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https://www.readbyqxmd.com/read/27920074/a-critical-appraisal-of-aspirin-in-secondary-prevention-is-less-more
#1
Giuseppe Gargiulo, Stephan Windecker, Pascal Vranckx, Charles Michael Gibson, Roxana Mehran, Marco Valgimigli
Aspirin represents the sine qua non for antiplatelet pharmacotherapy in patients with cardiovascular diseases because of its well-established role in secondary prevention and its widespread availability and affordability. Historical studies, conducted in an era that bears little resemblance to contemporary clinical practice, demonstrated large reductions in thrombotic risk when aspirin was compared with placebo, thus forming the evidence base promulgated in practice guidelines and recommendations. P2Y12 inhibitors have mostly been studied in addition to aspirin; dual-antiplatelet therapy proved superiority compared with aspirin monotherapy for the prevention of ischemic events, despite increased bleeding risks...
December 6, 2016: Circulation
https://www.readbyqxmd.com/read/27914492/ticagrelor-with-aspirin-or-alone-in-high-risk-patients-after-coronary-intervention-rationale-and-design-of-the-twilight-study
#2
Usman Baber, George Dangas, David J Cohen, C Michael Gibson, Shamir R Mehta, Dominick J Angiolillo, Stuart J Pocock, Mitchell W Krucoff, Adnan Kastrati, E Magnus Ohman, Philippe Gabriel Steg, Juan Badimon, M Urooj Zafar, Jaya Chandrasekhar, Samantha Sartori, Melissa Aquino, Roxana Mehran
BACKGROUND: Dual antiplatelet therapy (DAPT) is necessary to prevent thrombosis yet increases bleeding after percutaneous coronary intervention (PCI) with drug-eluting stents (DES). Antiplatelet monotherapy with a potent P2Y12 receptor antagonist may reduce bleeding while maintaining anti thrombotic efficacy compared with conventional DAPT. METHODS: TWILIGHT is a randomized, double-blind placebo-controlled trial evaluating the comparative efficacy and safety of antiplatelet monotherapy versus DAPT in up to 9000 high-risk patients undergoing PCI with DES...
December 2016: American Heart Journal
https://www.readbyqxmd.com/read/27904901/effect-of-ticagrelor-on-endothelial-calcium-signalling-and-barrier-function
#3
Dursun Gündüz, Christian Tanislav, Klaus-Dieter Schlüter, Rainer Schulz, Christian Hamm, Muhammad Aslam
The P2Y12 receptor is a Gi-coupled receptor whose activation inhibits adenylyl cyclase and thereby reduces the concentration of intracellular cAMP. Here the hypothesis was tested whether AR-C 66096 or ticagrelor, two direct-acting and reversibly binding P2Y12 receptor antagonists, protect endothelial cell (EC) barrier function by raising intracellular cAMP in ECs. The study was carried out on primary human umbilical vein ECs (HUVECs) and human pulmonary microvascular ECs (hPMECs). AR-C66096 (10 µM) induced a 50 % increase in cAMP in ECs whereas ticagrelor (2-10 µM) had no effect...
December 1, 2016: Thrombosis and Haemostasis
https://www.readbyqxmd.com/read/27902833/evaluation-of-ischemic-and-bleeding-risks-associated-with-2-parenteral-antiplatelet-strategies-comparing-cangrelor-with-glycoprotein-iib-iiia-inhibitors-an-exploratory-analysis-from-the-champion-trials
#4
Muthiah Vaduganathan, Robert A Harrington, Gregg W Stone, Efthymios N Deliargyris, Ph Gabriel Steg, C Michael Gibson, Christian W Hamm, Matthew J Price, Alberto Menozzi, Jayne Prats, Steven Elkin, Kenneth W Mahaffey, Harvey D White, Deepak L Bhatt
Importance: In the context of contemporary pharmacotherapy, optimal antiplatelet management with percutaneous coronary intervention (PCI) has not been well established. Objective: To compare the ischemic and bleeding risks associated with glycoprotein IIb/IIIa inhibitors (GPIs) and a potent P2Y12 antagonist, cangrelor, in patients undergoing PCI. Design, Setting, and Participants: An exploratory analysis of pooled patient-level data from the 3 phase 3 Cangrelor vs Standard Therapy to Achieve Optimal Management of Platelet Inhibition (CHAMPION PCI, CHAMPION PLATFORM, and CHAMPION PHOENIX) trials of patients undergoing elective or nonelective PCI...
