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https://www.readbyqxmd.com/read/28102731/microfluidic-whole-blood-testing-of-platelet-response-to-pharmacological-agents
#1
Ruizhi Li, Tilo Grosser, Scott L Diamond
Platelets present a number of intracellular and transmembrane targets subject to pharmacological modulation, either for cardiovascular disease reduction or as an unintended drug response. Microfluidic devices allow human blood to clot on a defined surface under controlled hemodynamic and pharmacological conditions. The potencies of a number of antiplatelet and anticancer drugs have been tested with respect to platelet deposition on collagen under flow. Inhibitors of cyclooxygenase-1 (COX-1) reduce platelet deposition, either when added ex vivo to blood or ingested orally by patients prior to testing...
January 19, 2017: Platelets
https://www.readbyqxmd.com/read/28097533/long-term-use-of-ticagrelor-in-patients-with-coronary-artery-disease
#2
REVIEW
Sara Ariotti, Giuseppe Gargiulo, Marco Valgimigli
PURPOSE OF REVIEW: This review aims to summarize and discuss safety and effectiveness of the long-term use of ticagrelor in patients with coronary artery disease (CAD). RECENT FINDINGS: Ticagrelor is an orally administered, direct, and reversible inhibitor of the P2Y12-platelet receptor. Long-term use of ticagrelor in patients with previous myocardial infarction (MI) has been investigated in the PEGASUS-TIMI-54 trial. Overall, 21,162 patients with a spontaneous MI 1 to 3 years before randomization were randomly assigned to ticagrelor 90 mg bid, ticagrelor 60 mg bid, or placebo...
January 2017: Current Cardiology Reports
https://www.readbyqxmd.com/read/28095326/additive-antithrombotic-effect-of-asp6537-a-selective-cyclooxygenase-cox-1-inhibitor-in-combination-with-clopidogrel-in-guinea-pigs
#3
Chinatsu Sakata, Ken-Ichi Suzuki, Yoshiaki Morita, Tomihisa Kawasaki
Clopidogrel (Plavix(®), Sanofi-Aventis), the adenosine diphosphate P2Y12 receptor antagonist, is reported to be effective in the prevention of cardiovascular events and is often used in combination with aspirin, particularly in high-risk patients. ASP6537 is a reversible cyclooxygenase (COX)-1 inhibitor that is under investigation as an anti-platelet agent. First, we investigated the reversibility of the antiplatelet effect of ASP6537 and its interaction with ibuprofen to compare the usability of ASP6537 with that of aspirin...
January 14, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28092426/incomplete-reversibility-of-platelet-inhibition-following-prolonged-exposure-to-ticagrelor
#4
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/28091702/platelet-receptor-gene-p2y12-p2y1-and-platelet-glycoprotein-gene-gpiiia-polymorphisms-are-associated-with-antiplatelet-drug-responsiveness-and-clinical-outcomes-after-acute-minor-ischemic-stroke
#5
Xingyang Yi, Qiang Zhou, Chun Wang, Jing Lin, Ping Liu, Cheng Fu
PURPOSE: Patients with minor ischemic stroke (MIS) are at high risk of recurrent ischemic stroke (RIS). The aim of this study was to evaluate the effects of platelet receptor gene (P2Y12, P2Y1) and glycoprotein gene (GPIIIa) polymorphisms, as well as their interactions, on antiplatelet drug responsiveness and clinical outcomes in patients with acute MIS. METHODS: We prospectively enrolled 426 patients with acute MIS who had been receiving combined aspirin and clopidogrel treatment for at least 3 months...
January 13, 2017: European Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/28089137/a-comparison-of-cangrelor-prasugrel-ticagrelor-and-clopidogrel-in-patients-undergoing-percutaneous-coronary-intervention-a-network-meta-analysis
#6
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...
October 21, 2016: Cardiovascular Revascularization Medicine: Including Molecular Interventions
https://www.readbyqxmd.com/read/28068952/interaction-among-cox-2-p2y1-and-gpiiia-gene-variants-is-associated-with-aspirin-resistance-and-early-neurological-deterioration-in-chinese-stroke-patients
#7
Xingyang Yi, Chun Wang, Qiang Zhou, Jing Lin
BACKGROUND: The effect of genetic variants on aspirin resistance (AR) remains controversial. We sought to assess the association of genetic variants with AR and early clinical outcomes in patients with acute ischemic stroke (IS). METHODS: A total of 850 acute IS patients were consecutively enrolled. Platelet aggregation was measured before and after a 7-10 day aspirin treatment. The sequences of 14 variants of COX-1, COX-2, GPIb, GPIIIa, P2Y1 and P2Y12 were determined using matrix-assisted laser desorption/ionization time of flight mass spectrometry...
