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P2Y12

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https://www.readbyqxmd.com/read/28938240/atrial-fibrillation-bleeding-and-coronary-intervention-current-recommendations
#1
Serdar Farhan, Roxana Mehran
The patient population with the need for oral anticoagulation to reduce stroke risk associated with atrial fibrillation (AF) and dual antiplatelet therapy to prevent stent thrombosis and myocardial infarction after percutaneous coronary intervention is increasing. However, patients treated with a triple therapy consisting of oral anticoagulation, aspirin, and a P2Y12 inhibitor have been demonstrated to be at high bleeding risk. The best combination of these agents and the duration of the different therapies are still uncertain...
September 21, 2017: Coronary Artery Disease
https://www.readbyqxmd.com/read/28938069/molecular-recognition-of-agonists-and-antagonists-by-the-nucleotide-activated-g-protein-coupled-p2y2-receptor
#2
Muhammad Rafehi, Alexander Neumann, Younis Baqi, Enas M Malik, Michael Wiese, Vigneshwaran Namasivayam, Christa E Müller
A homology model of the nucleotide-activated P2Y2R was created based on the X-ray structures of the P2Y1 and P2Y12 receptors. Docking studies were performed, and receptor mutants were created to probe the identified binding interactions. Mutation of residues predicted to interact with the ribose (Arg110) and the phosphates of the nucleotide agonists (Arg265, Arg292) or that contribute indirectly to binding (Tyr288) abolished activity. The Y114F, R194A, and F261A mutations led to inactivity of diadenosine tetraphosphate and to a reduced response of UTP...
September 22, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28935927/effects-of-ticagrelor-in-a-mouse-model-of-ischemic-stroke
#3
Keita Yamauchi, Takahiko Imai, Masamitsu Shimazawa, Toru Iwama, Hideaki Hara
Ticagrelor is a direct acting and reversibly binding P2Y12 antagonist approved for the prevention of thromboembolic events. Its potential benefits in ischemic stroke have not been investigated sufficiently. Mice were subjected to 2 hours of transient middle cerebral artery occlusion (MCAO). Mice were orally treated with ticagrelor (10 or 30 mg/kg), aspirin (60 mg/kg), or vehicle at 3 and 24 hours before MCAO and 0 and 6 hours after reperfusion. The infarct volume and neurological deficits 22 hours after reperfusion were evaluated...
September 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28931526/cellubrevin-vesicle-associated-membrane-protein-3-vamp-3-mediated-endocytosis-and-trafficking-regulate-platelet-functions
#4
Meenakshi Banerjee, Smita Joshi, Jinchao Zhang, Carole L Moncman, Shilpi Yadav, Beth A Bouchard, Brian Storrie, Sidney W Whiteheart
Endocytosis is key to fibrinogen (Fg) uptake, trafficking of integrins (αIIbβ3, αvβ3) and purinergic receptors (P2Y1, P2Y12), and thus for normal platelet function. However, the molecular machinery required and possible trafficking routes are still ill-defined. To further identify elements of the platelet endocytic machinery, we examined the role of a vesicle-residing, Soluble N-ethylmaleimide Factor Attachment Protein Receptor (v-SNARE) called Cellubrevin/Vesicle-Associated Membrane Protein-3 (VAMP-3) in platelet function...
September 20, 2017: Blood
https://www.readbyqxmd.com/read/28928091/p2y12-antibody-inhibits-platelet-activity-and-protects-against-thrombogenesis
#5
Nicole R Hensch, Zubair A Karim, Joshua Pineda, Nicole Mercado, Fatima Z Alshbool, Fadi T Khasawneh
Given that platelet hyperactivity is known to give rise to thrombotic disorders, new and/or novel antiplatelet therapies are constantly being developed to add to, or to complement the current arsenal of agents. To this end, adenosine diphosphate (ADP) is an important platelet activator that acts by binding to the G-protein coupled P2Y1 and P2Y12 receptors. Although the contribution of the P2Y12 receptor to the genesis of thrombosis is well established, the parenteral arsenal of drugs targeting this receptor in clinical use is limited to cangrelor...
September 16, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28927294/treatment-of-patients-with-myocardial-infarction-depends-on-history-of-cancer
#6
Sabine Rohrmann, Fabienne Witassek, Paul Erne, Hans Rickli, Dragana Radovanovic
BACKGROUND: Although cancer treatment considerably affects cardiovascular health, little is known about how cancer patients are treated for an acute myocardial infarction. We aimed to investigate whether acute myocardial infarction patients with a history of cancer received the same guideline recommended treatment as those acute myocardial infarction patients without and whether they differ with respect to inhospital outcome. METHODS: All patients with ST-segment elevation myocardial infarction and non-ST-segment elevation myocardial infarction, enrolled between 2002 and mid-2015 in the acute myocardial infarction in Switzerland (AMIS Plus) registry with comorbidity data based on the Charlson comorbidity index were analysed...
