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antiplatelet pharmacogenetics

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https://www.readbyqxmd.com/read/29738309/pharmacogenetic-testing-by-polymorphic-markers-681g-a-and-636g-a-cyp2c19-gene-in-patients-with-acute-coronary-syndrome-and-gastric-ulcer-in-the-republic-of-sakha-yakutia
#1
Denis S Fedorinov, Karin B Mirzaev, Dmitriy V Ivashchenko, Ilyas I Temirbulatov, Dmitriy A Sychev, Nadezda R Maksimova, Jana V Chertovskih, Nyurguiana V Popova, Ksenia S Tayurskaya, Zoya A Rudykh
BACKGROUND: The focus of the study is to determine the prevalence of CYP2C19 alleles, associated with the risk of changes in the pharmacological response to clopidogrel and proton pump inhibitors in patients with acute coronary syndrome (ACS) and gastric ulcer from Russian and Yakut ethnic groups. METHODS: The research included 411 patients with ACS (143 Russians and 268 Yakuts) and 204 patients with histologically confirmed gastric ulcer (63 Russians and 141 Yakuts)...
May 8, 2018: Drug Metabolism and Personalized Therapy
https://www.readbyqxmd.com/read/29520080/impact-of-cyp2c19-polymorphism-in-prognosis-of-minor-stroke-or-tia-patients-with-declined-egfr-on-dual-antiplatelet-therapy-chance-substudy
#2
Yu Wu, Yilun Zhou, Yuesong Pan, Xingquan Zhao, Liping Liu, David Wang, Chunxue Wang, Hao Li, S Claiborne Johnston, Xia Meng, Yilong Wang, Yongjun Wang
Clopidogrel resistance is prevalent in chronic kidney disease (CKD) patients. Genetic polymorphism is considered to be the most important factor that influences clopidogrel resistance. Limited data exist as to the role of pharmacogenetics in prognosis of stroke patients with impaired renal function on clopidogrel. We sought to explore whether decreased kidney function alters the association between CYP2C19 genetic variants and clinical outcome in patients with minor stroke or transient ischemic attack (TIA) receiving clopidogrel therapy...
March 8, 2018: Pharmacogenomics Journal
https://www.readbyqxmd.com/read/29412111/efficacy-of-p2y12-receptor-blockers-after-myocardial-infarction-and-genetic-variability-of-their-metabolic-pathways
#3
Jan Machal, Ota Hlinomaz
BACKGROUND: Various antiplatelet drugs are used following acute coronary syndromes (ACS). Of them, adenosine diphosphate receptor P2Y12 inhibitors clopidogrel, prasugrel and ticagrelor are currently used for post-ACS long-term treatment. Although they act on the same receptor, they differ in pharmacodynamics and pharmacokinetics. Several enzymes and transporters involved in the metabolism of P2Y12 inhibitors show genetic variability with functional impact. This includes P-glycoprotein, carboxylesterase 1 and, most notably, CYP2C19 that is important in clopidogrel activation...
February 5, 2018: Current Vascular Pharmacology
https://www.readbyqxmd.com/read/29280403/ticagrelor-in-modern-cardiology-an-up-to-date-review-of-most-important-aspects-of-ticagrelor-pharmacotherapy
#4
REVIEW
Dorota Danielak, Marta Karaźniewicz-Łada, Franciszek Główka
Ticagrelor is a first drug of a new chemical class cyclopentyltriazolopyrimidines. It is an antiplatelet agent with a unique mechanism of action, allowing a direct and reversible competitive inhibition of P2Y12 receptor. According to newest guidelines, it is recommended for prevention of thrombotic events in patients with acute coronary syndromes. Moreover, it is preferred over clopidogrel, an older generation antiplatelet drug, and therefore gains more interest in modern cardiology and vascular medicine. Areas covered: This review is a comprehensive and thorough summary of the most important findings on ticagrelor...
February 2018: Expert Opinion on Pharmacotherapy
https://www.readbyqxmd.com/read/29138287/clopidogrel-carboxylic-acid-glucuronidation-is-mediated-mainly-by-ugt2b7-ugt2b4-and-ugt2b17-implications-for-pharmacogenetics-and-drug-drug-interactions
#5
Helinä Kahma, Anne M Filppula, Mikko Neuvonen, E Katriina Tarkiainen, Aleksi Tornio, Mikko T Holmberg, Matti K Itkonen, Moshe Finel, Pertti J Neuvonen, Mikko Niemi, Janne T Backman
The antiplatelet drug clopidogrel is metabolized to an acyl- β -d-glucuronide, which causes time-dependent inactivation of CYP2C8. Our aim was to characterize the UDP-glucuronosyltransferase (UGT) enzymes that are responsible for the formation of clopidogrel acyl- β -d-glucuronide. Kinetic analyses and targeted inhibition experiments were performed using pooled human liver and intestine microsomes (HLMs and HIMs, respectively) and selected human recombinant UGTs based on preliminary screening. The effects of relevant UGT polymorphisms on the pharmacokinetics of clopidogrel were evaluated in 106 healthy volunteers...