January 9, 2017: BMC Neurology
https://www.readbyqxmd.com/read/28065908/ticagrelor-but-not-clopidogrel-active-metabolite-displays-antithrombotic-properties-in-the-left-atrial-endocardium
#8
Martin F Reiner, Alexander Breitenstein, Erik W Holy, Martina Glanzmann, Heidi Amstalden, Simon F Stämpfli, Nicole R Bonetti, Volkmar Falk, Stephan Keller, Gianluigi Savarese, Stefano Benussi, Francesco Maisano, Thomas F Lüscher, Jürg H Beer, Jan Steffel, Giovanni G Camici
AIMS: Oral anticoagulation is considered standard therapy for stroke prevention in atrial fibrillation (AF). Endocardial activation triggers expression of pro-thrombotic mediators including tissue factor (TF) and plasminogen activator inhibitor-1 (PAI-1), and contributes to thrombus formation in the left atrial appendage (LAA) of AF patients. Recently, pleiotropic effects of specific P2Y12 receptor antagonists were demonstrated; however, whether these drugs possess antithrombotic effects on LAA endocardial cells currently remains unknown...
January 8, 2017: European Heart Journal
https://www.readbyqxmd.com/read/28065907/platelet-reactivity-in-human-immunodeficiency-virus-infected-patients-on-dual-antiplatelet-therapy-for-an-acute-coronary-syndrome-the-evere2st-hiv-study
#9
Marie Hauguel-Moreau, Franck Boccara, Anders Boyd, Joe-Elie Salem, Delphine Brugier, Angélique Curjol, Jean-Sébastien Hulot, Mathieu Kerneis, Sophie Galier, Ariel Cohen, Gilles Montalescot, Jean-Philippe Collet, Johanne Silvain
AIM: To explore platelet reactivity on dual antiplatelet therapy (DAPT) of acute coronary syndrome (ACS) patients infected with HIV. METHODS AND RESULTS: Acute coronary syndrome patients infected with HIV (n = 80) were matched to ACS patients without HIV (n = 160) on age, sex, diabetes, and DAPT (aspirin 100%, clopidogrel 68%, prasugrel 31%, ticagrelor 1%). Platelet reactivity was evaluated after ACS (>30 days) by measuring residual platelet aggregation (RPA) to aspirin and to P2Y12 inhibitors with light transmission aggregometry (LTA), VerifyNow aspirin assay (ARU), and P2Y12 assay (PRU) and with the VASP platelet reactivity index (VASP-PRI)...
January 8, 2017: European Heart Journal
https://www.readbyqxmd.com/read/28062501/p2y12-promotes-migration-of-vascular-smooth-muscle-cells-through-cofilin-dephosphorylation-during-atherogenesis
#10
Xuan Niu, Shu-Lan Pi, Suraj Baral, Yuan-Peng Xia, Quan-Wei He, Ya-Nan Li, Hui-Juan Jin, Man Li, Meng-Die Wang, Ling Mao, Bo Hu
OBJECTIVE: P2Y12 is a well-recognized receptor expressed on platelets and the target of thienopyridine-type antiplatelet drugs. However, recent evidence suggests that P2Y12 expressed in vessel wall plays a role in atherogenesis, but the mechanisms remain elusive. In this study, we examined the molecular mechanisms of how vessel wall P2Y12 mediates vascular smooth muscle cells (VSMCs) migration and promotes the progression of atherosclerosis. APPROACH AND RESULTS: Using a high-fat diet-fed ApoE knockout mice model, we found that the expression of P2Y12 in VSMCs increased in a time-dependent manner and had a linear relationship with the plaque area...
