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P2Y12

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https://www.readbyqxmd.com/read/28733972/expression-and-function-of-the-metabotropic-purinergic-p2y-receptor-family-in-experimental-seizure-models-and-patients-with-drug-refractory-epilepsy
#1
Mariana Alves, Rosa Gomez-Villafuertes, Norman Delanty, Michael A Farrell, Donncha F O'Brien, Maria Teresa Miras-Portugal, Miguel Diaz Hernandez, David C Henshall, Tobias Engel
OBJECTIVE: ATP is released into the extracellular space during pathologic processes including increased neuronal firing. Once released, ATP acts on P2 receptors including ionotropic P2X and metabotropic P2Y receptors, resulting in changes to glial function and neuronal network excitability. Evidence suggests an involvement of P2Y receptors in the pathogenesis of epilepsy, but there has been no systematic effort to characterize the expression and function of the P2Y receptor family during seizures and in experimental and human epilepsy...
July 21, 2017: Epilepsia
https://www.readbyqxmd.com/read/28730406/benefits-and-risks-of-p2y12-inhibitor-preloading-in-patients-with-acute-coronary-syndrome-and-stable-angina
#2
REVIEW
Taylor C Bazemore, Michael G Nanna, Sunil V Rao
Treatment with P2Y12 inhibitors is an integral part of the standard of care for patients undergoing percutaneous coronary intervention. However, the most appropriate timing for P2Y12 inhibitor administration remains unclear, and the value of "preloading" with P2Y12 inhibitors prior to cardiac catheterization is controversial. While pre-catheterization treatment with P2Y12 inhibitors is performed with the goal of decreasing adverse cardiovascular events, this potential benefit must be weighed against the increased risk of bleeding complications and operative delay if coronary artery bypass graft surgery is indicated...
July 20, 2017: Journal of Thrombosis and Thrombolysis
https://www.readbyqxmd.com/read/28727707/continuing-anti-thrombotic-medication-during-low-to-intermediate-risk-spinal-procedures-a-retrospective-evaluation
#3
Noud van Helmond, Wesley Day, Kenneth B Chapman
BACKGROUND: The current American Society of Regional Anesthesia (ASRA) guidelines recommend discontinuing anti-thrombotic therapy prior to any interventional spine procedures to decrease the incidence of bleeding complications. However, discontinuing anti-thrombotics may pose considerable danger in terms of cerebrovascular and cardiovascular events. Recent evidence suggests that some spinal interventions may still be performed safely with anti-thrombotics on board and some practitioners thus elect to continue certain anti-thrombotics for these procedures...
July 2017: Pain Physician
https://www.readbyqxmd.com/read/28727490/comparison-of-the-release-of-micrornas-and-extracellular-vesicles-from-platelets-in-response-to-different-agonists
#4
Ashley R Ambrose, Mohammed A Alsahli, Sameer A Kurmani, Alison H Goodall
On activation platelets release microRNAs and extracellular vesicles (EV) into circulation. The release of EV from platelets has been shown to be dependent on the agonist; in this study, we investigated whether the microRNA profile or EV released from platelets was also agonist specific. Washed platelets from healthy subjects were maximally stimulated with agonists specific for the receptors for collagen (Glycoprotein VI (GPVI)), thrombin (PAR1/PAR4), or ADP (P2Y1/P2Y12) with/without inhibiting secondary mediators, using aspirin to block cyclooxygenase-1 and apyrase to remove ADP...
July 20, 2017: Platelets
https://www.readbyqxmd.com/read/28727479/extracellular-chloride-is-required-for-efficient-platelet-aggregation
#5
Kirk A Taylor, Darren G S Wilson, Matthew T Harper, Nicholas Pugh
Anion channels perform a diverse range of functions and have been implicated in ATP release, volume regulation, and phosphatidylserine exposure. Platelets have been shown to express several anion channels but their function is incompletely understood. Due to a paucity of specific pharmacological blockers, we investigated the effect of extracellular chloride substitution on platelet activation using aggregometry and flow cytometry. In the absence of extracellular chloride, we observed a modest reduction of the maximum aggregation response to thrombin or collagen-related peptide...
July 20, 2017: Platelets
https://www.readbyqxmd.com/read/28727358/-antiplatelet-therapy-in-secondary-stroke-prevention
#6
Lorenz Hirt, Emmanuel Carrera
New studies have refined the role of antiplatelet therapy in secondary prevention after noncardioembolic strokes. The first line antiplatelet therapy remains Aspirin. Clopidogrel and the combination aspirine plus dipyridamole are suitable alternatives with a slightly better protection. Ticagrelor, a reversible P2Y12 receptor inhibitor used in cardiology, has not demonstrated its superiority to Aspirin. Early after stroke, a double antiplatelet therapy combining Aspirin and clopidogrel is increasingly administered as a recent study demonstrated a decrease in the incidence of cerebrovascular events after a minor stroke or high-risk TIA...
