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P2Y12

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https://www.readbyqxmd.com/read/28420804/contemporary-trends-and-outcomes-associated-with-the-preprocedural-use-of-oral-p2y12-inhibitors-in-patients-undergoing-percutaneous-coronary-intervention-insights-from-the-blue-cross-blue-shield-of-michigan-cardiovascular-consortium-bmc2
#1
Devraj Sukul, Milan Seth, Simon R Dixon, Akshay Khandelwal, Thomas A LaLonde, Hitinder S Gurm
OBJECTIVES: We sought to describe trends in the use of preprocedural P2Y12 inhibitors and their clinical impact in patients undergoing percutaneous coronary intervention (PCI). BACKGROUND: Oral P2Y12 inhibitors are ubiquitously used medications; however, the specific timing of initial P2Y12 inhibitor administration remains intensely debated. METHODS: Our study population comprised 74,053 consecutive patients undergoing PCI at 47 hospitals in Michigan from January 2013 through June 2015...
April 15, 2017: Journal of Invasive Cardiology
https://www.readbyqxmd.com/read/28408884/effect-of-cyp3a4-%C3%A2-1g-and-cyp3a5-%C3%A2-3-polymorphisms-on-pharmacokinetics-and-pharmacodynamics-of-ticagrelor-in-healthy-chinese-subjects
#2
Shuaibing Liu, Xiangfen Shi, Xin Tian, Xiaojian Zhang, Zhiyong Sun, Liyan Miao
Ticagrelor is the first reversible, direct-acting, potent P2Y12 receptor antagonist in management of acute coronary syndromes. It is rapidly absorbed and extensively metabolized. AR-C124910XX, the major active metabolite, antagonizes the P2Y12 receptor at approximately equal potency. The metabolism of ticagrelor to AR-C124910XX involves CYP3A4 and CYP3A5. CYP3A polymorphisms have been well documented, and CYP3A4(∗)1G (g.20230G>A, rs2242480) and CYP3A5(∗)3 (g.6986A>G, rs776746) are the most important single nucleotide polymorphisms in Chinese...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28403576/no-pharmacokinetic-drug-drug-interaction-between-prasugrel-and-vorapaxar-following-multiple-dose-administration-in-healthy-volunteers
#3
Matt S Anderson, Teddy Kosoglou, Paul Statkevich, Jing Li, Jennifer Rotonda, Alan G Meehan, David L Cutler
Vorapaxar is a first-in-class antagonist of the protease-activated receptor-1, the primary thrombin receptor on human platelets, which mediates the downstream effects of thrombin in hemostasis and thrombosis. Prasugrel is a platelet inhibitor that acts as a P2Y12 receptor antagonist through an active metabolite, R-138727. This study investigated the interaction of these 2 platelet antagonists when coadministered. This was a randomized, open-label, multiple-dose study in 54 healthy volunteers consisting of a fixed-sequence crossover and a parallel group design...
April 12, 2017: Clinical Pharmacology in Drug Development
https://www.readbyqxmd.com/read/28400185/purification-and-characterization-of-cc-lec-c-type-lactose-binding-lectin-a-platelet-aggregation-and-blood-clotting-inhibitor-from-cerastes-cerastes-venom
#4
Saoud Samah, Chérifi Fatah, Berjeaud Jean-Marc, Kellou-Taîri Safia, Laraba-Djebari Fatima
In this study, we reported for the first time the biochemical and structural characterization of Cc-Lec, a C-type lectin purified from Cerastes cerastes venom by affinity chromatography. This lectin was homogeneous by SDS-PAGE, and was shown to be a 34 271.59Da polypeptide by Electrospray mass spectrometry MS-ES-TOF. Its identified sequence of 160 amino acids corresponding to one subunit, revealed a high identity with other related proteins. Cc-Lec modeled 3D structure appeared as homodimer cross-linked by one disulfide bridge...