September 1, 2017: European Heart Journal. Acute Cardiovascular Care
https://www.readbyqxmd.com/read/28921624/pharmacodynamics-and-pharmacokinetics-of-ticagrelor-versus-clopidogrel-in-patients-with-acute-coronary-syndromes-and-chronic-kidney-disease
#7
Heyang Wang, Jing Qi, Yi Li, Yunbiao Tang, Chao Li, Jing Li, Yaling Han
BACKGROUND: Pivotal clinical trials found ticagrelor reduced ischemic complications to a greater extent than clopidogrel and what is more, the benefit gradually increased with the reduction on creatinine clearance. However, the underlying mechanisms remains poorly explored. METHODS: This is a single-center, prospective, randomized clinical trial involving 60 hospitalized P2Y12 inhibitor naïve patients with CKD (eGFR<60ml/min/1.73m(2) ) and NSTE-ACS. Eligible patients were randomly assigned in a 1:1 ratio to receive ticagrelor(180 mg loading dose, then 90 mg twice daily followed) or clopidogrel(600 mg loading dose, then 75 mg qd followed)...
September 15, 2017: British Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/28921447/structure-pharmacology-and-roles-in-physiology-of-the-p2y12-receptor
#8
Ivar von Kügelgen
P2Y receptors are G-protein-coupled receptors (GPCRs) for extracellular nucleotides. The platelet ADP-receptor which has been denominated P2Y12 receptor is an important target in pharmacotherapy. The receptor couples to Gαi2 mediating an inhibition of cyclic AMP accumulation and additional downstream events including the activation of phosphatidylinositol-3-kinase and Rap1b proteins. The nucleoside analogue ticagrelor and active metabolites of the thienopyridine compounds ticlopidine, clopidogrel and prasugrel block P2Y12 receptors and, thereby, inhibit ADP-induced platelet aggregation...
September 12, 2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28914074/impact-of-test-conditions-on-adp-induced-platelet-function-results-with-the-multiplate-assay-is-further-standardization-required
#9
Döme A Dézsi, Béla Merkely, Judit Skopál, Eszter Barabás, Katalin Várnai, József Faluközy, Gábor Veress, Nasri Alotti, Dániel Aradi
BACKGROUND: Platelet function testing was suggested to help tailor P2Y12-inhibitor therapy; however, the lack of proper standardization is still a limitation. METHODS: In a prospective study, we enrolled clopidogrel-treated and P2Y12-inhibitor naive patients to investigate the influence of (1) time from blood collection, (2) stability of the stored Adenosine diphosphate (ADP) reagent, and (3) the use of enoxaparin on results of the Multiplate assay. Measurements were performed from samples kept for 0, 30, 60, 120, and 240 minutes at room temperature before processing...
January 1, 2017: Journal of Cardiovascular Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/28906404/ticagrelor-induced-life-threatening-bleeding-via-the-cyclosporine-mediated-drug-interaction-a-case-report
#10
Chi Zhang, Long Shen, Min Cui, Xiaoyan Liu, Zhichun Gu
RATIONALE: Ticagrelor has become one of the first-line antiplatelet agents in acute coronary syndrome (ACS) patients recommend by the guideline due to its more potent and predictable antiplatelet effect. However, bleeding is still a severe drug adverse reaction of ticagrelor therapy. We report a first case on ticagrelor-induced life-threatening bleeding via the cyclosporine-mediated drug interaction. PATIENT CONCERNS: A 58-year-old Chinese male who received cyclosporine 200 mg daily 5 years after renal transplantation...
September 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28899427/activation-of-dorsal-horn-cannabinoid-cb2-receptor-suppresses-the-expression-of-p2y12-and-p2y13-receptors-in-neuropathic-pain-rats
#11
Juan Niu, Dujuan Huang, Rui Zhou, MingXia Yue, Tao Xu, Junna Yang, Li He, Hong Tian, XiaoHong Liu, Junwei Zeng
BACKGROUND: More evidence suggests that dorsal spinal cord microglia is an important site contributing to CB2 receptor-mediated analgesia. The upregulation of P2Y12 and P2Y13 purinoceptors in spinal dorsal horn microglia is involved in the development of pain behavior caused by peripheral nerve injury. However, it is not known whether the expression of P2Y12 and P2Y13 receptors at spinal dorsal horn will be influenced after CB2 receptor activation in neuropathic pain rats. METHODS: Chronic constriction injury (CCI) and intrathecal ADPbetaS injection were performed in rats to induce neuropathic pain...
