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Otavio Berwanger, Jose C Nicolau, Antonio C Carvalho, Lixin Jiang, Shaun Goodman, Stephen J Nicholls, Alexander Parkhomenko, Oleg Averkov, Carlos Tajer, Germán Malaga, Jose F Kerr Saraiva, Francisco Fonseca, Helio P Guimaraes, Pedro G M de Barros E Silva, Lucas P Damiani, Denise M Paisani, Camila M R Lasagno, Carolina T Candido, Nanci Valeis, Diogo D F Moia, Leopoldo S Piegas, Christopher B Granger, Harvey White, Renato D Lopes
BACKGROUND: The safety and efficacy of ticagrelor in patients with ST-elevation myocardial infarction (STEMI) treated with fibrinolytic therapy remain uncertain. OBJECTIVES: The primary objective of the TicagRElor in pAtients with ST elevation myocardial infarction treated with Thrombolysis (TREAT) trial is to evaluate the short-term safety of ticagrelor when compared with clopidogrel in STEMI patients treated with fibrinolytic therapy. Key secondary objectives are to assess the safety and efficacy of ticagrelor compared with clopidogrel at 12-months...
March 3, 2018: American Heart Journal
Byambasuren Ganbaatar, Daiju Fukuda, Hotimah Masdan Salim, Sachiko Nishimoto, Kimie Tanaka, Yasutomi Higashikuni, Yoichiro Hirata, Shusuke Yagi, Takeshi Soeki, Masataka Sata
BACKGROUND AND AIMS: Ticagrelor reduces cardiovascular events in patients with acute coronary syndrome (ACS). Recent studies demonstrated the expression of P2Y12 on vascular cells including endothelial cells, as well as platelets, and suggested its contribution to atherogenesis. We investigated whether ticagrelor attenuates vascular dysfunction and inhibits atherogenesis in apolipoprotein E-deficient (apoe-/- ) mice. METHODS: Eight-week-old male apoe-/- mice were fed a western-type diet (WTD) supplemented with 0...
May 31, 2018: Atherosclerosis
Renee Koski, Blake Kennedy
Current practice guidelines recommend dual antiplatelet therapy comprised of aspirin and a purinergic signaling receptor Y12 (P2Y12 ) for patients following acute coronary syndrome. This article compares the efficacy, safety, and other characteristics of the three available oral P2Y12 inhibitors-clopidogrel, prasugrel, and ticagrelor.
June 2018: P & T: a Peer-reviewed Journal for Formulary Management
WenHua Li, SongQi Guo, Shu Wang, Xin Sun, ZhuQin Li, XinYong Sun, YanMing Sun, LanFeng Wang, Wei Pan
PURPOSE: This study aimed to explore the effects of ticagrelor (a P2Y12 receptor inhibitor) on interleukin (IL)-17 and myeloperoxidase (MPO) expression in coronary thrombus as well as on the coronary blood flow in ST-segment elevation myocardial infarction (STEMI) patients following percutaneous coronary intervention (PCI). METHODS: Forty STEMI patients who were admitted to the First Affiliated Hospital of Harbin Medical University between August 1, 2014 and December 30, 2014 were enrolled in this study according to a set inclusion criteria...
2018: Journal of Pharmacy & Pharmaceutical Sciences: a Publication of the Canadian Society for Pharmaceutical Sciences
José C Nicolau, Luciano M Baracioli, Robert P Giugliano
Cardiovascular disease (CVD) is the main cause of death in the world. Coronary artery disease (CAD) is the most common form of CVD presentation, but the prevalence of peripheral artery disease (PAD) is increasing. Patients with polyvascular disease comprise a very high-risk population that has been infrequently studied. Areas covered: The authors review the current evidence of the efficacy and safety of ticagrelor in the setting of acute coronary syndrome and stable patients post-MI with and without PAD and summarize its pharmacokinetics, pharmacodynamics, and regulatory issues...
June 12, 2018: Expert Opinion on Pharmacotherapy
Théo Willeman, Raphael Marlu, Holger Böhle, Gilles Francony, Jean-François Jourdil, Xavier Fonrose, Françoise Stanke-Labesque
BACKGROUND: Ticagrelor is a direct and reversible competitive antagonist of the P2Y12 receptor and inhibits platelet activation. Although adverse bleeding is common, fatal intoxication has never been documented. CASE DESCRIPTION: A 47-year-old man died from a severe cerebral hemorrhage secondary to a fall and cranial trauma 4 d after the massive intake of ticagrelor. Iterative platelet transfusions did not improve his condition. Toxicological analyses by liquid chromatography tandem mass spectrometry (LC-MS/MS) revealed high plasma concentrations of ticagrelor (3343 µg/L) and its active metabolite AR-C124910XX (656 µg/L) 10 h after intake...