April 8, 2017: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/28399648/the-highly-selective-caspase-1-inhibitor-vx-765-provides-additive-protection-against-myocardial-infarction-in-rat-hearts-when-combined-with-a-platelet-inhibitor
#5
Xi-Ming Yang, James M Downey, Michael V Cohen, Nicole A Housley, Diego F Alvarez, Jonathon P Audia
Use of ischemic postconditioning and other related cardioprotective interventions to treat patients with acute myocardial infarction (AMI) has failed to improve outcomes in clinical trials. Because P2Y12 inhibitors are themselves postconditioning mimetics, it has been postulated that the loading dose of platelet inhibitors routinely given to patients treated for AMI masks the anti-infarct effect of other intended cardioprotective interventions. To further improve outcomes of patients with AMI, an intervention must be able to provide additive protection in the presence of a P2Y12 platelet inhibitor...
January 1, 2017: Journal of Cardiovascular Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/28392699/comparison-of-prophylactic-effect-of-ugib-and-effects-on-platelet-function-between-ppis-and-h2ras-combined-with-dapt-systematic-review-and-meta-analysis
#6
Zhan-Miao Yi, Ting-Ting Qiu, Yuan Zhang, Zhi-Yan Liu, Suo-Di Zhai
OBJECTIVE: We compared prophylactic effects of proton pump inhibitors (PPIs) and histamine-2 receptor antagonists (H2RAs) on upper gastrointestinal bleeding (UGIB) associated with dual antiplatelet therapy (DAPT) and explored this influence on platelet function. METHODS: Randomized controlled trials and cohort studies comparing PPIs with H2RAs in adults receiving DAPT were collected from PubMed, EMBASE and Cochrane databases. Dichotomous data were pooled to obtain risk ratios (RRs) for UGIB, major adverse cardiovascular events (MACEs), poor responders to clopidogrel and rehospitalization, and continuous data were pooled to obtain mean differences (MDs) for P2Y12 reaction units (PRUs), with 95% confidence intervals (CIs)...
2017: Therapeutics and Clinical Risk Management
https://www.readbyqxmd.com/read/28391744/malignant-stroke-in-a-ticagrelor-non-responder-as-a-complication-following-aneurysm-treatment-with-the-pipeline-embolization-device%C3%A2
#7
Pegah Ghamasaee, Kevin Carr, Jeremiah Johnson, Ramesh Grandhi
The Pipeline Embolization Device™ (PED; Covidien Neurovascular Inc, Irvine, CA, USA) is a flow-diverting stent often used for the endovascular treatment of large or giant, wide-necked intracranial aneurysms of the internal carotid artery. Because of the inherent thrombogenicity of intracranial stents, dual-antiplatelet therapy is initiated after placement, which has been shown to decrease morbidity and mortality related to perioperative ischemic events in neurointerventional procedures. However, in some series, as much as 50% of patients demonstrate clopidogrel non-responsiveness...
January 1, 2017: Interventional Neuroradiology
https://www.readbyqxmd.com/read/28385176/meta-analysis-of-the-relative-efficacy-and-safety-of-oral%C3%A2-p2y12-inhibitors-in-patients-with-acute-coronary%C3%A2-syndrome
#8
Rahman Shah, Abdul Rashid, Inyong Hwang, Tai-Hwang M Fan, Rami N Khouzam, Guy L Reed
A cornerstone of medical therapy for patients with acute coronary syndrome (ACS) is dual antiplatelet therapy, which includes aspirin and a P2Y12 inhibitor. Randomized controlled trials (RCTs) have shown that prasugrel and ticagrelor are superior to clopidogrel, but none directly compared these 3 commonly used oral P2Y12 inhibitors for safety and efficacy. Therefore, we performed a Bayesian network meta-analysis of RCTs to compare the efficacies and safeties of 3 commonly used oral P2Y12 inhibitors in patients with ACS...