April 26, 2017: Revue Médicale Suisse
https://www.readbyqxmd.com/read/28717113/add-on-antiplatelet-effects-of-eicosapentaenoic-acid-with-tailored-dose-setting-in-patients-on-dual-antiplatelet-therapy
#7
Naoyoshi Hosogoe, Shuichi Ishikawa, Naoyuki Yokoyama, Ken Kozuma, Takaaki Isshiki
The aim of this study was to investigate the antiplatelet effects of eicosapentaenoic acid (EPA) at a sufficient dose following coronary stent implantation. Thirty-one patients on dual antiplatelet therapy with aspirin and clopidogrel were treated with highly purified EPA-E (Epadel(®)) for 12 weeks. Based on our previous study, patients with a high baseline EPA/arachidonic acid (AA) ratio (≥ 0.37; n = 11) were given a standard dose (1800 mg daily) of EPA-E, whereas those with a low EPA/AA ratio (< 0.37; n = 20) were given a high dose (2700 mg daily) to reach the target value of > 0...
July 14, 2017: International Heart Journal
https://www.readbyqxmd.com/read/28701676/efficacy-and-safety-of-triple-therapy-and-dual-therapy-with-direct-oral-anticoagulants-compared-to-warfarin
#8
Hideo Amano, Daiga Saito, Takayuki Yabe, Ryo Okubo, Mikihito Toda, Takanori Ikeda
The efficacy and safety of direct oral anticoagulants (DOAC) with antiplatelet therapy compared to warfarin are unclear. The subjects were 280 patients who received antiplatelet therapy with oral anticoagulation (OAC) for the treatment of or protection from thromboembolism between January 2012 and September 2015. Among the 280 subjects, 79 (28.2%) received dual therapy (OAC plus aspirin or P2Y12 inhibitor) with DOAC, 75 (26.8%) dual therapy with warfarin, 46 (16.4%) triple therapy (OAC plus aspirin and P2Y12 inhibitor) with DOAC, and 80 (28...
July 13, 2017: International Heart Journal
https://www.readbyqxmd.com/read/28700987/impact-of-intravenous-p2y12-receptor-inhibition-with-cangrelor-in-patients-presenting-with-acute-coronary-syndrome-and-cardiogenic-shock-a-case-series
#9
Michal Droppa, Oliver Borst, Dominik Rath, Karin Müller, Meinrad Gawaz, Deepak L Bhatt, Tobia Geisler
BACKGROUND/AIMS: Patients with acute coronary syndromes (ACS) presenting with cardiogenic shock (CS) are at particular risk for death and adverse cardiac events. Impaired effects and absorption of oral P2Y12-receptor inhibitors due to decreased organ hypoperfusion or hypothermia and challenges regarding oral administration contribute to this risk. We report a single center experience regarding the use of intravenous P2Y12-receptor inhibitor cangrelor in patients with CS treated with percutaneous coronary intervention (PCI)...
July 13, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28692111/a-randomised-trial-on-the-effect-of-anti-platelet-therapy-on-the-systemic-inflammatory-response-in-human-endotoxaemia
#10
Dorien Kiers, Wouter A van der Heijden, Lisa van Ede, Jelle Gerretsen, Quirijn de Mast, André J van der Ven, Saloua El Messaoudi, Gerard A Rongen, Marc Gomes, Matthijs Kox, Peter Pickkers, Niels P Riksen
The use of acetylsalicylic acid (ASA) is associated with improved outcome in patients with sepsis, and P2Y12 inhibitors have been suggested to also have immunomodulatory effects. Therefore, we evaluated the effects of clinically relevant combinations of antiplatelet therapy on the immune response in experimental endotoxaemia in humans in vivo. Forty healthy subjects were randomised to seven days of placebo, placebo with ASA, ticagrelor and ASA, or clopidogrel and ASA treatment. Systemic inflammation was elicited at day seven by intravenous administration of Escherichia coli endotoxin...
