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Cangrelor

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https://www.readbyqxmd.com/read/29036802/pharmacosimulation-of-interruptions-and-its-solution-in-intravenous-administration-of-cangrelor
#1
Maryna Masyuk, Nadia Heramvand, Johanna M Muessig, Amir M Nia, Amin Polzin, Markus Kollmann, Malte Kelm, Christian Jung
BACKGROUNDCangrelor is an intravenous adenosine diphosphate (ADP) P2Y12 receptor antagonist, which has to be administered as a bolus followed by immediate infusion. Nevertheless, in clinical routine deviations from the correct practice, such as delayed infusion onset or interruptions during infusion, may occur. OBJECTIVE: The objective of the present study was to investigate the impact of administration delays on cangrelor concentration in a pharmacological simulation setting and to give possible solutions for the clinical practice...
October 7, 2017: Clinical Hemorheology and Microcirculation
https://www.readbyqxmd.com/read/29030140/cangrelor-compared-with-clopidogrel-in-patients-with-prior-myocardial-infarction-insights-from-the-champion-trials
#2
Alon Eisen, Robert A Harrington, Gregg W Stone, Ph Gabriel Steg, C Michael Gibson, Christian W Hamm, Matthew J Price, Jayne Prats, Efthymios N Deliargyris, Kenneth W Mahaffey, Harvey D White, Deepak L Bhatt
BACKGROUND: Patients who have had a prior myocardial infarction (MI) are at increased risk for adverse outcomes after subsequent percutaneous coronary intervention (PCI). OBJECTIVE: The objective of this study is to examine the efficacy and safety of cangrelor, a potent intravenous P2Y12 inhibitor, in patients with prior MI. METHODS: Pooled data from the CHAMPION trials were examined. Prior MI was defined as a history of MI, excluding MI events at baseline...
October 5, 2017: International Journal of Cardiology
https://www.readbyqxmd.com/read/29022423/combination-antiplatelet-treatment-in-coronary-artery-disease-patients-a-necessary-evil-or-an-overzealous-practice
#3
Dimitrios Alexopoulos, Konstantinos Katogiannis, Danai Sfantou, John Lekakis
In seeking to improve care in coronary artery disease patients, further platelet inhibition has been occasionally applied beyond that provided by aspirin and a P2Y12 receptor antagonist. This review aims to offer insights about the rationale, the efficacy and safety of combination antiplatelet therapy, involving three or more agents. Overall, the use of glycoprotein (GP) IIb/IIIa inhibitors did not significantly modify the treatment effect of different antiplatelet strategies, including double vs standard clopidogrel, prasugrel vs clopidogrel, ticagrelor vs clopidogrel, cangrelor vs clopidogrel, and vorapaxar vs placebo...
October 12, 2017: Platelets
https://www.readbyqxmd.com/read/28928091/p2y12-antibody-inhibits-platelet-activity-and-protects-against-thrombogenesis
#4
Nicole R Hensch, Zubair A Karim, Joshua Pineda, Nicole Mercado, Fatima Z Alshbool, Fadi T Khasawneh
Given that platelet hyperactivity is known to give rise to thrombotic disorders, new and/or novel antiplatelet therapies are constantly being developed to add to, or to complement the current arsenal of agents. To this end, adenosine diphosphate (ADP) is an important platelet activator that acts by binding to the G-protein coupled P2Y1 and P2Y12 receptors. Although the contribution of the P2Y12 receptor to the genesis of thrombosis is well established, the parenteral arsenal of drugs targeting this receptor in clinical use is limited to cangrelor...