November 30, 2016: JAMA Cardiology
https://www.readbyqxmd.com/read/27886824/switching-p2y12-receptor-inhibiting-therapies
#5
REVIEW
Fabiana Rollini, Francesco Franchi, Dominick J Angiolillo
Antiplatelet therapy with aspirin and a P2Y12 receptor inhibitor is the cornerstone of treatment of patients with atherothrombotic disease manifestations. Switching between P2Y12 inhibitors occurs commonly in clinical practice for a variety of reasons, including safety, efficacy, adherence, and economic considerations. There are concerns about the optimal approach for switching because of potential drug interactions, which may lead to ineffective platelet inhibition and thrombotic complications, or potential overdosing due to overlap in drug therapy, which might cause excessive platelet inhibition and increased bleeding...
January 2017: Interventional cardiology clinics
https://www.readbyqxmd.com/read/27886822/ticagrelor-effects-beyond-the-p2y12-receptor
#6
REVIEW
Wael Sumaya, Robert F Storey
Platelet P2Y12 receptor inhibitors are crucial in the treatment of patients with acute coronary syndrome or undergoing percutaneous coronary intervention. Ticagrelor is a reversibly binding, potent oral P2Y12 inhibitor that also is a weak inhibitor of the equilibrative nucleoside transporter-1 pathway for cellular adenosine uptake. It is hypothesized that ticagrelor has clinically relevant "off-target" effects, independent of its effect on platelet aggregation and thrombosis. This review considers the pleiotropic effects of ticagrelor and some of the possible mechanisms related to these effects...
January 2017: Interventional cardiology clinics
https://www.readbyqxmd.com/read/27886821/cangrelor-pharmacology-clinical-data-and-role-in-percutaneous-coronary-intervention
#7
REVIEW
Matthew J Price
In clinical trials that assessed the safety and efficacy of cangrelor during percutaneous coronary intervention (PCI), cangrelor was administered as a 30-μg/kg bolus followed by a 4-μg/kg/min infusion for at least 2 hours or the duration of the PCI, whichever was longer. Cangrelor is currently indicated as an adjunct to PCI to reduce the risk of myocardial infarction, repeat coronary revascularization, and stent thrombosis in patients who have not been treated with a P2Y12 platelet inhibitor and are not being given a glycoprotein IIb/IIIa inhibitor...
January 2017: Interventional cardiology clinics
https://www.readbyqxmd.com/read/27886818/genetic-determinants-of-p2y12-inhibitors-and-clinical-implications
#8
REVIEW
Larisa H Cavallari, Aniwaa Owusu Obeng
There is significant interpatient variability in clopidogrel effectiveness, which is due in part to cytochrome P450 (CYP) 2C19 genotype. Approximately 30% of individuals carry CYP2C19 loss-of-function alleles, which have been consistently shown to reduce clopidogrel effectiveness after an acute coronary syndrome and percutaneous coronary intervention. Guidelines recommend consideration of prasugrel or ticagrelor in these patients. A clinical trial examining outcomes with CYP2C19 genotype-guided antiplatelet therapy is ongoing...
