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https://www.readbyqxmd.com/read/28921624/pharmacodynamics-and-pharmacokinetics-of-ticagrelor-versus-clopidogrel-in-patients-with-acute-coronary-syndromes-and-chronic-kidney-disease
#1
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
#2
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/28914344/influence-of-genetic-co-factors-on-the-population-pharmacokinetic-model-for-clopidogrel-and-its-active-thiol-metabolite
#3
Dorota Danielak, Marta Karaźniewicz-Łada, Anna Komosa, Paweł Burchardt, Maciej Lesiak, Łukasz Kruszyna, Agnieszka Graczyk-Szuster, Franciszek Główka
PURPOSE: A high interindividual variability is observed in the pharmacokinetics of clopidogrel, a widely used antiplatelet drug. In the present study, a joint parent-metabolite population pharmacokinetic model was developed to adequately describe observed concentrations of clopidogrel and its active thiol metabolite (H4). METHODS: The study included 63 patients undergoing elective coronarography or percutaneous coronary intervention. The population pharmacokinetic model was developed in the NONMEM 7...
September 15, 2017: European Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/28914074/impact-of-test-conditions-on-adp-induced-platelet-function-results-with-the-multiplate-assay-is-further-standardization-required
#4
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/28913918/clopidogrel-in-critically-ill-patients
#5
Christian Schoergenhofer, Eva-Luise Hobl, Peter Schellongowski, Gottfried Heinz, Walter Speidl, Jolanta Siller-Matula, Monika Schmid, Raute Sunder-Plaßmann, Thomas Stimpfl, Matthias Hackl, Bernd Jilma
Only limited data are available regarding the treatment of critically ill patients with clopidogrel. This trial investigated the effects and the drug concentrations of the CYP450 activated pro-drug clopidogrel (n=43) and the half-life of the similarly metabolized pantoprazole (n=16) in critically ill patients. ADP-induced aggregometry in whole blood classified 74% (95% confidence intervals 59-87%) of critically ill patients as poor responders (n=43), and 65% (49-79%) responded poorly according to the VASP-P assay...
September 15, 2017: Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/28906404/ticagrelor-induced-life-threatening-bleeding-via-the-cyclosporine-mediated-drug-interaction-a-case-report
#6
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/28906384/the-safety-and-efficacy-of-oral-anticoagulants-with-dual-versus-single-antiplatelet-therapy-in-patients-after-percutaneous-coronary-intervention-a-meta-analysis
#7
Jie Chen, Li-Yu Wang, Chao Deng, Xing-Hua Jiang, Tu-Gang Chen
BACKGROUND: A growing number of patients require oral anticoagulant (OAC) after undergoing percutaneous coronary intervention (PCI) with stent implantation due to the development of atrial fibrillation, but the optimal antithrombotic regimen remains controversial in these patients. METHODS: We systematically searched PUBMED, EMBASE, and CENTRAL from inception until September 2016 for randomized controlled trials or cohort studies that evaluated the comparative effects of TT versus DT...
September 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28904011/continuation-of-non-essential-medications-in-actively-dying-hospitalised-patients
#8
Beverly Rosa Williams, F Amos Bailey, Elizabeth Kvale, Neal Steil, Patricia S Goode, Richard E Kennedy, Kathryn L Burgio
OBJECTIVE: The objective of this analysis was to examine the use of 11 non-essential medications in actively dying patients. METHODS: This was a planned secondary analysis of data from the Best Practices for End-of-Life Care for Our Nation's Veterans trial, a multicentre implementation trial of an intervention to improve processes of end-of-life care in inpatient settings. Supported with an electronic comfort care decision support tool, intervention included training hospital staff to identify actively dying patients, communicate the prognosis to patients/families and implement best practices of traditionally home-based hospice care...
September 13, 2017: BMJ Supportive & Palliative Care
https://www.readbyqxmd.com/read/28902590/long-term-outcomes-of-patent-foramen-ovale-closure-or-medical-therapy-after-stroke
#9
Jeffrey L Saver, John D Carroll, David E Thaler, Richard W Smalling, Lee A MacDonald, David S Marks, David L Tirschwell
Background Whether closure of a patent foramen ovale reduces the risk of recurrence of ischemic stroke in patients who have had a cryptogenic ischemic stroke is unknown. Methods In a multicenter, randomized, open-label trial, with blinded adjudication of end-point events, we randomly assigned patients 18 to 60 years of age who had a patent foramen ovale (PFO) and had had a cryptogenic ischemic stroke to undergo closure of the PFO (PFO closure group) or to receive medical therapy alone (aspirin, warfarin, clopidogrel, or aspirin combined with extended-release dipyridamole; medical-therapy group)...
September 14, 2017: New England Journal of Medicine
https://www.readbyqxmd.com/read/28898876/filing-sources-after-oral-p2y12-platelet-inhibitors-to-the-food-and-drug-administration-adverse-event-reporting-system-faers
#10
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/28893489/review-of-aspirin-and-clopidogrel-resistance-in-peripheral-arterial-disease
#11
REVIEW
Mina Guirgis, Peter Thompson, Shirley Jansen
OBJECTIVE: Aspirin resistance (AR) and clopidogrel resistance (CR) are terms used to describe a reduction in the medication's efficacy in inhibiting platelet aggregation despite regular dosing. This review gives context to the clinical role and implications of antiplatelet resistance in peripheral arterial disease (PAD). METHODS: A review of English-language literature on AR and CR in PAD involving human subjects using PubMed and MEDLINE databases was performed in April 2017...