November 18, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28844201/bivalirudin-versus-heparin-monotherapy-in-myocardial-infarction
#5
RANDOMIZED CONTROLLED TRIAL
David Erlinge, Elmir Omerovic, Ole Fröbert, Rikard Linder, Mikael Danielewicz, Mehmet Hamid, Eva Swahn, Loghman Henareh, Henrik Wagner, Peter Hårdhammar, Iwar Sjögren, Jason Stewart, Per Grimfjärd, Jens Jensen, Mikael Aasa, Lotta Robertsson, Pontus Lindroos, Jan Haupt, Helena Wikström, Anders Ulvenstam, Pallonji Bhiladvala, Bo Lindvall, Anders Lundin, Tim Tödt, Dan Ioanes, Truls Råmunddal, Thomas Kellerth, Leszek Zagozdzon, Matthias Götberg, Jonas Andersson, Oskar Angerås, Ollie Östlund, Bo Lagerqvist, Claes Held, Lars Wallentin, Fredrik Scherstén, Peter Eriksson, Sasha Koul, Stefan James
BACKGROUND: The comparative efficacy of various anticoagulation strategies has not been clearly established in patients with acute myocardial infarction who are undergoing percutaneous coronary intervention (PCI) according to current practice, which includes the use of radial-artery access for PCI and administration of potent P2Y12 inhibitors without the planned use of glycoprotein IIb/IIIa inhibitors. METHODS: In this multicenter, randomized, registry-based, open-label clinical trial, we enrolled patients with either ST-segment elevation myocardial infarction (STEMI) or non-STEMI (NSTEMI) who were undergoing PCI and receiving treatment with a potent P2Y12 inhibitor (ticagrelor, prasugrel, or cangrelor) without the planned use of glycoprotein IIb/IIIa inhibitors...
September 21, 2017: New England Journal of Medicine
https://www.readbyqxmd.com/read/28802512/cangrelor-versus-clopidogrel-on-a-background-of-unfractionated-heparin-from-champion-phoenix
#6
RANDOMIZED CONTROLLED TRIAL
Muthiah Vaduganathan, Robert A Harrington, Gregg W Stone, Ph Gabriel Steg, C Michael Gibson, Christian W Hamm, Matthew J Price, Efthymios N Deliargyris, Jayne Prats, Kenneth W Mahaffey, Harvey D White, Deepak L Bhatt
Cangrelor is approved for use during percutaneous coronary intervention (PCI) and is administered with different parenteral anticoagulants. We examined the efficacy and safety of cangrelor in the subgroup of patients who received unfractionated heparin (UFH) during PCI in the modified intention-to-treat population of the randomized CHAMPION PHOENIX trial (cangrelor vs clopidogrel; n = 10,939). The primary efficacy end point was the composite of death, myocardial infarction, ischemia-driven revascularization, or stent thrombosis (ST) at 48 hours...
October 1, 2017: American Journal of Cardiology
https://www.readbyqxmd.com/read/28801539/cangrelor-in-older-patients-undergoing-percutaneous-coronary-intervention-findings-from-champion-phoenix
#7
Matthew A Cavender, Deepak L Bhatt, Gregg W Stone, Ph Gabriel Steg, C Michael Gibson, Christian W Hamm, Matthew J Price, Jayne Prats, Steven Elkin, Efthymios N Deliargyris, Kenneth W Mahaffey, Harvey D White, Robert A Harrington
BACKGROUND: Older patients treated with percutaneous coronary intervention are at increased risk of periprocedural events. METHODS AND RESULTS: CHAMPION (cangrelor versus standard therapy to achieve optimal management of platelet inhibition) PHOENIX randomized 11 145 patients to cangrelor or clopidogrel. We sought to determine the outcomes in the prespecified subgroup of patients ≥75 years old (n=2010; 18%). Cangrelor resulted in directionally consistent effects on the primary end point (death, myocardial infarction, ischemia-driven revascularization, or stent thrombosis) in patients ≥75 years old (odds ratio [OR], 0...
August 2017: Circulation. Cardiovascular Interventions
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
#8
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)...
2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28693931/maintenance-of-drug-eluting-stent-patency-through-use-of-a-cangrelor-infusion-in-the-clinical-setting-of-massive-pulmonary-hemorrhage-and-venoarterial-extracorporeal-membrane-oxygenation
#9
Troy G Seelhammer, Erica D Wittwer, Scott D Nei, James Skiba
No abstract text is available yet for this article.