March 16, 2017: American Journal of Cardiology
https://www.readbyqxmd.com/read/28382371/characteristics-of-dyspnoea-and-associated-clinical-outcomes-in-the-champion-phoenix-study
#9
William A Parker, Deepak L Bhatt, Jayne Prats, Jonathan R S Day, Philippe Gabriel Steg, Gregg W Stone, Christian W Hamm, Kenneth W Mahaffey, Matthew J Price, C Michael Gibson, Harvey D White, Robert F Storey
Dyspnoea may be induced by some reversibly-binding P2Y12 inhibitors, including cangrelor and ticagrelor. Dyspnoea was not associated with any compromise to the efficacy of ticagrelor in the PLATO study. The CHAMPION PHOENIX study (NCT01156571) compared initial treatment with cangrelor versus initial treatment with clopidogrel in patients undergoing PCI. We investigated the incidence, characteristics, and associated clinical outcomes in patients with dyspnoea in CHAMPION PHOENIX. Adverse events (AEs) of dyspnoea to 48 hours were recorded in patients randomised to cangrelor or clopidogrel in CHAMPION PHOENIX...
April 6, 2017: Thrombosis and Haemostasis
https://www.readbyqxmd.com/read/28381584/predicting-the-risk-of-bleeding-during-dual-antiplatelet-therapy-after-acute-coronary-syndromes
#10
Joakim Alfredsson, Benjamin Neely, Megan L Neely, Deepak L Bhatt, Shaun G Goodman, Pierluigi Tricoci, Kenneth W Mahaffey, Jan H Cornel, Harvey D White, Keith Aa Fox, Dorairaj Prabhakaran, Kenneth J Winters, Paul W Armstrong, E Magnus Ohman, Matthew T Roe
OBJECTIVES: Dual antiplatelet therapy (DAPT) with aspirin + a P2Y12 inhibitor is recommended for at least 12 months for patients with acute coronary syndrome (ACS), with shorter durations considered for patients with increased bleeding risk. However, there are no decision support tools available to predict an individual patient's bleeding risk during DAPT treatment in the post-ACS setting. METHODS: To develop a longitudinal bleeding risk prediction model, we analysed 9240 patients with unstable angina/non-ST segment elevation myocardial infarction (NSTEMI) from the Targeted Platelet Inhibition to Clarify the Optimal Strategy to Medically Manage Acute Coronary Syndromes (TRILOGY ACS) trial, who were managed without revascularisation and treated with DAPT for a median of 14...
April 5, 2017: Heart: Official Journal of the British Cardiac Society
https://www.readbyqxmd.com/read/28381298/ticagrelor-versus-clopidogrel-in-real-world-patients-with-st-elevation-myocardial-infarction-1-year-results-by-propensity-score-analysis
#11
Matteo Vercellino, Federico Ariel Sànchez, Valentina Boasi, Dino Perri, Chiara Tacchi, Gioel Gabrio Secco, Stefano Cattunar, Gianfranco Pistis, Giovanni Mascelli
BACKGROUND: European guidelines recommend the use of ticagrelor versus clopidogrel in patients with ST elevation myocardial infarction (STEMI). This recommendation is based on inconclusive results and subanalyses from clinical trials. Few data are available on the effects of ticagrelor in a real-world population. METHODS: To compare the effects of ticagrelor and clopidogrel in a real-world STEMI population, we conducted a pre-post case-control study examining all patients with STEMI included in the Cardio-STEMI Sanremo registry between February 2011 and June 2013...
April 5, 2017: BMC Cardiovascular Disorders
https://www.readbyqxmd.com/read/28381198/effect-of-ticagrelor-with-clopidogrel-on-high-on-treatment-platelet-reactivity-in-acute-stroke-or-transient-ischemic-attack-prince-trial-rationale-and-design
#12
Yilong Wang, Yi Lin, Xia Meng, Weiqi Chen, Guohua Chen, Zhimin Wang, Jialing Wu, Dali Wang, Jianhua Li, Yibin Cao, Yuming Xu, Guohua Zhang, Xiaobo Li, Yuesong Pan, Hao Li, Liping Liu, Xingquan Zhao, Yongjun Wang
Rationale and aim Little is known about the safety and efficacy of the combination of ticagrelor and aspirin in acute ischemic stroke. This study aimed to evaluate whether the combination of ticagrelor and aspirin was superior to that of clopidogrel and aspirin in reducing the 90-day high on-treatment platelet reactivity for acute minor stroke or transient ischemic attack, especially for carriers of cytochrome P450 2C19 loss-of-function allele. Sample size and design This study was designed as a prospective, multicenter, randomized, open-label, active-controlled, and blind-endpoint, phase II b trial...
