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Cardiovascular pharmacogenetics

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https://www.readbyqxmd.com/read/29777510/clopidogrel-pharmacogenetics-in-iranian-patients-undergoing-percutaneous-coronary-intervention
#1
Nejat Mahdieh, Ahmad Rabbani, Ata Firouzi, Ali Zahedmehr, Maryam Hoseinimoghaddam, Sedigheh Saeidi, Hamidreza Sanati, Hosseinali Basiri, Feridoun Noohi, Bahareh Rabbani, Majid Maleki
Clopidogrel is used in patients with coronary syndromes and at risk of thrombotic events or receiving percutaneous coronary intervention (PCI) for reducing heart attack and stroke. Here we present genotype and phenotype study of Iranian patients undergoing PCI treated with clopidogrel during a 6-month period of follow-up; common variants of CYP2C19, CYP3A5, CYP3A4, and ABCB1 genes were determined as well as the patients' cardiovascular outcomes to find out the effect of these variants individually and in combination...
May 18, 2018: Cardiovascular Toxicology
https://www.readbyqxmd.com/read/29767472/the-impact-of-real-world-cardiovascular-related-pharmacogenetic-testing-in-an-insured-population
#2
Jennifer Billings, Patrick N Racsa, Kristine Bordenave, Charron L Long, Jeffrey J Ellis
BACKGROUND: Pharmacogenomics is intended to help clinicians provide the right drug to the right patient at an appropriate dose. However, limited evidence of clinical utility has slowed uptake of pharmacogenomic testing (PGT). OBJECTIVE: To evaluate the impact of real-world cardiovascular (CV)-related PGT on clinical outcomes, healthcare resource utilisation (HCRU) and cost in a large, heterogeneous population. METHODS: Individuals with Medicare Advantage Prescription Drug, Medicaid, or commercial coverage between 1/1/2011 and 9/30/2015 and ≥1 atherosclerotic CV-related diagnosis were identified...
May 16, 2018: International Journal of Clinical Practice
https://www.readbyqxmd.com/read/29700066/opportunities-and-challenges-in-cardiovascular-pharmacogenomics-from-discovery-to-implementation
#3
REVIEW
Dan M Roden, Sara L Van Driest, Quinn S Wells, Jonathan D Mosley, Joshua C Denny, Josh F Peterson
This review will provide an overview of the principles of pharmacogenomics from basic discovery to implementation, encompassing application of tools of contemporary genome science to the field (including areas of apparent divergence from disease-based genomics), a summary of lessons learned from the extensively studied drugs clopidogrel and warfarin, the current status of implementing pharmacogenetic testing in practice, the role of genomics and related tools in the drug development process, and a summary of future opportunities and challenges...
April 27, 2018: Circulation Research
https://www.readbyqxmd.com/read/29541029/pharmacogenomics-of-hypertension-and-preeclampsia-focus-on-gene-gene-interactions
#4
Marcelo R Luizon, Daniela A Pereira, Valeria C Sandrim
Hypertension is a leading cause of cardiovascular mortality, but only about half of patients on antihypertensive therapy achieve blood pressure control. Preeclampsia is defined as pregnancy-induced hypertension and proteinuria, and is associated with increased maternal and perinatal mortality and morbidity. Similarly, a large number of patients with preeclampsia are non-responsive to antihypertensive therapy. Pharmacogenomics may help to guide the personalized treatment for non-responsive hypertensive patients...
2018: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/29536347/a-literature-review-of-genetic-markers-conferring-impaired-response-to-cardiovascular-drugs
#5
REVIEW
Hitesh Shukla, Jessica Louise Mason, Abdullah Sabyah
Pharmacogenetics is an emerging area of medicine, and more work is needed to fully integrate it into a clinical setting for the benefit of patients. Genetic markers can influence the action of many drugs, including those that prevent and treat cardiovascular conditions. Genotyping is not yet commonplace, but guidelines are being put in place to help practitioners determine the effect a genetic marker may have on certain drugs. With advancements in genetic technology and falling costs, genotyping could be available to all patients via a simple saliva test...