June 11, 2018: Clinical Toxicology
Sukhdeep S Basra, Tracy Y Wang, DaJuanicia N Simon, Karen Chiswell, Salim S Virani, Mahboob Alam, Vijay Nambi, Ali E Denktas, Anita Deswal, Biykem Bozkurt, Christie M Ballantyne, Eric D Peterson, Hani Jneid
BACKGROUND: Ticagrelor is a P2Y12 receptor inhibitor with superior clinical efficacy compared with clopidogrel. However, it is associated with reduced efficacy when combined with a high-dose aspirin. METHODS AND RESULTS: Patients in the acute coronary treatment and intervention outcomes network (ACTION) Registry-Get With The Guidelines (GWTG) with acute myocardial infarction from October 2013 through December 2014 were included in the study (167 455 patients; 622 sites)...
June 9, 2018: Journal of the American Heart Association
Uwe Zeymer, Martin Cully, Mathias Hochadel
Aims: Little is known about the adherence to dual antiplatelet therapy with ticagrelor and reasons for discontinuation in real ife. Therefore we evaluated the 12-month course of patients with acute coronary syndromes (ACS) treated with percutaneous coronary intervention (PCI) and ticagrelor during the acute phase. Methods and results: A total of 614 patients included into the prospective ALKK-PCI Registry between 2014 and 2015 surviving for at least 12 months after discharge provided informations about duration of ticagrelor therapy...
June 7, 2018: European Heart Journal. Cardiovascular Pharmacotherapy
Wael Sumaya, William A E Parker, Rebekah Fretwell, Ian R Hall, David S Barmby, James D Richardson, Javaid Iqbal, Zulfiquar Adam, Kenneth P Morgan, Julian P Gunn, Annah E Mason, Heather M Judge, Christopher P Gale, Ramzi A Ajjan, Robert F Storey
Delayed onset of action of oral P2Y12 inhibitors in ST-elevation myocardial infarction (STEMI) patients may increase the risk of acute stent thrombosis. Available parenteral anti-thrombotic strategies, to deal with this issue, are limited by added cost and increased risk of bleeding. We investigated the pharmacodynamic effects of a novel regimen of enoxaparin in STEMI patients undergoing primary percutaneous coronary intervention (PPCI). Twenty patients were recruited to receive 0.75 mg/kg bolus of enoxaparin (pre-PPCI) followed by infusion of enoxaparin 0...
June 6, 2018: Thrombosis and Haemostasis
Sasha Koul, J Gustav Smith, Matthias Götberg, Elmir Omerovic, Joakim Alfredsson, Dimitrios Venetsanos, Jonas Persson, Jens Jensen, Bo Lagerqvist, Björn Redfors, Stefan James, David Erlinge
BACKGROUND: The effects of ticagrelor pretreatment in patients with ST-segment-elevation myocardial infarction undergoing primary percutaneous coronary intervention (PCI) is debated. This study investigated the effects of ticagrelor pretreatment on clinical outcomes in this patient group. METHODS AND RESULTS: Patients with ST-segment-elevation myocardial infarction undergoing primary PCI were included from October 2010 to October 2014 in Sweden. Screening was done using the SWEDEHEART register (Swedish Web-System for Enhancement and Development of Evidence-Based Care in Heart Disease Evaluated According to Recommended Therapies)...
March 2018: Circulation. Cardiovascular Interventions
Kathryn E Hally, Anne C La Flamme, Scott A Harding, Peter D Larsen
Platelet activation underlies the pathology of an acute myocardial infarction (AMI), and dual antiplatelet therapy (DAPT) is administered post-AMI to limit this activation. Platelets express Toll-like receptors (TLRs) 1, 2, and 4 and become potently activated in response to TLR2/1 and TLR4 stimulation. However, it is unknown whether antiplatelet agents can protect against platelet activation via these TLR pathways. This study aimed to determine the extent to which TLR-mediated platelet activation can be inhibited by currently used antiplatelet agents...
June 5, 2018: Platelets
Choongki Kim, Byeong Keuk Kim, Sung Jin Hong, Chul Min Ahn, Jung Sun Kim, Young Guk Ko, Donghoon Choi, Myeong Ki Hong, Yangsoo Jang
PURPOSE: This study aimed to compare the effects of ticagrelor and clopidogrel on early neointimal healing assessed with optical coherence tomography (OCT) after drug-eluting stent (DES) implantation in patients with acute myocardial infarction (AMI). MATERIALS AND METHODS: AMI patients were randomly assigned to either the ticagrelor or clopidogrel arm. After DES implantation, OCT was performed to assess the percentages of uncovered struts immediately after procedure and 3 months later...
July 2018: Yonsei Medical Journal
Fabian Stimpfle, Maike Bauer, Dominik Rath, Elke Schaeffeler, Matthias Schwab, Meinrad Gawaz, Stefan Winter, Tobias Geisler
Introduction: Platelet endothelial aggregation receptor 1 (PEAR1) triggers platelet aggregation and is expressed in platelets and endothelial cells. Genome-wide association studies (GWAS) showed an association between platelet function and single-nucleotide polymorphisms (SNPs) in PEAR1 . Methods: In 582 consecutive patients with stable coronary artery disease (CAD) or acute coronary syndrome (ACS) scheduled for PCI and treated with ASA and Clopidogrel, Prasugrel, or Ticagrelor, SNP analysis for rs12566888, rs2768759, rs41273215, rs3737224, and rs822442 was performed...