September 8, 2017: Journal of Vascular Surgery
https://www.readbyqxmd.com/read/28885524/iliac-vascular-injury-in-the-absence-of-a-pelvic-fracture
#12
Nancy Helton, Cathy McNeill, William Witham
This case study presents a rare iliac vascular injury in the absence of a pelvic fracture. A 36-year-old man sustained a blunt injury after being stuck by a motor vehicle. The only positive computed tomographic finding was in the pelvis that showed a 4 × 2-cm left retroperitoneal soft-tissue collection, appearing to encompass the left common and left external iliac veins. A pelvic venogram was obtained on Day 2 revealing a focal injury to the left external iliac vein with 60% narrowing. The patient was treated with clopidogrel and acetylsalicylic acid and discharged from the hospital to his home 3 days later...
September 2017: Journal of Trauma Nursing: the Official Journal of the Society of Trauma Nurses
https://www.readbyqxmd.com/read/28885323/pik3cg-single-nucleotide-polymorphisms-are-associated-with-poor-responsiveness-to-clopidogrel-and-increased-risk-of-ischemia-in-patients-with-coronary-heart-disease
#13
Ke-Cheng Li, Shu-Hong Yu, Bao-Zhong Zhuge
BACKGROUND: This study explores the associations between PIK3CG single nucleotide polymorphisms (SNPs, rs1129293 and rs17398575) and patient responsiveness to clopidogrel to evaluate the risks of ischemia in patients with coronary heart disease (CHD). METHODS: The study consisted of 513 CHD patients who received clopidogrel as part of antiplatelet therapy, after percutaneous coronary intervention. According to the patient responsiveness to clopidogrel, the subjects were assigned to either clopidogrel-resistant (CR) or clopidogrel-sensitive (CS) groups...
September 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28884095/hand-and-wrist-surgery-without-suspending-warfarin-or-oral-antiplatelet-systematic-review
#14
REVIEW
Trajano Sardenberg, Francisco Simões Deienno, Raffaello de Freitas Miranda, Denis Varanda, Andréa Christina Cortopassi, Paulo Roberto de Almeida Silvares
To assess, through a systematic literature review, whether or not it is necessary to suspend antithrombotic medications (warfarin, aspirin, and clopidogrel) to perform elective wrist and hand surgeries. The search for articles was performed using a combination of keywords in the databases available, without scientific design constraints, being selected series with five or more surgeries; the selected articles were analyzed regarding serious (need for surgical treatment) and mild complications (without surgery)...
June 2017: Revista Brasileira de Ortopedia
https://www.readbyqxmd.com/read/28883222/temporal-changes-in-platelet-response-in-acute-coronary-syndrome-patients-with-prasugrel-and-clopidogrel-after-stent-implantation
#15
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/28877643/a-case-series-of-18-patients-receiving-ticagrelor-after-carotid-stenting
#16
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/28877606/discordance-between-vasp-phosphorylation-and-platelet-aggregation-in-defining-high-on-clopidogrel-platelet-reactivity-after-st-segment-elevation-myocardial-infarction
#17
Jing Sun, Guo-Hong Yang, Jun-Xiang Liu, Xin-Lin Liu, Yong-Qiang Ma, Rui-Yi Lu, Ying-Ying Zhang, Shao-Bo Chen, Ji-Hong Zhao, Wen-Jie Ji, Xin Zhou, Yu-Ming Li
To investigate potential clinical characteristics associated with discordance between platelet vasodilator-stimulated phosphoprotein phosphorylation (VASP-P) flow cytometry (FCM) assay and light transmission aggregometry (LTA) in defining high on-clopidogrel platelet reactivity (HPR) after ST-segment elevation myocardial infarction (STEMI). In this study, platelet responsiveness was measured by the above 2 methods simultaneously on day 1 and on day 6 of STEMI onset in 90 consecutive patients who underwent primary percutaneous coronary intervention...
January 1, 2017: Clinical and Applied Thrombosis/hemostasis
https://www.readbyqxmd.com/read/28875522/developments-in-the-synthesis-of-the-antiplatelet-and-antithrombotic-drug-s-clopidogrel
#18
REVIEW
Aamer Saeed, Danish Shahzad, Muhammad Faisal, Fayaz Ali Larik, Hesham R El-Seedi, Pervaiz Ali Channar
S-(+)-Methyl 2-(2-chlorophenyl)-2-(6,7-dihydrothieno[3,2-c]pyridin-5(4H)-yl)acetate, also known as (S)-clopidogrel, is marketed under the trade names Plavix and Iscover. It is a potent thienopyridine-class of antithrombotic and antiplatelet drug (antiaggregant). Among the two available stereoisomers of clopidogrel, for pharmaceutical activities only the S-enantiomer is applicable, as no antithrombotic activity is observed in the R-enantiomer and causes political upheavals and social turmoil in animal experiments...
September 6, 2017: Chirality
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
#19
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
#20
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
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