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antiplatelet pharmacogenetics

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
Alfi Yasmina, Anthonius de Boer, Vera H M Deneer, Patrick C Souverein, Olaf H Klungel
AIMS: To assess antiplatelet use patterns after a first myocardial infarction (MI) and to evaluate the determinants of antiplatelet non-persistence. METHODS: This study was conducted in 4,690 patients from the Utrecht Cardiovascular Pharmacogenetics cohort with first MI between 1986-2010, who were followed for a maximum of 10 years. Medication use and event diagnosis were obtained from the Dutch PHARMO Record Linkage System. Antiplatelet users were classified as persistent users (gap between prescriptions ≤ 90 days), non-persistent users (>90 days gap and no refills), and restarters (a new prescription after a > 90 days gap)...
September 23, 2016: British Journal of Clinical Pharmacology
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
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
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...
2016: BMC Family Practice
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
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
Ku-Lang Chang, Kristin Weitzel, Siegfried Schmidt
Clinical pharmacogenetics, the use of genetic data to guide drug therapy decisions, is beginning to be used for medications commonly prescribed by family physicians. However, clinicians are largely unfamiliar with principles supporting clinical use of this type of data. For example, genetic variability in the cytochrome P450 2D6 drug metabolizing enzyme can alter the clinical effects of some opioid analgesics (e.g., codeine, tramadol), whereas variability in the CYP2C19 enzyme affects the antiplatelet agent clopidogrel...
October 1, 2015: American Family Physician
Guigao Lin, Lang Yi, Kuo Zhang, Lunan Wang, Rui Zhang, Jiehong Xie, Jinming Li
Laboratories are increasingly requested to perform CYP2C19 genetic testing when managing clopidogrel therapy, especially in patients with acute coronary syndrome undergoing percutaneous coronary intervention. To ensure high quality molecular testing and ascertain that the referring clinician has the correct information for CYP2C19 genotype-directed antiplatelet therapy, a proficiency testing scheme was set up to evaluate the laboratory performance for the entire testing process. Proficiency panels of 10 cell samples encompassing the common CYP2C19 genetic polymorphisms were distributed to 62 participating laboratories for routine molecular testing and the responses were analyzed for accuracy of genotyping and the reporting of results...
2015: PloS One
Yao Yang, Joshua P Lewis, Jean-Sébastien Hulot, Stuart A Scott
INTRODUCTION: Aspirin, clopidogrel, prasugrel and ticagrelor are antiplatelet agents for the prevention of ischemic events in patients with acute coronary syndromes (ACS), percutaneous coronary intervention (PCI) and other indications. Variability in response is observed to different degrees with these agents, which can translate to increased risks for adverse cardiovascular events. As such, potential pharmacogenetic determinants of antiplatelet pharmacokinetics, pharmacodynamics and clinical outcomes have been actively studied...
2015: Expert Opinion on Drug Metabolism & Toxicology
Nikita Malhotra, Joseph Abunassar, George A Wells, Ruth McPherson, Angel Fu, Benjamin Hibbert, Marino Labinaz, Michel Le May, Alexander Dick, Chris Glover, Michael Froeschl, Jean-François Marquis, Luan Tran, Jordan Bernick, Aun-Yeong Chong, Derek Y F So
BACKGROUND: A therapeutic window in antiplatelet treatment has been associated with concurrent lowering of bleeding and ischemic risks. Prasugrel and ticagrelor provide potent platelet inhibition, but may increase bleeding. No study has evaluated a personalized therapy with selective use of novel P2Y12 inhibitory agents compared to empiric ticagrelor use. The objective of this study was to compare a personalized anti-platelet therapy strategy to empiric ticagrelor in achieving a therapeutic window...
October 15, 2015: International Journal of Cardiology
S Ross, S Nejat, G Paré
There is considerable interindividual variation in the response to antiplatelet and anticoagulant therapies. It has been proposed that this variability in drug response may be attributable to genetic variants. Thus, pharmacogenetics may help to accurately predict response to cardiovascular disease (CVD) therapies in order to maximize drug efficacy, minimize drug toxicity, and to tailor personalized care for these patients. Although the clinical utility of pharmacogenetics is promising, its adoption in clinical practice has been slow...
June 2015: Journal of Thrombosis and Haemostasis: JTH
Renli Teng
Despite advancements in treatments for acute coronary syndromes over the last 10 years, they continue to be life-threatening disorders. Currently, the standard of treatment includes dual antiplatelet therapy consisting of aspirin plus a P2Y12 receptor antagonist. The thienopyridine class of P2Y12 receptor antagonists, clopidogrel and prasugrel, have demonstrated efficacy. However, their use is associated with several limitations, including the need for metabolic activation and irreversible P2Y12 receptor binding causing prolonged recovery of platelet function...