January 5, 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/28062136/p2y12-receptor-inhibition-with-prasugrel-and-ticagrelor-in-stemi-patients-after-fibrinolytic-therapy-analysis-from-the-sampa-randomized-trial
#11
Leonardo de F C Guimarães, Philippe Généreux, Diego Silveira, Antonio Eduardo Pesaro, Felipe Falcão, Bruno Robalinho C Barbosa, Cristiano Freitas de Souza, Francisco A H Fonseca, Cláudia Maria Rodrigues Alves, Antônio Carlos de Camargo Carvalho, Gregg W Stone, Adriano Caixeta
BACKGROUND: A pharmacodynamic comparison between ticagrelor and prasugrel after fibrinolytic therapy has not yet been performed. METHODS: In the single-center SAMPA trial, 50 consecutive STEMI patients previously treated with clopidogrel and undergoing a pharmacoinvasive strategy were randomized to either a ticagrelor (n=25) 180mg loading dose followed by 90mg bid, or a prasugrel (n=25) 60mg loading dose followed by 10mg/day, initiated after fibrinolytic therapy but before angiography...
December 27, 2016: International Journal of Cardiology
https://www.readbyqxmd.com/read/28060719/temporal-quantitative-phosphoproteomics-of-adp-stimulation-reveals-novel-central-nodes-in-platelet-activation-and-inhibition
#12
Florian Beck, Jörg Geiger, Stepan Gambaryan, Fiorella A Solari, Margherita Dell'Aica, Stefan Loroch, Nadine Mattheij, Igor Mindukshev, Oliver Pötz, Kerstin Jurk, Julia M Burkhart, Christian Fufezan, Johan W M Heemskerk, Ulrich Walter, René P Zahedi, Albert Sickmann
ADP enhances platelet activation by virtually any other stimulant to complete aggregation. It binds specifically to the G-protein coupled membrane receptors P2Y1 and P2Y12, stimulating intracellular signaling cascades leading to integrin αIIbβ3 activation, a process that is antagonized by endothelial prostacyclin. P2Y12 inhibitors are among the most successful anti-platelet drugs, however, show remarkable variability in efficacy. We reasoned whether a more detailed molecular understanding of ADP-induced protein phosphorylation could identify (i) critical hubs in platelet signaling towards aggregation, and (ii) novel molecular targets for anti-platelet treatment strategies...
November 9, 2016: Blood
https://www.readbyqxmd.com/read/28058211/organ-transplantation-and-drug-eluting-stents-perioperative-challenges
#13
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/28057794/purinergic-signaling-in-the-cardiovascular-system
#14
REVIEW
Geoffrey Burnstock
There is nervous control of the heart by ATP as a cotransmitter in sympathetic, parasympathetic, and sensory-motor nerves, as well as in intracardiac neurons. Centers in the brain control heart activities and vagal cardiovascular reflexes involve purines. Adenine nucleotides and nucleosides act on purinoceptors on cardiomyocytes, AV and SA nodes, cardiac fibroblasts, and coronary blood vessels. Vascular tone is controlled by a dual mechanism. ATP, released from perivascular sympathetic nerves, causes vasoconstriction largely via P2X1 receptors...
January 6, 2017: Circulation Research
https://www.readbyqxmd.com/read/28056847/impact-of-diabetes-and-hypertension-on-cardiovascular-outcomes-in-patients-with-coronary-artery-disease-receiving-percutaneous-coronary-intervention
#15
Mao-Jen Lin, Chun-Yu Chen, Hau-De Lin, Han-Ping Wu
BACKGROUND: Percutaneous coronary intervention (PCI) is a necessary procedure commonly performed for patients with coronary artery disease (CAD). However, the impact of diabetes and hypertension on long-term outcomes of patients after receiving PCI has not yet been determined. METHODS: The data of 1234 patients who received PCI were collected prospectively, and patients were divided into four groups, including patients with and without DM and those with either DM or hypertension alone...
January 5, 2017: BMC Cardiovascular Disorders
https://www.readbyqxmd.com/read/28056791/ticagrelor-induced-systemic-inflammatory-response-syndrome
#16
Philipp Krisai, Manuel Haschke, Peter T Buser, Christian Mueller
BACKGROUND: Ticagrelor is a reversible and direct-acting oral antagonist of the adenosine diphosphate receptor P2Y12. Possible adenosine-mediated effects of ticagrelor on inflammation are complex and incompletely understood. To our knowledge, ticagrelor-induced systemic inflammatory response syndrome (SIRS) has not yet been described. CASE PRESENTATION: We report the case of an 84 years old patient presenting with SIRS subsequent to initiation of ticagrelor after implantation of two drug eluting stents...