January 2017: Interventional cardiology clinics
https://www.readbyqxmd.com/read/27886817/antithrombotic-therapy-to-reduce-ischemic-events-in-acute-coronary-syndromes-patients-undergoing-percutaneous-coronary-intervention
#9
REVIEW
Freek W A Verheugt
Antithrombotic therapy is essential in the prevention of periprocedural death and myocardial infarction during and after percutaneous coronary intervention. In the pathogenesis of acute coronary syndromes (ACS), both platelets and the coagulation cascade play an important role. Therefore, periprocedural antithrombotic therapy is even more important in ACS than in elective PCI. The most used agents are aspirin, platelet P2Y12 blockers, platelet glycoprotein IIb/IIIa blockers, and parenteral anticoagulants. The P2Y12 blockers must be continued at least 12 months...
January 2017: Interventional cardiology clinics
https://www.readbyqxmd.com/read/27886816/pretreatment-with-antiplatelet-agents-in-the-setting-of-percutaneous-coronary-intervention-when-and-which-drugs
#10
REVIEW
Davide Capodanno, Dominick J Angiolillo
Administering antiplatelet agents before coronary angiography to patients referred to elective or urgent percutaneous coronary intervention (PCI) requires a careful evaluation of advantages and disadvantages associated with platelet inhibition to avoid overtreatment on one side and undertreatment on the other. The delicate balance between ischemic protection and bleeding demands the ability to undertake risk stratification and individualized decisions, which is particularly challenging in the setting of ad hoc PCI and urgent procedures...
January 2017: Interventional cardiology clinics
https://www.readbyqxmd.com/read/27885904/the-effect-of-p2y12-inhibition-on-platelet-activation-assessed-with-aggregation-and-flow-cytometry-based-assays
#11
Tesse C Leunissen, Peter Paul Wisman, Thijs C van Holten, Philip G de Groot, Suzanne J Korporaal, Arnold C Koekman, Frans L Moll, Martin Teraa, Marianne C Verhaar, Gert Jan de Borst, Rolf T Urbanus, Mark Roest
Patients on P2Y12 inhibitors may still develop thrombosis or bleeding complications. Tailored antiplatelet therapy, based on platelet reactivity testing, might reduce these complications. Several tests have been used, but failed to show a benefit of tailored antiplatelet therapy. This could be due to the narrowness of current platelet reactivity tests, which are limited to analysis of platelet aggregation after stimulation of the adenosine diphosphate (ADP)-pathway. However, the response to ADP does not necessarily reflect the effect of P2Y12 inhibition on platelet function in vivo...
November 25, 2016: Platelets
https://www.readbyqxmd.com/read/27885888/cangrelor-in-combination-with-ticagrelor-provides-consistent-and-potent-p2y12-inhibition-during-and-after-primary-percutaneous-coronary-intervention-in-real-world-patients-with-st-segment-elevation-myocardial-infarction
#12
Moman A Mohammad, Pontus Andell, Sasha Koul, Stefan James, Fredrik Scherstén, Matthias Götberg, David Erlinge
Patients pretreated with ticagrelor with less than 1 hour from percutaneous coronary intervention (PCI) or receiving ticagrelor in cath lab were prospectively included and received cangrelor. Cangrelor was infused for 2 hours and platelet function was assessed as P2Y12 reactivity units (PRU) with the VerifyNow P2Y12 function assay before start of infusion, 15 min after the start of infusion, and 30 min after the end of infusion. A total of n = 32 patients with an average age of 68 (±13) years with n = 22 (69%) males were included...
November 25, 2016: Platelets
https://www.readbyqxmd.com/read/27881555/recurrent-hospitalization-among-patients-with-atrial-fibrillation-undergoing-intracoronary-stenting-treated-with-2-treatment-strategies-of-rivaroxaban-or-a-dose-adjusted-oral-vitamin-k-antagonist-treatment-strategy
#13
C Michael Gibson, Duane S Pinto, Gerald Chi, Douglas Arbetter, Megan Yee, Roxana Mehran, Christoph Bode, Jonathan Halperin, Freek W A Verheugt, Peter Wildgoose, Paul Burton, Martin van Eickels, Serge Korjian, Yazan Daaboul, Purva Jain, Gregory Y H Lip, Marc Cohen, Eric D Peterson, Keith A A Fox
BACKGROUND: -Patients with atrial fibrillation who undergo intracoronary stenting traditionally are treated with a vitamin K antagonist (VKA) plus dual antiplatelet therapy (DAPT), yet this treatment leads to high risks of bleeding. We hypothesized that a regimen of rivaroxaban plus a P2Y12 inhibitor monotherapy or rivaroxaban plus DAPT could reduce bleeding and thereby have a favorable impact on all-cause mortality and the need for rehospitalization. METHODS: -Stented subjects with nonvalvular atrial fibrillation (n=2124) were randomized 1:1:1 to administration of reduced-dose rivaroxaban 15 mg daily plus a P2Y12 inhibitor for 12 months (group 1); rivaroxaban 2...