March 13, 2018: American Journal of Cardiovascular Drugs: Drugs, Devices, and Other Interventions
https://www.readbyqxmd.com/read/29525816/adcy9-genetic-variants-and-cardiovascular-outcomes-with-evacetrapib-in-patients-with-high-risk-vascular-disease-a-nested-case-control-study
#6
Steven E Nissen, Sreekumar G Pillai, Stephen J Nicholls, Kathy Wolski, Jeffrey S Riesmeyer, Govinda J Weerakkody, Wendra M Foster, Ellen McErlean, Lin Li, Pallav Bhatnagar, Giacomo Ruotolo, A Michael Lincoff
Importance: A pharmacogenetic analysis of dalcetrapib, a cholesteryl ester transfer protein inhibitor, reported an association between a single-nucleotide polymorphism (SNP) in the ADCY9 gene (rs1967309) and reduction in major adverse cardiovascular events despite a neutral result for the overall trial. Objective: To determine whether the association between the SNP in the ADCY9 gene and a reduction in major adverse cardiovascular events could be replicated for another cholesteryl ester transfer protein inhibitor, evacetrapib, in patients with high-risk vascular disease...
March 11, 2018: JAMA Cardiology
https://www.readbyqxmd.com/read/29517519/sudden-death-in-schizophrenia
#7
Kevin J Li, Aaron P Greenstein, Lynn E Delisi
PURPOSE OF REVIEW: To examine the recent literature regarding sudden death in patients with schizophrenia and synthesize salient conclusions based on this evidence. RECENT FINDINGS: Sudden cardiac death (SCD) is the largest subset of sudden unexpected death (SUD), with up to 40% of SUD from cardiovascular causes. SCD has been associated with exposure to both first and second-generation antipsychotics. Clozapine [odds ratio (OR) 3.67, 95% confidence interval (CI) 1...
May 2018: Current Opinion in Psychiatry
https://www.readbyqxmd.com/read/29103068/antiplatelet-therapy-for-secondary-prevention-of-vascular-disease-complications
#8
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/29058944/statin-drug-interactions-and-related-adverse-reactions-an-update
#9
REVIEW
Stefano Bellosta, Alberto Corsini
Statins reduce the risk of cardiovascular morbidity and mortality in patients with or at risk for cardiovascular disease and their use is expanding, especially in elderly. Statins are prescribed on a long-term basis and may undergo drug-drug interactions (DDIs) with other drugs. Statins have different safety and tolerability, and this might affect the possibility of DDIs with other cardiovascular drugs, increasing the risk of statin-associated myopathy and hepatotoxicity. Polypharmacy and pharmacogenetic variability are potential causes of statin DDIs...
January 2018: Expert Opinion on Drug Safety
https://www.readbyqxmd.com/read/28992739/pharmacogenetic-and-pharmacogenomic-considerations-of-asthma-treatment
#10
REVIEW
Maria Gabriella Matera, Barbara Rinaldi, Luigino Calzetta, Mario Cazzola
Pharmacogenetic and pharmacogenomic approaches are already utilized in some areas, such as oncology and cardiovascular disease, for selecting appropriate patients and/or establishing treatment and dosing guidelines. This is not true in asthma although many patients have different responses to drug treatment due to genetic factors. Areas covered: Several genetic factors that affect the pharmacotherapeutic responses to asthma medications, such as β2 -AR agonists, corticosteroids, and leukotriene modifiers and could contribute to significant between-person variability in response are described...
November 2017: Expert Opinion on Drug Metabolism & Toxicology
https://www.readbyqxmd.com/read/28944433/pharmacogenetics-of-lipid-lowering-agents-an-update-review-on-genotype-dependent-effects-of-hdl-targetingand-statin-therapies
#11
REVIEW
Nathan Messas, Marie-Pierre Dubé, Jean-Claude Tardif
PURPOSE OF REVIEW: High-density lipoproteins (HDL) are involved in reverse cholesterol transport. Results from randomized trials of HDL-targeting therapies, including cholesteryl ester transfer protein (CETP) inhibitors, have shown a lack of benefit in unsegmented populations. These observations could be explained by inter-individual variability of clinical responses to such agents depending on the patients' genotypes. In parallel, although lowering of LDL cholesterol (LDL-c) with statin therapy reduces the risk of vascular events in a wide range of individuals, inter-individual variability exists with regard to LDL-c-lowering response as well as efficacy in reducing major cardiovascular events...
