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Ali Doğan, Serkan Kahraman, Emrah Usta, Emrah Özdemir, Uzay Görmüş, Cavlan Çiftçi
OBJECTIVE: Clopidogrel inhibits platelet aggregation by blockade of platelet adenosine diphosphate (ADP) P2Y12 receptor. Leptin is the obesity gene product, and its serum level increases with obesity. Platelets have leptin receptors on their surfaces. Hyperleptinemia may induce ADP-mediated platelet aggregation. It has been proposed that clopidogrel effect could be diminished with high serum leptin levels. The aim of the present trial was to further investigate the relationship between serum leptin level and clopidogrel resistance...
October 2016: Türk Kardiyoloji Derneği Arşivi: Türk Kardiyoloji Derneğinin Yayın Organıdır
Dimitrios Venetsanos, Sofia Sederholm Lawesson, Eva Swahn, Joakim Alfredsson
AIMS: To provide pharmacodynamic data of crushed and chewed ticagrelor tablets, in comparison with standard integral tablets. METHODS: Ninety nine patients with stable angina were randomly assigned, in a 3:1:1 fashion, to one of the following 180mg ticagrelor loading dose (LD) formulations: A) Integral B) Crushed or C) Chewed tablets. Platelet reactivity (PR) was assessed with VerifyNow before, 20 and 60min after LD. High residual platelet reactivity (HRPR) was defined as >208 P2Y12 reaction units (PRU)...
October 15, 2016: Thrombosis Research
Akil Patel, Timothy R Miller, Ravi Shivashankar, Gaurav Jindal, Dheeraj Gandhi
BACKGROUND AND OBJECTIVE: Acute thrombus formation following aneurysm treatment with the Pipeline embolization device (PED) is a potentially devastating complication that may result in significant thromboembolic sequelae if not promptly treated. We therefore evaluated PED cases complicated by acute thrombus formation at our institution, with an emphasis on identifying early angiographic signs that may portend this event. MATERIALS AND METHODS: We retrospectively identified cases of acute thrombosis following PED placement in 100 consecutive procedures performed at our institution from a prospectively maintained clinical database...
October 21, 2016: Journal of Neurointerventional Surgery
Mengjie Lu, Beili Wu
G protein-coupled receptors (GPCRs) comprise the largest membrane protein family. These receptors sense a variety of signaling molecules, activate multiple intracellular signal pathways, and act as the targets of over 40% of marketed drugs. Recent progress on GPCR structural studies provides invaluable insights into the structure-function relationship of the GPCR superfamily, deepening our understanding about the molecular mechanisms of GPCR signal transduction. Here, we review recent breakthroughs on GPCR structure determination and the structural features of GPCRs, and take the structures of chemokine receptor CCR5 and purinergic receptors P2Y1 R and P2Y12 R as examples to discuss the importance of GPCR structures on functional studies and drug discovery...
October 20, 2016: IUBMB Life
Ali Pourdjabbar, Benjamin Hibbert, Aun-Yeong Chong, Michel R Le May, Marino Labinaz, Trevor Simard, F Daniel Ramirez, Peter Lugomirski, Ronnen Maze, Michael Froeschl, Christopher Glover, Alexander Dick, Jean-Francois Marquis, Jordan Bernick, George Wells, Derek Y F So
Ticagrelor has been endorsed by guidelines as the P2Y12 inhibitor of choice in patients with acute coronary syndrome. Clinically, some patients on ticagrelor will require a switch to clopidogrel; however, the optimal strategy and pharmacodynamics effects of switching remain unknown. Patients with an indication to switch were randomly assigned to either a bolus arm (Clopidogrel 600 mg bolus followed by 75 mg daily, n=30) or a no-bolus arm (Clopidogrel 75 mg daily, n=30). Blood samples were collected at baseline, 12, 24, 48, 54, 60 and 72 hours (h) for assessment of platelet reactivity...
October 20, 2016: Thrombosis and Haemostasis
Kannan Sridharan, Rachna Kataria, Drishti Tolani, Shital Bendkhale, Nithya J Gogtay, Urmila M Thatte
INTRODUCTION: CYP2C19 and P2Y12 polymorphisms have been claimed to alter the pharmacodynamic response to clopidogrel. ABCB1 polymorphism has been associated with the efflux of clopidogrel resulting in decreased bioavailability. Due to paucity of data from Indian population, the present study was undertaken to evaluate the association of genetic polymorphisms of CYP2C19, P2Y12, and ABCB1 with inhibition of platelet aggregation (IPA) by clopidogrel. METHODS: Healthy adults (n = 90) of either gender were administered single dose of 300 mg clopidogrel...
July 2016: Indian Journal of Pharmacology
Raffaele De Caterina, Alessia Delli Veneri
No abstract text is available yet for this article.