February 2018: Drug Metabolism and Disposition: the Biological Fate of Chemicals
https://www.readbyqxmd.com/read/29103068/antiplatelet-therapy-for-secondary-prevention-of-vascular-disease-complications
#6
REVIEW
Rahul R Goli, Mayur M Contractor, Ashwin Nathan, Sony Tuteja, Taisei Kobayashi, Jay Giri
PURPOSE OF REVIEW: Platelets are activated upon interaction with injured vascular endothelium to form a primary hemostatic plug. Pathogenic thrombosis driven by platelet aggregation can occur in the setting of vascular disease leading to ischemic events. The use of antiplatelet agents has become a mainstay for prevention of the secondary complications of vascular disease. This review summarizes seminal and recent literature related to this area. RECENT FINDINGS: Aspirin is a cornerstone of antiplatelet therapy for coronary artery disease and cerebrovascular disease for prevention of myocardial infarction, stroke, and vascular death...
November 4, 2017: Current Atherosclerosis Reports
https://www.readbyqxmd.com/read/28690699/feasibility-of-clinical-pharmacist-led-cyp2c19-genotyping-for-patients-receiving-non-emergent-cardiac-catheterization-in-an-integrated-health-system
#7
Samuel G Johnson, Paul B Shaw, Thomas Delate, Deanna L Kurz, Dylon Gregg, John C Darnell, Christina L Aquilante
OBJECTIVE: To assess the feasibility of clinical pharmacist-led CYP2C19 genotype-guided P2Y12 inhibitor antiplatelet drug therapy recommendations to cardiologists in an outpatient cardiology practice. METHODS: This was a prospective, open-labeled, single-arm study conducted in an integrated healthcare delivery system between March 1, 2013 and January 23, 2014. Patients requiring non-emergent cardiac catheterization were included. A clinical pharmacist provided interpretation and recommendations from genotyping results...
April 2017: Pharmacy Practice
https://www.readbyqxmd.com/read/28571507/the-genetic-basis-of-antiplatelet-and-anticoagulant-therapy-a-pharmacogenetic-review-of-newer-antiplatelets-clopidogrel-prasugrel-and-ticagrelor-and-anticoagulants-dabigatran-rivaroxaban-apixaban-and-edoxaban
#8
REVIEW
Cormac T O'connor, Thomas J Kiernan, Bryan P Yan
The study of pharmacogenomics presents the possibility of individualised optimisation of drug therapy tailored to each patients' unique physiological traits. Both antiplatelet and anticoagulant drugs play a key role in the management of cardiovascular disease. Despite their importance, there is a substantial volume of literature to suggest marked person-to-person variability in their effect. Areas covered: This article reviews the data available for the genetic cause for this inter-patient variability of antiplatelet and anticoagulant drugs...
July 2017: Expert Opinion on Drug Metabolism & Toxicology
https://www.readbyqxmd.com/read/28421156/the-personalization-of-clopidogrel-antiplatelet-therapy-the-role-of-integrative-pharmacogenetics-and-pharmacometabolomics
#9
REVIEW
Arwa M Amin, Lim Sheau Chin, Dzul Azri Mohamed Noor, Muhamad Ali Sk Abdul Kader, Yuen Kah Hay, Baharudin Ibrahim
Dual antiplatelet therapy of aspirin and clopidogrel is pivotal for patients undergoing percutaneous coronary intervention. However, the variable platelets reactivity response to clopidogrel may lead to outcome failure and recurrence of cardiovascular events. Although many genetic and nongenetic factors are known, great portion of clopidogrel variable platelets reactivity remain unexplained which challenges the personalization of clopidogrel therapy. Current methods for clopidogrel personalization include CYP2C19 genotyping, pharmacokinetics, and platelets function testing...