March 24, 2017: Journal of Cardiothoracic and Vascular Anesthesia
https://www.readbyqxmd.com/read/28637879/platelets-express-activated-p2y12-receptor-in-patients-with-diabetes-mellitus
#10
Liang Hu, Lin Chang, Yan Zhang, Lili Zhai, Shenghui Zhang, Zhiyong Qi, Hongmei Yan, Yan Yan, Xinping Luo, Si Zhang, Yiping Wang, Satya P Kunapuli, Hongying Ye, Zhongren Ding
BACKGROUND: Platelets from patients with diabetes mellitus are hyperactive. Hyperactivated platelets may contribute to cardiovascular complications and inadequate responses to antiplatelet agents in the setting of diabetes mellitus. However, the underlying mechanism of hyperactivated platelets is not completely understood. METHODS: We measured P2Y12 expression on platelets from patients with type 2 diabetes mellitus and on platelets from rats with diabetes mellitus...
August 29, 2017: Circulation
https://www.readbyqxmd.com/read/28612420/bivalirudin-or-heparin-for-radial-access
#11
EDITORIAL
John A Bittl
Bivalirudin is a reasonable choice during transradial PCI for acute MI when bleeding risk is high and clopidogrel or cangrelor is used Heparin is reasonable during transradial PCI when bleeding risk is low and high-intensity antiplatelet therapy is used Future studies are required to define the utility of post-PCI bivalirudin infusions.
June 1, 2017: Catheterization and Cardiovascular Interventions
https://www.readbyqxmd.com/read/28577670/cangrelor-reduces-the-risk-of-ischemic-complications-in-patients-with-single-vessel-and-multi-vessel-disease-undergoing-percutaneous-coronary-intervention-insights-from-the-champion-phoenix-trial
#12
RANDOMIZED CONTROLLED TRIAL
Freddy Abnousi, Vandana Sundaram, Celina M Yong, Jayne Prats, Efthymios N Deliargyris, Gregg W Stone, Christian W Hamm, Philippe Gabriel Steg, Charles Michael Gibson, Harvey D White, Matthew J Price, Philippe Généreux, Manisha Desai, Lingyao Yang, Victoria Y Ding, Robert A Harrington, Deepak L Bhatt, Kenneth W Mahaffey
OBJECTIVE: To examine the safety and efficacy of cangrelor in patients with single-vessel disease (SVD) and multi-vessel disease (MVD). BACKGROUND: Cangrelor, an intravenous, rapidly acting P2Y12 inhibitor, is superior to clopidogrel in reducing ischemic events among patients receiving percutaneous coronary intervention (PCI). METHODS: We studied a modified intention to treat population of patients with SVD and MVD from the CHAMPION PHOENIX trial...
June 2017: American Heart Journal
https://www.readbyqxmd.com/read/28576266/safety-and-tolerability-of-transitioning-from-cangrelor-to-ticagrelor-in-patients-who-underwent-percutaneous-coronary-intervention
#13
Hisham A Badreldin, Danielle Carter, Bryan M Cook, Arman Qamar, Muthiah Vaduganathan, Deepak L Bhatt
The 3 phase 3 CHAMPION (Cangrelor vs Standard Therapy to Achieve Optimal Management of Platelet Inhibition) trials collectively demonstrated the safety of transitioning from cangrelor, a potent, parenteral rapidly-acting P2Y12 inhibitor, to clopidogrel in patients who underwent percutaneous coronary intervention (PCI). However, variation in timing of therapy, site-specific binding, and drug half-lives may theoretically complicate switching to other oral P2Y12 inhibitors. Since regulatory approval, limited data are available regarding the "real-world" safety and tolerability of transitioning to these more potent oral P2Y12 antagonists...
August 1, 2017: American Journal of Cardiology
https://www.readbyqxmd.com/read/28574274/practical-considerations-for-cangrelor-use-in-patients-with-acute-coronary-syndromes
#14
Sergio Leonardi, Deepak L Bhatt
Cangrelor, the first and currently only available intravenous P2Y12 receptor antagonist, has been approved and is now being used in patients with coronary artery disease requiring percutaneous coronary intervention. The rationale for cangrelor use is most robust in patients requiring an immediate, profound, and predictable level of P2Y12 inhibition - especially in patients with acute coronary syndromes. Herein we summarize the drug development program and reflect on practical considerations for clinicians on cangrelor use in the acute setting surrounding percutaneous coronary intervention, including selection of patients, concomitant administration of glycoprotein IIb/IIIa inhibitors and transition strategies from intravenous to oral P2Y12 receptor antagonists...