October 15, 2016: Portuguese Journal of Cardiology: An Official Journal of the Portuguese Society of Cardiology
Mariana Certal, Adriana Vinhas, Aurora Barros-Barbosa, Fátima Ferreirinha, Maria Adelina Costa, Paulo Correia-de-Sá
Nucleotides released during heart injury affect myocardium electrophysiology and remodelling through P2 purinoceptors activation in cardiac myofibroblasts. ATP and UTP endorse [Ca(2) +]i accumulation and growth of DDR-2/a-SMA-expressing myofibroblasts from adult rat ventricles via P2Y4 and P2Y2 receptors activation, respectively. Ventricular myofibroblasts also express ADP-sensitive P2Yi, P2Yi2 and P2Yi3 receptors as demonstrated by immunofluorescence confocal microscopy and western blot analysis, but little information exists on ADP effects in these cells...
October 18, 2016: Journal of Cellular Physiology
Raghavendra Charan P Makam, Nathaniel Erskine, David D McManus, Darleen Lessard, Joel M Gore, Jorge Yarzebski, Robert J Goldberg
Optimization of medical therapy during discharge planning is vital for improving patient outcomes after hospitalization for acute myocardial infarction (AMI). However, limited information is available about recent trends in the prescribing of evidence-based medical therapies in these patients, especially from a population-based perspective. We describe decade-long trends in the discharge prescribing of aspirin, angiotensin-converting enzyme inhibitors/angiotensin receptor blockers, β blockers, and statins in hospital survivors of AMI...
September 13, 2016: American Journal of Cardiology
Aung Myat, Udaya S Tantry, Jacek Kubica, Paul A Gurbel
Introduction A P2Y12 inhibitor plus aspirin is the most widely used antiplatelet strategy to prevent adverse outcomes in the setting of atherothrombotic vascular disease. Areas Covered A paucity of robust evidence for an optimal dose, gastrointestinal toxicity, ineffectiveness in high-risk patients and interactions with other antiplatelet agents, are major controversies associated with aspirin therapy. Ticagrelor is a reversibly binding oral P2Y12 receptor blocker that mediates potent inhibition of adenosine diphosphate-induced platelet function...
October 14, 2016: Expert Review of Cardiovascular Therapy
Ulrike Flierl, Florian Zauner, Jan-Thorben Sieweke, Christine Berliner, L Christian Napp, Jochen Tillmanns, Johann Bauersachs, Andreas Schäfer
Prasugrel, a potent thienopyridine, achieves stronger inhibition of platelet activation than clopidogrel. However, onset of inhibition is significantly delayed in patients with acute ST-elevation myocardial infarction (STEMI), as haemodynamic instability and morphine application seem to exhibit significant influence. Since rapid onset of effect was demonstrated in non-STEMI patients when prasugrel was administered only after percutaneous coronary intervention (PCI) without increasing cardiovascular event rates we assessed the efficacy of prasugrel loading immediately after PCI for STEMI instead of pre-loading before revascularisation...
October 13, 2016: Thrombosis and Haemostasis
Shinya Ichikawa, Kengo Tsukahara, Yugo Minamimoto, Yuichiro Kimura, Yasushi Matsuzawa, Nobuhiko Maejima, Noriaki Iwahashi, Kiyoshi Hibi, Masami Kosuge, Toshiaki Ebina, Kazuo Kimura
BACKGROUND: Few studies have compared the platelet reactivity of prasugrel and clopidogrel in the acute phase of ST-segment elevation myocardial infarction (STEMI).Methods and Results:Primary percutaneous coronary intervention (PCI) was performed in 78 patients with STEMI within 12 h of onset. Patients were randomly assigned to receive a Japanese standard loading dose of prasugrel 20 mg or clopidogrel 300 mg. Platelet reactivity was serially assessed using the VerifyNow-P2Y12 assay, the results of which were expressed as P2Y12-reaction-units (PRU)...
October 6, 2016: Circulation Journal: Official Journal of the Japanese Circulation Society
Ana Lucrecia Marcano, José Luis Ferreiro
Dual therapy with a P2Y12 receptor antagonist in addition to aspirin is the antiplatelet treatment of choice in patients with acute coronary syndromes or undergoing percutaneous coronary intervention (PCI). However, available oral P2Y12 antagonists have several limitations, mostly due to their pharmacological profile, which can affect outcomes in certain clinical settings. Cangrelor is an intravenous, direct-acting, potent P2Y12 inhibitor with rapid onset and offset of action, which has been recently approved for clinical use in patients undergoing PCI...
November 2016: Current Atherosclerosis Reports
Ajay Yadlapati, Mark Gajjar, Daniel R Schimmel, Mark J Ricciardi, James D Flaherty
ST-elevation myocardial infarction (STEMI), which constitutes nearly 25-40 % of current acute myocardial infarction (AMI) cases, is a medical emergency that requires prompt recognition and treatment. Since the 2013 STEMI practice guidelines, a wealth of additional data that may further advance optimal STEMI practices has emerged. These data highlight the importance of improving patient treatment and transport algorithms for STEMI from non-primary percutaneous coronary intervention (PCI) centers. In addition, a focus on the reduction of total pain-to-balloon (P2B) times rather than simply door-to-balloon (D2B) times may further improve outcomes after primary PCI for STEMI...