April 2017: International Journal of Stroke: Official Journal of the International Stroke Society
https://www.readbyqxmd.com/read/28379902/cangrelor-a-new-route-for-p2y12-inhibition
#13
Alexandra M Sible, James J Nawarskas
Antiplatelet therapy with a P2Y12 inhibitor is a key component of treatment for patients with acute coronary syndromes undergoing percutaneous coronary intervention. Before the development of cangrelor (Kengreal, The Medicines Company, Parsippany, NJ), only oral P2Y12 inhibitors were available. Cangrelor is a reversible P2Y12 inhibitor that is administered as an intravenous infusion, and its quick onset and offset make it an appealing option for antiplatelet therapy, particularly for patients who are unable to take oral medications...
May 2017: Cardiology in Review
https://www.readbyqxmd.com/read/28377230/gpiib-iiia-receptor-inhibitors-in-acute-coronary-syndrome-patients-presenting-with-cardiogenic-shock-and-or-after-cardiopulmonary-resuscitation
#14
Vojko Kanic, Maja Vollrath, Meta Penko, Andrej Markota, Gregor Kompara, Zlatka Kanic
BACKGROUND: Data on the use of GPIIb-IIIa receptor inhibitors (GPI) in acute coronary syndrome (ACS) patients presenting with cardiogenic shock and/or after cardiopulmonary resuscitation is sparse. The aim of the study was to establish the possible influence of the adjunctive use of GPI on 30-day and 1-year mortality in these high-risk patients. METHODS: Acute coronary syndrome patients (261), who presented with cardiogenic shock and/or were cardiopulmonary resuscitated on admission, were analysed...
March 20, 2017: Heart, Lung & Circulation
https://www.readbyqxmd.com/read/28376544/how-long-does-it-take-clopidogrel-and-ticagrelor-to-inhibit-platelets-in-patients-undergoing-primary-percutaneous-coronary-intervention-a-detailed-pharmacodynamic-analysis-time-course-of-platelet-reactivity-in-stemi-tops
#15
Thomas O Bergmeijer, Thea C Godschalk, Paul W A Janssen, Kim van den Berge, Nicoline J Breet, Johannes C Kelder, Christian M Hackeng, Jurriën M Ten Berg
Antiplatelet therapy plays a pivotal role in patients with an ST-segment elevation myocardial infarction (STEMI) to prevent further atherothrombotic events, such as stent thrombosis. Although the risk of stent thrombosis is highest in the first hours after primary percutaneous coronary intervention (pPCI), little is known about when an adequate level of platelet inhibition is achieved following a clopidogrel or ticagrelor loading dose in STEMI patients. Patients presenting with STEMI in whom pPCI was performed and who were loaded with 600 mg clopidogrel or 180 mg ticagrelor were eligible for enrolment in this nonrandomized, open label, single-center study...
April 4, 2017: Seminars in Thrombosis and Hemostasis
https://www.readbyqxmd.com/read/28374678/incidence-and-outcome-of-switching-of-oral-platelet-p2y12-receptor-inhibitors-in-patients-with-acute-coronary-syndromes-undergoing-percutaneous-coronary-intervention-the-scope-registry
#16
Leonardo De Luca, Fabrizio D'Ascenzo, Giuseppe Musumeci, Francesco Saia, Guido Parodi, Ferdinando Varbella, Alfredo Marchese, Stefano De Servi, Sergio Berti, Leonardo Bolognese
AIMS: In patients with acute coronary syndromes (ACS) undergoing a percutaneous coronary intervention (PCI) switching of oral P2Y12 receptor inhibitors may frequently occur. METHODS AND RESULTS: The SCOPE registry was a multicenter, observational, prospective study aimed to evaluate the incidence and 1-month outcome of switching of oral P2Y12 receptor inhibitors in consecutive ACS patients undergoing PCI during a 3-month period. A total of 1363 consecutive patients have been enrolled in 39 PCI centers across Italy...