September 12, 2017: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/28898876/filing-sources-after-oral-p2y12-platelet-inhibitors-to-the-food-and-drug-administration-adverse-event-reporting-system-faers
#12
Victor L Serebruany, Vasily Cherepanov, Moo Hyun Kim, Oleg Litvinov, Hector A Cabrera-Fuentes, Thomas A Marciniak
BACKGROUND: The US Food and Drug Administration Adverse Event Reporting System (FAERS) is a global passive surveillance database that relies on voluntary reporting by health care professionals and consumers as well as required mandatory reporting by pharmaceutical manufacturers. However, the initial filers and comparative patterns for oral P2Y12 platelet inhibitor reporting are unknown. We assessed who generated original FAERS reports for clopidogrel, prasugrel, and ticagrelor in 2015...
September 13, 2017: Cardiology
https://www.readbyqxmd.com/read/28883222/temporal-changes-in-platelet-response-in-acute-coronary-syndrome-patients-with-prasugrel-and-clopidogrel-after-stent-implantation
#13
Antonio Tello-Montoliu, José Rivera, Diana Hernández, Ana Silvente, Eva Jover, Ana I Rodriguez, Miriam Quintana, Ana Romero, Esteban Orenes-Piñero, José Miguel Rivera-Caravaca, Francisco Marín, Andrea Veliz, Mariano Valdés
BACKGROUND: Prasugrel has been shown to provide more potency and less variability than clopidogrel, but its potential temporal variability has not been described.Methods and Results:We conducted a prospective open-label study, evaluating platelet reactivity overtime in acute coronary syndrome (ACS) patients on aspirin and clopidogrel (n=60) or prasugrel (n=61), after a percutaneous coronary intervention (PCI). Blood samples were taken at discharge and at 3 and 6 months. Platelet function tests included VerifyNow (VN-P2Y12), and Multiplate Aggregometry (MEA)...
September 6, 2017: Circulation Journal: Official Journal of the Japanese Circulation Society
https://www.readbyqxmd.com/read/28882235/efficacy-and-safety-of-ticagrelor-over%C3%A2-time-in-patients-with-prior-mi-in%C3%A2-pegasus-timi-54
#14
RANDOMIZED CONTROLLED TRIAL
Marc P Bonaca, Robert F Storey, Pierre Theroux, P Gabriel Steg, Deepak L Bhatt, Marc C Cohen, KyungAh Im, Sabina A Murphy, Giulia Magnani, Ton Oude Ophuis, Mikhail Rudah, Alexander Parkhomenko, Daniel Isaza, Gabriel Kamensky, Assen Goudev, Gilles Montalescot, Eva C Jensen, Per Johanson, Eugene Braunwald, Marc S Sabatine
BACKGROUND: Ticagrelor reduces ischemic risk in patients with prior myocardial infarction (MI). It remains unclear whether ischemic risk and the benefits of prolonged P2Y12 inhibition in this population remain consistent over time. OBJECTIVES: The study sought to investigate the pattern of ischemic risk over time and whether the efficacy and safety of ticagrelor were similar early and late after randomization. METHODS: The PEGASUS-TIMI (Prevention of Cardiovascular Events in Patients with Prior Heart Attack Using Ticagrelor Compared to Placebo on a Background of Aspirin-Thrombolysis In Myocardial Infarction) 54 trial randomized patients with prior MI (median 1...
September 12, 2017: Journal of the American College of Cardiology
https://www.readbyqxmd.com/read/28877643/a-case-series-of-18-patients-receiving-ticagrelor-after-carotid-stenting
#15
Elizabeth M Olafson, Jodi R DeGrote, Alexander Drofa, Evgueni Kouznetsov, Michael Manchak, Nathan D Leedahl, David D Leedahl
PURPOSE: Dual antiplatelet therapy (DAPT) with aspirin and a P2Y12 receptor antagonist is often used to prevent thrombotic complications after endovascular stent placement. Most of the published experience surrounding DAPT after carotid stenting is with clopidogrel. Ticagrelor may be a promising alternative, especially in patients who may be considered nonresponders to clopidogrel. However, clinical outcomes utilizing DAPT with ticagrelor in a cohort with carotid stenting is lacking. In this case series, we describe our experience with systematic prescribing of ticagrelor after carotid stent placement in 18 patients...
January 1, 2017: Journal of Pharmacy Practice
https://www.readbyqxmd.com/read/28875498/comparative-study-of-effects-of-vonoprazan-and-esomeprazole-on-anti-platelet-function-of-clopidogrel-or-prasugrel-in-relation-to-cyp2c19-genotype
#16
Takuma Kagami, Mihoko Yamade, Takahiro Suzuki, Takahiro Uotani, Yasushi Hamaya, Moriya Iwaizumi, Satoshi Osawa, Ken Sugimoto, Kazuo Umemura, Hiroaki Miyajima, Takahisa Furuta
Drug-drug interaction between anti-acid and anti-platelet agents has not been fully elucidated. Vonoprazan, a new potassium competitive acid blocker, has been available in Japan. CYP2C19 and CYP3A4 are involved in the metabolism of clopidogrel, prasugrel, esomeprazole and vonoprazan. Using P2Y12 assay, we compared the effects of vonoprazan and esomeprazole on the anti-platelet functions of clopidogrel or prasugrel in 31 healthy Japanese volunteers [14 CYP2C19 homo-extensive (homo-EMs), 9 hetero-extensive (hetero-EMs), and 8 poor metabolizers (PMs)]...