October 6, 2016: Internal and Emergency Medicine
Alice Giacomazzi, Maurizio Degan, Stefano Calabria, Alessandra Meneguzzi, Pietro Minuz
Platelet microparticles (PMPs) contribute to thrombogenesis but the effects of antiplatelet drugs on PMPs generation is undefined. The present study investigated the cellular events regulating PMPs shedding, testing in vitro platelet agonists and inhibitors. Platelet-rich plasma from healthy subjects was stimulated with arachidonic acid (AA), U46619, collagen type-I (10 and 1.5 μg/mL), epinephrine, ADP or TRAP-6 and pre-incubated with acetylsalicylic acid (ASA, 100 and 10 μmol/L), SQ-29,548, apyrase, PSB-0739, or eptifibatide...
2016: Frontiers in Pharmacology
Riyaad Aungraheeta, Alexandra Conibear, Mark Butler, Eamonn Kelly, Sven Nylander, Andrew Mumford, Stuart Mundell
Ticagrelor is a potent antagonist of the P2Y12 receptor (P2Y12R) and consequently an inhibitor of platelet activity effective in the treatment of atherothrombosis. Here, we sought to further characterise its molecular mechanism of action. Initial studies showed that ticagrelor promoted a greater inhibition of ADP-induced Ca(2+) release in washed platelets versus other P2Y12R antagonists. This additional effect of ticagrelor beyond P2Y12R antagonism was in part as a consequence of ticagrelor inhibiting the equilibrative nucleoside transporter 1 (ENT1) on platelets, leading to accumulation of extracellular adenosine and activation of Gs-coupled adenosine A2A receptors...
September 30, 2016: Blood
Xin-Gang Li, Ning Ma, Bo Wang, Xiao-Qing Li, Sheng-Hui Mei, Kun Zhao, Yong-Jun Wang, Wei Li, Zhi-Gang Zhao, Shu-Sen Sun, Zhong-Rong Miao
The primary mechanism of clopidogrel resistance is still unclear. We aimed to investigate whether the methylation status of the P2Y12 promoter has effects on platelet function and clinical ischemic events. Patients with ischemic cerebrovascular disease were enrolled into our study. Venous blood samples were drawn for thrombelastograpy (TEG) and active metabolite assay. Patients were divided into a case- or control-group based on the occurrence of ischemic events during a one year follow-up. Two TEG parameters between the case and control groups were statistically significant [ADP inhibition rate (ADP%): P = 0...
September 30, 2016: Scientific Reports
Arman Qamar, Deepak L Bhatt
Thrombotic events such as myocardial infarction or stent thrombosis are the major cause of adverse outcomes in patients undergoing percutaneous coronary intervention (PCI). While current antiplatelet agents, anticoagulants, and PCI techniques have reduced the risk of thrombotic events in PCI-treated patients, a considerable hazard still remains. Cangrelor is an intravenous P2Y12 receptor antagonist that provides a rapid onset and maximal platelet inhibition, which is quickly reversible. In the large-scale CHAMPION PHOENIX trial, cangrelor was shown to reduce ischemic events significantly, including myocardial infarction and stent thrombosis, without increasing the risk of severe bleeding across the full spectrum of patients undergoing PCI, with substantial benefits in all patient subgroups examined...
September 27, 2016: American Journal of Cardiovascular Drugs: Drugs, Devices, and Other Interventions
S T Feng, Y Yan, J Y Fan, X Wang, W Zheng, S P Nie, Sergio Raposeiras-Roubín, Emad Abu-Assi, Jose P Simao Henriques, Fabrizio D Ascenzo, Jorge Saucedo, José R González-Juanatey, Stephen B Wilton, Wouter J Kikkert, Iván Nuñez-Gil, Albert Ariza-Sole, Dimitrios Alexopoulos, Christoph Liebetrau, Tetsuma Kawaji, Claudio Moretti, Zenon Huczek, Toshiharu Fujii, Luis C Correia, Masa-Aki Kawashiri, Sasko Kedev
Objective: The study aimed to analyze the impact of concomitant administration of P2Y12 inhibitors and PPIs on ischemia events in patients with acute coronary syndrome (ACS) after percutaneous coronary intervention (PCI). Methods: We retrospectively analyzed data from a international, multi-center registry between 2003 and 2014 in patients with ACS after PCI, grouped the cohort into patients receiving PPIs or no PPIs and assessed 1-year clinical endpoint (all-cause death/re-infarction). Meanwhile, we grouped the cohort into patients receiving clopidogrel or ticagrelor, and compared the impact of concomitant administration of PPIs and clopidogrel or ticagrelor on 1-year clinical endpoint...
September 6, 2016: Zhonghua Yi Xue za Zhi [Chinese medical journal]
David M Shavelle
No abstract text is available yet for this article.
2016: Journal of the American Heart Association
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