2017: Cardiology Research and Practice
https://www.readbyqxmd.com/read/28245774/potential-usefulness-of-clopidogrel-pharmacogenetics-in-cerebral-endovascular-procedures-and-carotid-artery-stenting
#10
Jorge Duconge, Dagmar F Hernandez-Suarez
BACKGROUND: Previous reports have shown inadequate response to dual antiplatelet therapy (DAPT) with aspirin and clopidogrel in 5-30% of patients undergoing percutaneous coronary interventions (PCI), due mostly to clopidogrel resistance. This prevalence increases up to 66% in patients undergoing neurointerventional procedures. However, clinical significance of CYP2C19 genotypes in neurointerventional procedures or carotid artery stenting (CAS) is unknown. OBJECTIVE: The purpose of this review is to update our current knowledge and understanding of the pharmacogenetic basis for poor clopidogrel responsiveness in patients undergoing CAS and endovascular interventions as well as to explore usefulness of genotyping to reduce the rate of procedure-related thrombosis that results in ischemic complications...
2017: Current Clinical Pharmacology
https://www.readbyqxmd.com/read/28237404/pharmacogenetics-in-cardiovascular-diseases-state-of-the-art-and-implementation-recommendations-of-the-french-national-network-of-pharmacogenetics-rnpgx
#11
REVIEW
Fabien Lamoureux, Thomas Duflot
The use of genomic markers to predict drug response and effectiveness has the potential to improve healthcare by increasing drug efficacy and minimizing adverse effects. Polymorphisms associated with inter-individual variability in drug metabolism, transport, or pharmacodynamics of major cardiovascular drugs have been identified. These include single nucleotide polymorphisms (SNP) affecting clinical outcomes in patients receiving antiplatelet agents, oral anticoagulants and statins. Based on clinical evidence supporting genetic testing in the management of cardiovascular diseases using these drug classes, this short review presents clinical guidance regarding current pharmacogenetics implementation in routine medical practice...
April 2017: Thérapie
https://www.readbyqxmd.com/read/28064328/pharmacogenetics-of-cyp2c19-genetic-polymorphism-on-clopidogrel-response-in-patients-with-ischemic-stroke-from-saudi-arabia
#12
Adel A Alhazzani, Murali Munisamy, Gauthaman Karunakaran
OBJECTIVE: To elucidate the degree of genetic polymorphisms CYP2C19 (CYP2C19*2, CYP2C19*3) of key drug metabolizing enzymes on the antiplatelet effect of clopidogrel response in patients with acute ischemic stroke from Saudi Arabia. METHODS: A case-control study carried out at Neurology Clinics at Asser Central Hospital, Abha, Kingdom of Saudi Arabia from October 2015 to January 2016 and included 25 stroke patients responding to clopidogrel therapy and 25 stroke patients non responding to clopidogrel monotherapy...
January 2017: Neurosciences: the Official Journal of the Pan Arab Union of Neurological Sciences
https://www.readbyqxmd.com/read/27864202/implementation-of-inpatient-models-of-pharmacogenetics-programs
#13
REVIEW
Larisa H Cavallari, Craig R Lee, Julio D Duarte, Edith A Nutescu, Kristin W Weitzel, George A Stouffer, Julie A Johnson
PURPOSE: The operational elements essential for establishing an inpatient pharmacogenetic service are reviewed, and the role of the pharmacist in the provision of genotype-guided drug therapy in pharmacogenetics programs at three institutions is highlighted. SUMMARY: Pharmacists are well positioned to assume important roles in facilitating the clinical use of genetic information to optimize drug therapy given their expertise in clinical pharmacology and therapeutics...
December 1, 2016: American Journal of Health-system Pharmacy: AJHP
https://www.readbyqxmd.com/read/27767380/landscape-of-warfarin-and-clopidogrel-pharmacogenetic-variants-in-qatari-population-from-whole-exome-datasets
#14
Ambily Sivadas, Parul Sharma, Vinod Scaria
AIM: Pharmacogenetic landscapes of commonly used antiplatelet drugs, warfarin and clopidogrel have been studied in-depth in many countries. However, there is a paucity of data to understand their patterns in the Arab populations. MATERIALS & METHODS: We analyzed the whole exome sequencing datasets of 100 Qatar individuals available in public domain with this perspective. RESULTS: We characterized the allelic distribution of variants routinely tested for warfarin and clopidogrel...
October 21, 2016: Pharmacogenomics
https://www.readbyqxmd.com/read/27662521/patterns-of-antiplatelet-drug-use-after-a-first-myocardial-infarction-during-a-10-year-period
#15
Alfi Yasmina, Anthonius de Boer, Vera H M Deneer, Patrick C Souverein, Olaf H Klungel
AIMS: The aims of the present study were to assess antiplatelet drug use patterns after a first myocardial infarction (MI) and to evaluate the determinants of antiplatelet nonpersistence. METHODS: The present study was conducted in 4690 patients from the Utrecht Cardiovascular Pharmacogenetics cohort with a first MI between 1986 and 2010, who were followed for a maximum of 10 years. Medication use and event diagnosis were obtained from the Dutch PHARMO Record Linkage System...