April 4, 2017: EuroIntervention
https://www.readbyqxmd.com/read/28362884/utility-of-the-aspirin-and-p2y12-response-assays-to-determine-the-effect-of-antiplatelet-agents-on-platelet-reactivity-in-traumatic-brain-injury
#17
Phillip V Parry, Phillip A Choi, Joshua S Bauer, David M Panczykowski, Ava M Puccio, David O Okonkwo
BACKGROUND: Premorbid antithrombotic medication may worsen intracranial injury and outcome after traumatic brain injury (TBI). Routine laboratory tests are insufficient to evaluate platelet activity. OBJECTIVE: To profile the spectrum of platelet inhibition, as measured by aspirin and P2Y12 response unit assays, in a TBI population on antiplatelet therapy. METHODS: This single-center, prospective cohort study included patients presenting to our institution between November 2010 and January 2015 with a clinical history of TBI...
January 1, 2017: Neurosurgery
https://www.readbyqxmd.com/read/28362883/use-of-aspirin-and-p2y12-response-assays-in-detecting-reversal-of-platelet-inhibition-with-platelet-transfusion-in-patients-with-traumatic-brain-injury-on-antiplatelet-therapy
#18
Phillip A Choi, Phillip V Parry, Joshua S Bauer, Benjamin E Zusman, David M Panczykowski, Ava M Puccio, David O Okonkwo
BACKGROUND: At present, guidelines are lacking on platelet transfusion in patients with a traumatic intracranial bleed and history of antiplatelet therapy. The aspirin and P2Y 12 response unit (ARU and PRU, respectively) assays detect the effect of aspirin and P2Y 12 inhibitors in the cardiac population. OBJECTIVE: To describe the reversal of platelet inhibition after platelet transfusion using the ARU and PRU assays in patients with traumatic brain injury. METHODS: Between 2010 and 2015, we conducted a prospective comparative cohort study of patients presenting with a positive head computed tomography and a history of antiplatelet therapy...
January 1, 2017: Neurosurgery
https://www.readbyqxmd.com/read/28358842/the-risk-of-clopidogrel-resistance-is-associated-with-abcb1-polymorphisms-but-not-promoter-methylation-in-a-chinese-han-population
#19
Jia Su, Qinglin Yu, Hao Zhu, Xiaojing Li, Hanbin Cui, Weiping Du, Lindan Ji, Maoqing Tong, Yibo Zheng, Hongyu Xu, Jianjiang Zhang, Yunyun Zhu, Yezi Xia, Ting Liu, Qi Yao, Jun Yang, Xiaomin Chen, Jingbo Yu
The goal of our study was to investigate the contribution of ABCB1 expression to the risk of clopidogrel resistance (CR). Platelets functions were measured using the Verify-Now P2Y12 assay. Applying Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP), the single-nucleotide polymorphisms (SNPs) was tested. Using bisulphite pyrosequencing assay, we investigated the association of the ABCB1 DNA methylation levels and CR. It was shown that female, hypertension, and lower albumin levels increased the risk of CR (P<0...
2017: PloS One
https://www.readbyqxmd.com/read/28356282/impact-of-diabetes-mellitus-on-the-pharmacodynamic-effects-of-ticagrelor-versus-clopidogrel-in-troponin-negative-acute-coronary-syndrome-patients-undergoing-ad-hoc-percutaneous-coronary-intervention
#20
Joseph M Sweeny, Dominick J Angiolillo, Francesco Franchi, Fabiana Rollini, Ron Waksman, Ganesh Raveendran, George Dangas, Naeem D Khan, Glenn F Carlson, Yonggang Zhao, Renli Teng, Roxana Mehran
BACKGROUND: Diabetes mellitus (DM) is associated with enhanced platelet reactivity and impaired response to oral antiplatelet therapy, including clopidogrel. This post hoc analysis investigated the pharmacodynamic effects of ticagrelor versus clopidogrel loading dose (LD) in troponin-negative acute coronary syndrome patients with or without DM undergoing percutaneous coronary intervention in the Ad Hoc PCI study. METHODS AND RESULTS: Patients randomized (1:1) to receive ticagrelor 180 mg LD or clopidogrel 600 mg LD were assessed by diabetic status...
March 29, 2017: Journal of the American Heart Association
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