November 2015: Clinical Pharmacokinetics
Soon Tjin Lim, Catherine A Coughlan, Stephen J X Murphy, Israel Fernandez-Cadenas, Joan Montaner, Vincent Thijs, Lars Marquardt, Dominick J H McCabe
The majority of patients with ischaemic cerebrovascular disease (CVD) are not protected from further vascular events with antiplatelet therapy. Measurement of inhibition of platelet function ex vivo on antiplatelet therapy, using laboratory tests that correlate with the clinical effectiveness of these agents, would potentially enable physicians to tailor antiplatelet therapy to suit individuals. A systematic review of the literature was performed to collate all available data on ex vivo platelet function/reactivity in CVD patients, especially those treated with aspirin, dipyridamole or clopidogrel...
2015: Platelets
Amber L Beitelshees, Deepak Voora, Joshua P Lewis
In recent years, substantial effort has been made to better understand the influence of genetic factors on the efficacy and safety of numerous medications. These investigations suggest that the use of pharmacogenetic data to inform physician decision-making has great potential to enhance patient care by reducing on-treatment clinical events, adverse drug reactions, and health care-related costs. In fact, integration of such information into the clinical setting may be particularly applicable for antiplatelet and anticoagulation therapeutics, given the increasing body of evidence implicating genetic variation in variable drug response...
2015: Pharmacogenomics and Personalized Medicine
Suheir Nassar, Omar Amro, Hilal Abu-Rmaileh, Inji Alshaer, May Korachi, Suhail Ayesh
Clopidogrel is an antiplatelet drug used to prevent recurrent ischemic events after acute coronary syndrome and/or coronary stent implantation. Single nucleotide polymorphisms (SNPs) such as CYP2C19*2 and ABCB1 C3435T have been found to play a role in different individual responses to clopidogrel. Since the prevalence of these SNPs is generally known to differ from one population to another, the aim of this study was to examine their prevalence in both a Palestinian and Turkish population. One hundred unrelated Palestinian subjects and 100 unrelated Turkish subjects were analyzed for CYP2C19*2 and ABCB1 C3435T polymorphisms by the amplification refractory mutation system (ARMS)...
December 2014: Meta Gene
D F Mesitskaia, Iu M Nikitina, O V Lomakin, D Iu Shchekochikhin, F Iu Kopylov
AIM: To analyze the influence of clinical and pharmacogenetic factors on the risk of resistance to original or generic clopidogrel and that of cardiovascular events (CVE) during 12 months of follow-up. SUBJECTS AND METHODS: Two hundred and fifty patients admitted to Moscow hospitals in October 2011 to September 2012 were examined. All the patients received clopidogrel. During their stay at hospital, venous blood samples were collected twice (before and 7-10 days after continuous clopidogrel intake)...
2014: Terapevticheskiĭ Arkhiv
J I Cuende, C Lahoz, P Armario, J García-Alegría, J Ena, G García de Casasola, J M Mostaza
During 2013 and the first months of 2014, numerous studies have been published in the cardiovascular field. New guidelines have appeared for managing arterial hypertension and reducing cardiovascular risk by lowering cholesterol levels. New data have emerged on the considerable lipid-lowering efficacy of monoclonal antibodies against PCSK-9, in contrast, however, to the clinical trials directed towards raising HDL-cholesterol with nicotinic acid, which have not shown a reduction in the rate of cardiovascular complications...
January 2015: Revista Clínica Española
Anjana Munshi, Vandana Sharma
Stroke is the fourth leading cause of mortality and neurological disability. It is caused by an intricate interplay of environmental and genetic factors. Genes not only influence susceptibility to stroke but have also been found to alter the response to pharmacological agents and may also influence the clinical outcome of the disease. Current treatment strategies for stroke include tissue plasminogen activator, antiplatelet agents and lipid lowering drugs. These act via diverse mechanisms of actions and are centered around the management of modifiable risk factors to prevent the recurrent stroke events...
2015: Current Pharmaceutical Design
J Stitham, P Vanichakarn, L Ying, J Hwa
The use of antithrombotic agents, particularly antiplatelet drugs like aspirin and clopidogrel, has been instrumental in decreasing the risk for adverse cardiovascular events across a wide range of patients. However, despite the established benefits, the use of these medications remains suboptimal. There is a high degree of inter-individual variation in response to these treatments, whereby patients experience occlusive thromboembolic events, in spite of maintaining an appropriate treatment regimen. This has lead to the notion of antithrombotic "resistance" or "poor responders", which has been a growing concern amongst clinicians and other healthcare providers...
2014: Current Molecular Medicine
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