November 14, 2016: Circulation
https://www.readbyqxmd.com/read/27871553/fascia-iliaca-block-associated-only-with-deep-sedation-in-high-risk-patients-taking-p2y12-receptor-inhibitors-for-intramedullary-femoral-fixation-in-intertrochanteric-hip-fracture-a-series-of-3-cases
#14
Carlos Rodrigues Almeida, Emília Milheiro Francisco, Vítor Pinho-Oliveira, José Pedro Assunção
OBJECTIVE: We present a series of 3 cases in which the impact in outcome was, first of all, related to the capacity to offer early and safer treatment to some hip fracture high-risk patients using a fascia iliaca block (FIB; ropivacaine 0,5% 20 cc and mepivacaine 1,3% 15 cc, given 30 minutes before incision) associated only with deep sedation, contributing to better practice and outcome. CASE REPORTS: All elderly patients were American Society of Anesthesiologists IV patients, under P2Y12 receptor inhibitors, suffering from an intertrochanteric fracture, and purposed for intramedullary femoral fixation (IMF)...
December 2016: Journal of Clinical Anesthesia
https://www.readbyqxmd.com/read/27867285/lower-platelet-reactivity-is-associated-with-presentation-of-unstable-coronary-artery-disease
#15
Tesse C Leunissen, Crystel M Gijsberts, Peter Paul Wisman, Albert Huisman, Maarten Ten Berg, Folkert W Asselbergs, Imo E Hoefer, Gerard Pasterkamp, Frans L Moll, Gert Jan de Borst, Mark Roest
In patients with acute coronary syndrome, high platelet reactivity (PR) is associated with an increased risk of secondary thrombotic events. However, in patients undergoing elective percutaneous coronary intervention (PCI), no association between high PR and outcome has been demonstrated. At present, the relation of PR and clinical symptoms is unknown. To examine the association of PR with clinical indication for diagnostic angiography (stable or unstable coronary artery disease [CAD]), taking into account the influence of P2Y12 inhibitors...
December 2016: International Journal of Angiology: Official Publication of the International College of Angiology, Inc
https://www.readbyqxmd.com/read/27867196/extracellular-adp-facilitates-monocyte-recruitment-in-bacterial-infection-via-erk-signaling
#16
Xiaoyu Zhang, Juliang Qin, Junyan Zou, Zhangsheng Lv, Binghe Tan, Jueping Shi, Yihan Zhao, Hua Ren, Mingyao Liu, Min Qian, Bing Du
As the most prominent clinical drug targets for the inhibition of platelet aggregation, P2Y12 and P2Y13 have been found to be highly expressed in both platelets and macrophages. However, the roles and function of P2Y12/13 in the regulation of macrophage-mediated innate immune responses remain unclear. Here, we demonstrate that adenosine 5'-diphosphate (ADP), the endogenous ligand of P2Y1, P2Y12 and P2Y13, was released both in E. coli-infected mice and from macrophages treated with either lipopolysaccharide (LPS) or Pam3CSK4...