January 6, 2017: BMC Cardiovascular Disorders
https://www.readbyqxmd.com/read/28049954/no-effect-of-slco1b1-and-cyp3a4-5-polymorphisms-on-the-pharmacokinetics-and-pharmacodynamics-of-ticagrelor-in-healthy-chinese-male-subjects
#17
Mupeng Li, Yaodong Hu, Huilan Li, Zhipeng Wen, Xiaolei Hu, Daoyu Zhang, Yanjiao Zhang, Jian Xiao, Jie Tang, Xiaoping Chen
Ticagrelor is a direct-acting P2Y12 receptor antagonist. It is rapidly absorbed and partly metabolized to the active metabolite AR-C124910XX by CYP3A4 and CYP3A5. Three genetic loci (SLCO1B1, CYP3A4, and UGT2B7) were reported to affect ticagrelor pharmacokinetics. This study aimed to investigate the possible effects of SLCO1B1 and CYP3A4/5 genetic polymorphisms on the pharmacokinetics and pharmacodynamics of ticagrelor in healthy Chinese male volunteers. Eighteen healthy male volunteers who participated in pharmacogenetics study of ticagrelor were genotyped for SLCO1B1 rs113681054, SLCO1B1*5 (rs4149056), CYP3A4*1G (rs2242480), and CYP3A5*3 (rs776746)...
2017: Biological & Pharmaceutical Bulletin
https://www.readbyqxmd.com/read/28045759/efficacy-and-safety-of-novel-oral-p2y12-receptor-inhibitors-in-st-segment-elevation-myocardial-infarction-patients-undergoing-pci-a-systematic-review-and-meta-analysis
#18
Jianjun Sun, Qian Xiang, Chao Li, Zining Wang, Kun Hu, Qiufen Xie, Yimin Cui
The efficacy and safety of novel oral P2Y12 receptor inhibitors (prasugrel and ticagrelor) are subjects of contention in ST-segment elevation myocardial infarction (STEMI) patients undergoing PCI, the optimal duration of therapy remains uncertain. We searched PubMed, Embase, Cochrane Library, CNKI, VIP, and WanFang Data to identify randomized controlled trials comparing novel oral P2Y12 receptor inhibitors to clopidogrel in STEMI patients undergoing PCI until February 2016. The primary efficacy and safety endpoint were all-cause mortality and major/minor bleeding...
January 3, 2017: Journal of Cardiovascular Pharmacology
https://www.readbyqxmd.com/read/28041804/endovascular-treatment-of-the-common-femoral-artery-in-the-vascular-quality-initiative
#19
Jeffrey J Siracuse, Kathryn Van Orden, Jeffrey A Kalish, Mohammad H Eslami, Marc L Schermerhorn, Virendra I Patel, Denis Rybin, Alik Farber
OBJECTIVE: Endovascular interventions of the common femoral (CFA) and deep (DFA) femoral arteries are becoming more common. However, there is very little published data for guidance. Our objective was to analyze practice patterns and outcomes from these interventions. METHODS: The Vascular Quality Initiative (2010-2015) was queried for all endovascular interventions of the CFA and DFA. Cases that were emergent or for acute limb ischemia were excluded. Those with isolated CFA with or without DFA treatment were analyzed...
December 29, 2016: Journal of Vascular Surgery
https://www.readbyqxmd.com/read/28028830/retrospective-evaluation-of-postoperative-adverse-drug-events-in-patients-receiving-rivaroxaban-following-major-orthopedic-surgery-compared-to-standard-therapy-in-a-community-hospital
#20
Nicole E Cieri, Kristen Kusmierski, Cynthia Lackie, August Van Opdorp, Amany Hassan
STUDY OBJECTIVES: To evaluate the occurrence of bleeding and venous thromboembolic (VTE) events in patients receiving rivaroxaban, warfarin, or warfarin with the addition of enoxaparin during the immediate post-operative period following major orthopedic surgery. METHODS: Patients older than 18 years who received at least one dose of rivaroxaban the morning following surgery, adjusted dose warfarin, or adjusted dose warfarin with the addition of enoxaparin for VTE prophylaxis following major orthopedic surgery between October 1, 2011 and February 28, 2015 were included...
December 27, 2016: Pharmacotherapy
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