2018: Frontiers in Pharmacology
Pei Zhu, Xiaofang Tang, Jingjing Xu, Ying Song, Ru Liu, Yin Zhang, Lijian Gao, Zhan Gao, Jue Chen, Yuejin Yang, Runlin Gao, Bo Xu, Jinqing Yuan
AIM: To evaluate the incidence, predictors and outcomes of post-discharge gastrointestinal bleeding (GIB) in patients underwent percutaneous coronary intervention (PCI) in a 2-year follow-up study. METHODS AND RESULTS: All consecutive patients who underwent PCI throughout 2013 were enrolled. Multivariable cox proportional hazards regression were used to identify predictors of post-discharge GIB and two year major adverse cardiovascular and cerebrovascular events (MACCE)...
June 4, 2018: Cardiovascular Therapeutics
Benjamin M Scirica, Sameer Bansilal, Farideh Davoudi, Paul W Armstrong, Robert M Clare, Phillip J Schulte, Karen S Pieper, Richard C Becker, Stefan K James, Robert F Storey, Philippe Gabriel Steg, Claes Held, Anders Himmelmann, Kenneth W Mahaffey, Lars Wallentin, Christopher P Cannon
BACKGROUND: Although bradyarrhythmias have been observed with ticagrelor and its use with advanced atrioventricular block is not recommended, questions arise regarding its use in patients with mild conduction abnormalities. The objectives were to compare rates of clinically relevant arrhythmias in relation to any mild baseline conduction abnormality in patients with acute coronary syndrome randomized to ticagrelor versus clopidogrel. METHODS: We included all subjects in the electrocardiographic (ECG) substudy of the Platelet Inhibition and Patient Outcomes trial, excluding those with missing baseline ECG or with a pacemaker at baseline (N = 15,460)...
May 7, 2018: American Heart Journal
William A E Parker, Niclas Eriksson, Richard C Becker, Deepak Voora, Axel Åkerblom, Anders Himmelmann, Stefan K James, Lars Wallentin, Robert F Storey
In the PLATelet inhibition and patient Outcomes (PLATO) study, the P2Y12 inhibitors ticagrelor and clopidogrel were compared in the treatment of acute coronary syndromes (ACS). Ticagrelor was shown to reduce occurrence of the primary end point - a composite of death from vascular causes, myocardial infarction, or stroke - compared to clopidogrel. Ticagrelor's pleiotropic effects on reuptake of adenosine via inhibition of equilibrative nucleoside transporter 1 (ENT1) have been hypothesized to contribute to this...
May 31, 2018: Platelets
Renli Teng, Sharen Muldowney, Yonggang Zhao, Jolene Kay Berg, Jonathan Lu, Naeem D Khan
PURPOSE: This single-dose, randomized, open-label, parallel-group, and crossover study assessed pharmacokinetics (PK), pharmacodynamics (PD), and safety of ticagrelor in subjects on hemodialysis versus healthy subjects. METHODS: Hemodialysis subjects were randomized, receiving a single ticagrelor 90-mg dose 1 day post-hemodialysis or just before hemodialysis, with an intervening washout of ≥ 7 days. Healthy subjects (creatinine clearance ≥ 90 mL/min) received a single ticagrelor 90-mg dose...
May 30, 2018: European Journal of Clinical Pharmacology
Xiaoye Li, Ying Xue, Hongyi Wu
Purpose: To report a case of atrioventricular block (AVB) which might be associated with the right coronary artery lesion and the novel oral antithrombotic drug ticagrelor mediated by the increasing adenosine plasma concentration (APC). Case Report: A 65-year-old man was given loading dose of ticagrelor (180 mg) before coronary angiography with total thrombotic occlusion of right coronary artery and one stent was implanted. On second day after successful percutaneous coronary intervention, ECG monitoring showed second-degree (Mobitz type I) AVB with prolonged PR interval (299 ms)...
2018: Case Reports in Vascular Medicine
Starr-Mar'ee C Bedy, Jacob P Kesterson, Greg Flaker
A 65-year-old Caucasian man was hospitalized for a non-ST-elevation myocardial infarction. On discharge, the patient was started on multiple new medications, including clopidogrel and atorvastatin. Twenty-six days after discharge, he presented to the Emergency Department (ED) with polyarthralgias. He was instructed to stop atorvastatin and to follow up with rheumatology and cardiology clinic. At cardiology clinic follow-up 43 days after ED discharge, clopidogrel was discontinued and patient was switched to ticagrelor...
2018: Case Reports in Emergency Medicine
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