September 5, 2017: Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/28875481/proteinuria-predicts-resistance-to-antiplatelet-therapy-in-ischemic-stroke
#17
Gemlyn George, Nikul Patel, Cecilia Jang, David Wheeler, Sridhara S Yaddanapudi, Jonathan Dissin, Ramani Balu, Janani Rangaswami
The occurrence of a stroke while on antiplatelet agents presents a therapeutic dilemma. One of the main causes for recurrent strokes is antiplatelet resistance more commonly known as high on treatment platelet reactivity (HTPR). Prior studies have established that proteinuria is associated with HTPR following myocardial infarction. Here, we investigated whether dipstick proteinuria correlates with HTPR in patients presenting with stroke. We performed a retrospective cohort analysis of 102 patients admitted for a recurrent ischemic stroke that had either a VerifyNow aspirin or VerifyNow clopidogrel laboratory test performed to assess platelet reactivity...
September 5, 2017: Translational Stroke Research
https://www.readbyqxmd.com/read/28873361/-1-h-nmr-based-pharmacometabolomics-analysis-of-urine-identifies-metabolic-phenotype-of-clopidogrel-high-on-treatment-platelets-reactivity-in-coronary-artery-disease-patients
#18
Arwa M Amin, Lim Sheau Chin, Chin-Hoe Teh, Hamza Mostafa, Dzul Azri Mohamed Noor, Muhamad Ali Sk Abdul Kader, Yuen Kah Hay, Baharudin Ibrahim
Clopidogrel high on treatment platelets reactivity (HTPR) has burdened achieving optimum therapeutic outcome. Although there are known genetic and non-genetic factors associated with clopidogrel HTPR, which explain in part clopidogrel HTPR, yet, great portion remains unknown, often hindering personalizing antiplatelet therapy. Nuclear magnetic resonance ((1)H NMR) pharmacometabolomics analysis is useful technique to phenotype drug response. We investigated using (1)H NMR analysis to phenotype clopidogrel HTPR in urine...
August 19, 2017: Journal of Pharmaceutical and Biomedical Analysis
https://www.readbyqxmd.com/read/28868074/update-on-pharmacological-treatment-of-acute-coronary-syndrome-without-persistent-st-segment-elevation-myocardial-infarction-in-the-elderly
#19
REVIEW
Coşkun Usta, Aslı Bedel
The increase in cardiovascular disease prevalence with ageing has been attributed to several age-related changes such as changes in the vascular wall elasticity, the coagulation and haemostatic system and endothelial dysfunction, among other causes. There is a 50% increased mortality risk per 10-year increase in age starting at 65 years old. Here, we aimed to discuss pharmacological treatment in acute coronary syndrome (ACS) without persistent ST segment elevation myocardial infarction in the elderly. The main aim of ACS treatment in elderly people is at preventing ischemia, myocardial damage and complications...
July 2017: Journal of Geriatric Cardiology: JGC
https://www.readbyqxmd.com/read/28867009/sex-differences-in-the-effect-of-diabetes-mellitus-on-platelet-reactivity-and-coronary-thrombosis-from-the-assessment-of-dual-antiplatelet-therapy-with-drug-eluting-stents-adapt-des-study
#20
Gennaro Giustino, Björn Redfors, Roxana Mehran, Ajay J Kirtane, Usman Baber, Philippe Généreux, Bernhard Witzenbichler, Franz-Josef Neumann, Giora Weisz, Akiko Maehara, Michael J Rinaldi, D Christopher Metzger, Timothy D Henry, David A Cox, Peter L Duffy, Ernest L Mazzaferri, Bruce R Brodie, Thomas D Stuckey, George D Dangas, Sorin J Brener, M Ozgu Ozan, Gregg W Stone
BACKGROUND: Whether the consequences of diabetes mellitus (DM) are worse for women than for men treated with drug-eluting stents (DES) and antiplatelet therapy remain unclear. METHODS: Patients from the Assessment of Dual Antiplatelet Therapy With Drug-Eluting Stents study were stratified according to sex and DM status. We investigated the sex-specific effect of DM on high on-clopidogrel platelet reactivity (HPR), defined as a P2Y12 reaction units ≥208, and the adjusted association of DM on the 2-year risk for coronary thrombotic events (CTE), defined as spontaneous myocardial infarction or definite or probable stent thrombosis...
November 1, 2017: International Journal of Cardiology
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