July 6, 2017: Thrombosis and Haemostasis
https://www.readbyqxmd.com/read/28690699/feasibility-of-clinical-pharmacist-led-cyp2c19-genotyping-for-patients-receiving-non-emergent-cardiac-catheterization-in-an-integrated-health-system
#11
Samuel G Johnson, Paul B Shaw, Thomas Delate, Deanna L Kurz, Dylon Gregg, John C Darnell, Christina L Aquilante
OBJECTIVE: To assess the feasibility of clinical pharmacist-led CYP2C19 genotype-guided P2Y12 inhibitor antiplatelet drug therapy recommendations to cardiologists in an outpatient cardiology practice. METHODS: This was a prospective, open-labeled, single-arm study conducted in an integrated healthcare delivery system between March 1, 2013 and January 23, 2014. Patients requiring non-emergent cardiac catheterization were included. A clinical pharmacist provided interpretation and recommendations from genotyping results...
April 2017: Pharmacy Practice
https://www.readbyqxmd.com/read/28689434/role-of-genetic-testing-in-patients-undergoing-percutaneous-coronary-intervention
#12
Jae Youn Moon, Francesco Franchi, Fabiana Rollini, Jose R Rivas Rios, Megha Kureti, Larisa H Cavallari, Dominick J Angiolillo
Variability in individual response profiles to antiplatelet therapy, in particular clopidogrel, is a well-established phenomenon. Genetic variations of the cytochrome P450 (CYP) 2C19 enzyme, a key determinant in clopidogrel metabolism, have been associated with clopidogrel response profiles. Moreover, the presence of a CYP2C19 loss-of-function allele is associated with an increased risk of atherothrombotic events among clopidogrel-treated patients undergoing percutaneous coronary interventions (PCI), prompting studies evaluating the use of genetic tests to identify patients who may be potential candidates for alternative platelet P2Y12 receptor inhibiting therapies (prasugrel or ticagrelor)...
July 10, 2017: Expert Review of Clinical Pharmacology
https://www.readbyqxmd.com/read/28685204/time-course-of-the-antiplatelet-effect-after-switching-to-clopidogrel-from-initial-prasugrel-therapy-in-patients-with-acute-coronary-syndrome
#13
Erito Furuse, Hitoshi Takano, Takeshi Yamamoto, Yoshiaki Kubota, Takashi Yoshizane, Mitsunobu Kitamura, Hideki Miyachi, Yusuke Hosokawa, Wataru Shimizu
Prasugrel is often replaced with clopidogrel after a certain period of time following coronary stenting. However, the time course of platelet aggregation during this replacement is unknown. We performed a prospective, single-arm study to monitor platelet reactivity before and after the replacement. Forty-five patients (mean age 62.6 ± 13 years, 40 male) who received coronary stenting for acute coronary syndrome were initially treated with the loading dose (20 mg) of prasugrel followed by the maintenance dose (3...
July 6, 2017: Heart and Vessels
https://www.readbyqxmd.com/read/28684062/intracoronary-high-dose-bolus-tirofiban-administration-during-complex-coronary-interventions-a-united-states-based-case-series
#14
Charles I Wilmer
The GP IIb/IIIa inhibitors (GPIs) rapidly provide therapeutic levels of platelet aggregation inhibition and serve as adjunct pharmacotherapy to oral P2Y12 inhibitors that exhibit a significant delay in onset of action for patients with Acute Coronary Syndrome (ACS). Intracoronary (IC) administration of the high dose bolus (HDB) tirofiban has not been extensively studied. Compared to intravenous delivery, IC administration can lead to higher local drug concentration and, therefore, provide instantaneous disruption of platelet aggregation in the culprit vessel...
June 22, 2017: Cardiovascular Revascularization Medicine: Including Molecular Interventions
https://www.readbyqxmd.com/read/28681220/comparison-of-platelet-aggregation-response-in-switching-regimen-from-prasugrel-to-clopidogrel-between-cyp2c19-extensive-versus-non-extensive-metabolizers
#15
Soichiro Ebisawa, Yasushi Ueki, Tomoaki Mochidome, Keisuke Senda, Hitoshi Nishimura, Tatsuya Saigusa, Takashi Miura, Hirohiko Motoki, Jun Koyama, Uichi Ikeda
Little is known about the response of platelet aggregation in patients with acute coronary syndrome (ACS) when prasugrel is changed to clopidogrel. In this study, we evaluated the pharmacodynamic effects of this medication switch. Twenty-one consecutive ACS patients received prasugrel 20 mg as a loading dose before emergent percutaneous coronary intervention and 3.75 mg as a maintenance dose on days 2-7 (prasugrel phase). From day 8, prasugrel was switched to clopidogrel 75 mg/day (clopidogrel phase). P2Y12 reaction units (PRU) were measured 2-4 h after prasugrel loading, and on days 7, 11, 13, 15, and 42...