November 21, 2016: Cellular & Molecular Immunology
https://www.readbyqxmd.com/read/27865197/efficacy-and-safety-of-ticagrelor-versus-clopidogrel-with-different-dosage-in-high-risk-patients-with-acute-coronary-syndrome
#17
Yan-Guo Xin, Hai-Shan Zhang, Yu-Ze Li, Qi-Gang Guan, Liang Guo, Yuan Gao, Hai-Jie Yu, Xin-Gang Zhang, Feng Xu, Yue-Lan Zhang, Da-Lin Jia, Ying-Xian Sun, Guo-Xian Qi, Wen Tian
BACKGROUND: Dual antiplatelet therapy is recommended as a standard antiplatelet strategy in acute coronary syndrome. For those with reduced pharmacologic response to clopidogrel, strengthening antiplatelet therapy (clopidogrel 150mg daily) may reduce adverse clinical events. Ticagrelor is a direct-acting inhibitor of the adenosine diphosphate receptor P2Y12 that has a more rapid onset and offset than clopidogrel. METHODS: In this retrospective study, we compared ticagrelor (180mg loading dose 90mg twice daily thereafter), clopidogrel (300mg loading dose, 75mg or 150mg daily thereafter) for the prevention of cardiovascular events in 273 high-risk patients admitted to coronary care unit with acute coronary syndrome...
November 9, 2016: International Journal of Cardiology
https://www.readbyqxmd.com/read/27864383/use-of-pharmacogenetic-information-in-the-treatment-of-cardiovascular-disease
#18
REVIEW
Kevin Friede, Josephine Li, Deepak Voora
BACKGROUND: In 1964, Robert A. O'Reilly's research group identified members of a family who required remarkably high warfarin doses (up to 145 mg/day, 20 times the average dose) to achieve appropriate anticoagulation. Since this time, pharmacogenetics has become a mainstay of cardiovascular science, and genetic variants have been implicated in several fundamental classes of medications used in cardiovascular medicine. CONTENT: In this review, we discuss genetic variants that affect drug response to 3 classes of cardiovascular drugs: statins, platelet P2Y12 inhibitors, and anticoagulants...
November 18, 2016: Clinical Chemistry
https://www.readbyqxmd.com/read/27862351/p2y12-receptor-is-expressed-on-human-microglia-under-physiological-conditions-throughout-development-and-is-sensitive-to-neuroinflammatory-diseases
#19
Alexander Mildner, Hao Huang, Josefine Radke, Werner Stenzel, Josef Priller
Microglia are resident immune cells in the central nervous system (CNS), which are essential for immune defence and critically contribute to neuronal functions during homeostasis. Until now, little is known about microglia biology in humans in part due to the lack of microglia-specific markers. We therefore investigated the expression of the purinergic receptor P2Y12 in human brain tissue. Compared to classical markers used to identify microglia such as Iba1, CD68 or MHCII, we found that P2Y12 is expressed on parenchymal microglia but is absent from perivascular or meningeal macrophages...
November 12, 2016: Glia
https://www.readbyqxmd.com/read/27854064/the-rationale-for-and-clinical-pharmacology-of-prasugrel-5-mg
#20
REVIEW
Joseph A Jakubowski, David Erlinge, Dimitrios Alexopoulos, David S Small, Kenneth J Winters, Paul A Gurbel, Dominick J Angiolillo
Prasugrel is a third-generation thienopyridine platelet P2Y12 adenosine diphosphate (ADP) receptor antagonist administered with aspirin for the treatment of patients with acute coronary syndrome (ACS) with planned percutaneous coronary intervention. Prasugrel is administered periprocedurally at an oral loading dose of 60 mg followed by daily maintenance doses (MDs) of 10 mg for most patients and 5 mg for patients weighing <60 kg or aged ≥75 years. Data from a prasugrel phase III study, TRITON-TIMI 38, suggested that a lower MD might be more suitable for patients weighing <60 kg or aged ≥75 years; subsequent pharmacokinetic and pharmacodynamic studies have indicated that prasugrel 5 mg reduced platelet reactivity in these populations to an extent similar to that of prasugrel 10 mg in heavier or younger patients...
November 17, 2016: American Journal of Cardiovascular Drugs: Drugs, Devices, and Other Interventions
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