March 2017: British Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/27249437/-the-first-results-of-the-prevalence-of-cyp2c19-genepolymorphism-in-patients-with-acute-coronary-syndrome-in-the-aktyubinsk-population
#16
G Smagulova, N Kulmurzaeva, N Seytmaganbetova, G Kurmanalina, I Talipova
To study the prevalence of polymorphic variants of CYP2C19 in residents of the Aktyubinsk region, in patients with acute coronary syndrome after percutaneous coronary intervention. We studied included 100 patients with documented acute coronary syndrome, whom stent has been implanted and double antiplatelet therapy (aspirin and clopidogrel) was administered (average age was 49.2). The control group was formed of 255 volunteers without clinical and electrocardiographic manifestations of ischemia, and cardiovascular disease (CVD)...
April 2016: Georgian Medical News
https://www.readbyqxmd.com/read/27167099/cost-effectiveness-analysis-of-personalized-antiplatelet-therapy-in-patients-with-acute-coronary-syndrome
#17
Minghuan Jiang, Joyce Hs You
AIM: This study aimed to compare the clinical and economic outcomes of pharmacogenetic-guided (PG-guided) and platelet reactivity testing-guided antiplatelet therapy for patients with acute coronary syndrome undergoing percutaneous coronary intervention. METHODS: A decision-analytic model was simulated including four antiplatelet strategies: universal clopidogrel 75 mg daily, universal alternative P2Y12 inhibitor (prasugrel or ticagrelor), PG-guided therapy, and platelet reactivity testing-guided therapy...
May 2016: Pharmacogenomics
https://www.readbyqxmd.com/read/27112273/individualized-versus-standardized-risk-assessment-in-patients-at-high-risk-for-adverse-drug-reactions-idrug-study-protocol-for-a-pragmatic-randomized-controlled-trial
#18
RANDOMIZED CONTROLLED TRIAL
Julia Carolin Stingl, Katharina Luise Kaumanns, Katrin Claus, Marie-Louise Lehmann, Kathrin Kastenmüller, Markus Bleckwenn, Gunther Hartmann, Michael Steffens, Dorothee Wirtz, Ann-Kristin Leuchs, Norbert Benda, Florian Meier, Oliver Schöffski, Stefan Holdenrieder, Christoph Coch, Klaus Weckbecker
BACKGROUND: Elderly patients are particularly vulnerable to adverse drug reactions, especially if they are affected by additional risk factors such as multimorbidity, polypharmacy, impaired renal function and intake of drugs with high risk potential. Apart from these clinical parameters, drug safety and efficacy can be influenced by pharmacogenetic factors. Evidence-based recommendations concerning drug-gene-combinations have been issued by international consortia and in drug labels. However, clinical benefit of providing information on individual patient factors in a comprehensive risk assessment aiming to reduce the occurrence and severity of adverse drug reactions is not evident...
April 26, 2016: BMC Family Practice
https://www.readbyqxmd.com/read/26979147/cardiovascular-pharmacogenomics-implications-for-patients-with-ckd
#19
REVIEW
Larisa H Cavallari, Darius L Mason
CKD is an independent risk factor for cardiovascular disease (CVD). Thus, patients with CKD often require treatment with cardiovascular drugs, such as antiplatelet, antihypertensive, anticoagulant, and lipid-lowering agents. There is significant interpatient variability in response to cardiovascular therapies, which contributes to risk for treatment failure or adverse drug effects. Pharmacogenomics offers the potential to optimize cardiovascular pharmacotherapy and improve outcomes in patients with CVD, although data in patients with concomitant CKD are limited...
March 2016: Advances in Chronic Kidney Disease
https://www.readbyqxmd.com/read/26909820/when-a-single-antiplatelet-agent-for-stroke-prevention-is-not-enough-current-evidence-and-future-applications-of-dual-antiplatelet-therapy
#20
Kristy Yuan, Anthony S Kim
For secondary stroke prevention, long-term dual antiplatelet therapy is not recommended due to increased bleeding risks. There is no specific evidence for using dual antiplatelet therapy for cervical artery dissection or for adding a second antiplatelet agent after a stroke while taking aspirin monotherapy. For patients with atrial fibrillation and stroke/TIA unable to tolerate warfarin, aspirin monotherapy is reasonable. Dual antiplatelet therapy carries a similar risk of major bleeding as warfarin that offsets reductions in stroke risk...
April 2016: Current Treatment Options in Cardiovascular Medicine
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