combination with aspirin, it reduces cardiovascular events in patients with acute coronary syndrome. However, unbiased review of 5 randomised controlled trials indicates that although statistically significant, the clinical superiority of ticagrelor over clopidogrel is modest. Thus, identification of patients who benefit the most from ticagrelor is a priority. Besides bleeding issues, ticagrelor can frequently cause bouts of dyspnoea, which requires ticagrelor replacement by another P2Y12 receptor antagonist, with a loading dose...
May 7, 2018: Acta Cardiologica
https://www.readbyqxmd.com/read/29730781/role-of-antiplatelet-therapy-in-the-durability-of-hemodialysis-access
#15
Satinderjit Locham, Robert J Beaulieu, Hanaa Dakour-Aridi, Besma Nejim, Mahmoud B Malas
BACKGROUND: Antiplatelet therapy (APT) is often used on anecdotal grounds to improve vascular access patency. The aim of this study was to assess the role of APT in hemodialysis (HD) patients undergoing arteriovenous fistula (AVF) or graft (AVG) placement. METHODS: All patients in a large HD vascular qualitative initiative database (2011-2017) were included and divided into no antiplatelet therapy (no-APT) vs. any APT [aspirin (ASA) or P2Y12 inhibitors (PI)]. Multivariate [logistic (MLR) and Cox (MCR) regression] analyses were used as appropriate...
May 5, 2018: Journal of Nephrology
https://www.readbyqxmd.com/read/29725296/the-p2y-12-receptor-antagonist-ticagrelor-reduces-lysosomal-ph-and-autofluorescence-in-retinal-pigmented-epithelial-cells-from-the-abca4-mouse-model-of-retinal-degeneration
#16
Wennan Lu, Néstor M Gómez, Jason C Lim, Sonia Guha, Ann O'Brien-Jenkins, Erin E Coffey, Keith E Campagno, Stuart A McCaughey, Alan M Laties, Leif G Carlsson, Claire H Mitchell
The accumulation of partially degraded lipid waste in lysosomal-related organelles may contribute to pathology in many aging diseases. The presence of these lipofuscin granules is particularly evident in the autofluorescent lysosome-associated organelles of the retinal pigmented epithelial (RPE) cells, and may be related to early stages of age-related macular degeneration. While lysosomal enzymes degrade material optimally at acidic pH levels, lysosomal pH is elevated in RPE cells from the ABCA4-/- mouse model of Stargardt's disease, an early onset retinal degeneration...
2018: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/29719963/point-of-care-tests-verifynow-p2y12-and-innovance-pfa-p2y-compared-to-light-transmittance-aggregometry-after-fibrinolysis
#17
Vincent Roule, Pierre Ardouin, Yohan Repessé, Agnès Le Querrec, Katrien Blanchart, Adrien Lemaitre, Rémi Sabatier, Annie Borel-Derlon, Farzin Beygui
Detection of high on-treatment platelet reactivity (HPR) by point-of-care tests has not been validated after successful fibrinolysis for ST-elevation myocardial infarction. We assessed the validity of the point-of-care VerifyNow P2Y12 (VN) and INNOVANCE PFA P2Y (PFA) tests on HPR compared to light transmittance aggregometry (LTA) in these patients. The HPR was identified in 10 (34.5%) patients, 15 (51.7%) patients, and 14 (50%) patients using LTA, VN, and PFA, respectively. Discrepancies were observed between the tests despite significant correlations between platelet reactivity measures by LTA and VN ( r = 0...
January 1, 2018: Clinical and Applied Thrombosis/hemostasis
https://www.readbyqxmd.com/read/29715047/not-all-light-transmission-aggregation-assays-are-created-equal-qualitative-differences-between-light-transmission-and-96-well-plate-aggregometry
#18
Melissa V Chan, Philip D Leadbeater, Steve P Watson, Timothy D Warner
In this short article, submitted as part of the review on platelet function testing, we illustrate the quantitative and qualitative differences between classical light transmission aggregometry (LTA) and 96-well plate aggregometry. We show that responses to platelet agonists and antagonists differ depending upon the method of aggregation testing. For example, in 96-well aggregometry, responses to collagen are strongly inhibited by P2Y12 receptor antagonists while in LTA they are much less affected. Furthermore, we explore the importance of differences in the mechanical environment upon platelet aggregation...
May 1, 2018: Platelets
https://www.readbyqxmd.com/read/29710801/synthesis-of-a-novel-series-of-amino-acid-prodrugs-based-on-thienopyridine-scaffolds-and-evaluation-of-their-antiplatelet-activity
#19
Nan Lu, Lingjun Li, Xuemin Zheng, Shijun Zhang, Yuquan Li, Jing Yuan, Qunchao Wei, Youjun Xu, Fancui Meng
The thienopyridines class of drugs used as P2Y12 receptor antagonists plays a vital role in antiplatelet therapy. To further optimized this compound class, we designed and synthesized a series of amino acid prodrugs of 2-hydroxytetrahydrothienopyridine. All compounds were then evaluated for their inhibitory effect on ADP-induced platelet aggregation in rats and then ED50 and bleeding time of the most potent compounds were compared with commercial drugs. The results showed compound 5c could be a potent and safe candidate for further research...
April 28, 2018: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/29708956/optimal-management-of-cancer-patients-with-acute-coronary-syndrome
#20
Waldemar Banasiak, Robert Zymliński, Anetta Undas
Cancer at various stages and therapy is observed in about 15% of patients with acute coronary syndrome (ACS). Current guidelines for invasive and conservative treatment of ACS cannot be applied to all patients with cancer. The choice of antiplatelet and anticoagulant drugs should be individualized with clopidogrel as a key P2Y12 inhibitor in this population. Major challenges of therapy in patients with ACS and cancer include limitations for the use of the recommended antithrombotic therapy (particularly in case of cancer-related thrombocytopenia or when anticoagulation is needed due to concomitant atrial fibrillation or venous thromboembolism), the management of bleeding complications, eligibility criteria for cancer surgery, and reinitiation of chemotherapy or radiotherapy after ACS...
April 30, 2018: Polish Archives of Internal Medicine
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