July 5, 2017: Cardiovascular Intervention and Therapeutics
https://www.readbyqxmd.com/read/28679740/role-of-adp-receptors-on-platelets-in-the-growth-of-ovarian-cancer
#16
Min Soon Cho, Kyunghee Noh, Monika Haemmerle, Dan Li, Hyun Park, Qianghua Hu, Takeshi Hisamatsu, Takashi Mitamura, Sze Ling Celia Mak, Satya Kunapuli, Qing Ma, Anil K Sood, Vahid Afshar-Kharghan
We investigated the effect of platelets on ovarian cancer, and role of ADP receptors (P2Y12 and P2Y1) on platelets in the growth of primary ovarian cancer tumors. We showed that in murine models of ovarian cancer, P2Y12 inhibitor (Ticagrelor) reduced tumor growth by 60% compared to aspirin and 75% compared to placebo. In P2Y12(-/-) mice, the growth of syngeneic ovarian cancer tumors was reduced by >85% compared to WT mice. On the other hand, there was no difference in the tumor growth between P2Y1(-/-) and WT mice...
July 5, 2017: Blood
https://www.readbyqxmd.com/read/28675986/clinical-determinants-of-clopidogrel-responsiveness-in-a-heterogeneous-cohort-of-puerto-rican-hispanics
#17
Dagmar F Hernandez-Suarez, Stuart A Scott, Matthew I Tomey, Kyle Melin, Angel Lopez-Candales, Charlotte E Buckley, Jorge Duconge
BACKGROUND: Clopidogrel is by far the most prescribed platelet adenosine diphosphate (ADP) antagonist in Puerto Rico despite the advent of newer agents (prasugrel and ticagrelor). Given the paucity of data on clopidogrel responsiveness in Hispanics, we sought to determine the association between clinical characteristics and platelet reactivity in Puerto Rican patients on clopidogrel therapy. STUDY POPULATION: A total of 100 Puerto Rican patients on clopidogrel therapy were enrolled and allocated into two groups: Group I, without high on-treatment platelet reactivity (HTPR); and Group II, with HTPR...
July 1, 2017: Therapeutic Advances in Cardiovascular Disease
https://www.readbyqxmd.com/read/28674626/implications-of-the-pegasus-timi-54-trial-for-us-clinical-practice
#18
Steven M Bradley, Gregory P Hess, Patrick Stewart, Ehrin J Armstrong, Steven A Farmer, Jason H Wasfy, Javier Alfonso Valle, Amneet Sandhu, Thomas M Maddox
OBJECTIVES: This study aims to determine the proportion of real-world patients with myocardial infarction (MI) who would have been eligible for the PEGASUS-TIMI 54 (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, to characterise their current use of P2Y12 inhibitors and to explore the estimated costs and ischaemic event consequences of increasing P2Y12 inhibitor use among these patients...
2017: Open Heart
https://www.readbyqxmd.com/read/28667163/leukotriene-c4-potentiates-il-33-induced-group-2-innate-lymphoid-cell-activation-and-lung-inflammation
#19
Sean J Lund, Alex Portillo, Kellen Cavagnero, Rachel E Baum, Luay H Naji, Jana H Badrani, Amit Mehta, Michael Croft, David H Broide, Taylor A Doherty
Asthma is a complex disease that is promoted by dysregulated immunity and the presence of many cytokine and lipid mediators. Despite this, there is a paucity of data demonstrating the combined effects of multiple mediators in asthma pathogenesis. Group 2 innate lymphoid cells (ILC2s) have recently been shown to play important roles in the initiation of allergic inflammation; however, it is unclear whether lipid mediators, such as cysteinyl leukotrienes (CysLTs), which are present in asthma, could further amplify the effects of IL-33 on ILC2 activation and lung inflammation...
June 30, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28663045/appropriateness-assessment-in-antiplatelet-therapy-apathy-registry-insight-from-current-clinical-practice
#20
Nazario Carrabba, Benedetta Bellandi, Guido Parodi, Emanuele Cecchi, Giorgio Baldereschi, Cristina Giglioli, Angela Migliorini, Renato Valenti, Serafina Valente, Rossella Marcucci, Niccolò Marchionni, David Antoniucci
BACKGROUND: In clinical practice there is a gap between guidelines recommendation and antiplatelet strategies used for acute coronary syndrome (ACS). We sought to evaluate appropriateness of antiplatelet strategies employed in a tertiary center. METHODS AND RESULTS: From January to June 2014, 430 ACS were treated with percutaneous coronary intervention by 3 groups of interventional cardiologists. Aspirin and clopidogrel (52%) were the most commonly used antiplatelet therapies, being prasugrel associated with aspirin in 110 (25...
June 21, 2017: International Journal of Cardiology
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