June 1, 2017: European Heart Journal. Acute Cardiovascular Care
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
#15
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/28382371/characteristics-of-dyspnoea-and-associated-clinical-outcomes-in-the-champion-phoenix-study
#16
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...
June 2, 2017: Thrombosis and Haemostasis
https://www.readbyqxmd.com/read/28379902/cangrelor-a-new-route-for-p2y12-inhibition
#17
REVIEW
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/28345287/contribution-of-platelet-p2y12-receptors-to-chronic-complete-freund-s-adjuvant-induced-inflammatory-pain
#18
K Bekő, B Koványi, F Gölöncsér, G Horváth, Á Dénes, Z Környei, B Botz, Z Helyes, C E Müller, B Sperlágh
Essentials The role of platelet P2Y12 receptors in the regulation of chronic inflammatory pain is unknown. Complete Freund's Adjuvant (CFA)-induced chronic inflammatory pain model was used in mice. Gene deficiency and antagonists of P2Y12 receptors attenuate hyperalgesia and local inflammation. Platelet P2Y12 receptors contribute to these effects in the chronic phase of inflammation. SUMMARY: Background P2Y12 receptor antagonists are widely used in clinical practice to inhibit platelet aggregation...
June 2017: Journal of Thrombosis and Haemostasis: JTH
https://www.readbyqxmd.com/read/28335837/potent-p2y12-inhibitors-in-men%C3%A2-versus%C3%A2-women-a%C3%A2-collaborative%C3%A2-meta-analysis%C3%A2-of%C3%A2-randomized%C3%A2-trials
#19
COMPARATIVE STUDY
Emily S Lau, Eugene Braunwald, Sabina A Murphy, Stephen D Wiviott, Marc P Bonaca, Steen Husted, Stefan K James, Lars Wallentin, Peter Clemmensen, Matthew T Roe, E Magnus Ohman, Robert A Harrington, Jessica L Mega, Deepak L Bhatt, Marc S Sabatine, Michelle L O'Donoghue
BACKGROUND: Sex-specific differences in response to antiplatelet therapies have been described. Whether women and men derive comparable benefit from intensification of antiplatelet therapy remains uncertain. OBJECTIVES: The study investigated the efficacy and safety of the potent P2Y12 inhibitors in patients with coronary artery disease. METHODS: A collaborative sex-specific meta-analysis was conducted of phase III or IV randomized trials of potent P2Y12 inhibitors, including prasugrel, ticagrelor, and intravenous cangrelor...
March 28, 2017: Journal of the American College of Cardiology
https://www.readbyqxmd.com/read/28296036/targeting-of-c-type-lectin-like-receptor%C3%A2-2-or-p2y12-for-the-prevention-of-platelet-activation-by-immunotherapeutic-cpg-oligodeoxynucleotides
#20
C Delierneux, N Donis, L Servais, O Wéra, C Lecut, M Vandereyken, L Musumeci, S Rahmouni, J Schneider, J A Eble, P Lancellotti, C Oury
Essentials CpG oligodeoxynucleotide (ODN) immuotherapeutics cause undesired platelet activating effects. It is crucial to understand the mechanisms of these effects to identify protective strategies. CpG ODN-induced platelet activation depends on C-type lectin-like receptor 2 (CLEC-2) and P2Y12. Targeting CLEC-2 or P2Y12 fully prevents CpG ODN-induced platelet activation and thrombosis. SUMMARY: Background Synthetic phosphorothioate-modified CpG oligodeoxynucleotides (ODNs) show potent immunostimulatory properties that are widely exploited in clinical trials of anticancer treatment...
May 2017: Journal of Thrombosis and Haemostasis: JTH
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