September 25, 2017: Current Atherosclerosis Reports
https://www.readbyqxmd.com/read/28919802/abcb1-and-abcc1-single-nucleotide-polymorphisms-in-patients-treated-with-clozapine
#12
Irina Piatkov, Dorgival Caetano, Yolinda Assur, Sue Lynn Lau, Trudi Jones, Steven C Boyages, Mark McLean
Clozapine (CZ) has superior efficacy to other antipsychotic agents in the treatment of schizophrenia and has been extensively used in clinical practice. ATP-binding cassette (ABC) transporter proteins are responsible for the distribution of various molecules as well as drugs across extracellular and intracellular membranes, including the blood-brain barrier. Genetic variations in these proteins can account for differences in treatment response. We investigated the influence of ABCB1 rs1045642 and ABCC1 rs212090 single-nucleotide polymorphisms (SNPs) on CZ serum level, clinical outcome, and changes in body mass index (BMI) in the first year of CZ treatment...
2017: Pharmacogenomics and Personalized Medicine
https://www.readbyqxmd.com/read/28892404/mechanisms-underlying-metabolic-disturbances-associated-with-psychosis-and-antipsychotic-drug-treatment
#13
Gavin P Reynolds, Olga O McGowan
The increase in cardiovascular disease and reduced life expectancy in schizophrenia likely relate to an increased prevalence of metabolic disturbances. Such metabolic risk factors in schizophrenia may result from both symptom-related effects and aetiological factors. However, a major contributory factor is that of treatment with antipsychotic drugs. These drugs differ in effects on body weight; the underlying mechanisms are not fully understood and may vary between drugs, but may include actions at receptors associated with the hypothalamic control of food intake...
August 1, 2017: Journal of Psychopharmacology
https://www.readbyqxmd.com/read/28882537/bevacizumab-induced-hypertension-clinical-presentation-and-molecular-understanding
#14
REVIEW
Megan Li, Deanna L Kroetz
Bevacizumab is a vascular endothelial growth factor-A-specific angiogenesis inhibitor indicated as an adjunct to chemotherapy for the treatment of several types of cancer. Hypertension is commonly observed during bevacizumab treatment, and high-grade toxicity can limit therapy and lead to other cardiovascular complications. The factors that contribute to interindividual variability in blood pressure response to bevacizumab treatment are not well understood. In this review, we outline research efforts to understand the mechanisms and pathophysiology of hypertension resulting from bevacizumab treatment...
February 2018: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28817866/genomic-medicine-in-primary-care
#15
Catherine Hajek
Genomic medicine is a powerful tool with great potential to improve outcomes in the primary care setting. From a broad perspective, genomic medicine can be applied to rare disease, common disease and pharmacogenetics. There are applications in which it can be used to better identify rare disease, improve screening for common disease, reduce adverse drug effects and help to identify the right medication more quickly. This article provides specific examples of clinical applications for genomic medicine in the realm of cardiovascular disease to provide a better understanding of its potential use in primary care...
2017: South Dakota Medicine: the Journal of the South Dakota State Medical Association
https://www.readbyqxmd.com/read/28753643/pharmacogenetic-meta-analysis-of-baseline-risk-factors-pharmacodynamic-efficacy-and-tolerability-endpoints-from-two-large-global-cardiovascular-outcomes-trials-for-darapladib
#16
Astrid Yeo, Li Li, Liling Warren, Jennifer Aponte, Dana Fraser, Karen King, Kelley Johansson, Allison Barnes, Colin MacPhee, Richard Davies, Stephanie Chissoe, Elizabeth Tarka, Michelle L O'Donoghue, Harvey D White, Lars Wallentin, Dawn Waterworth
Darapladib, a lipoprotein-associated phospholipase A2 (Lp-PLA2) inhibitor, failed to demonstrate efficacy for the primary endpoints in two large phase III cardiovascular outcomes trials, one in stable coronary heart disease patients (STABILITY) and one in acute coronary syndrome (SOLID-TIMI 52). No major safety signals were observed but tolerability issues of diarrhea and odor were common (up to 13%). We hypothesized that genetic variants associated with Lp-PLA2 activity may influence efficacy and tolerability and therefore performed a comprehensive pharmacogenetic analysis of both trials...
2017: PloS One
https://www.readbyqxmd.com/read/28745551/institutional-profile-of-pharmacogenetics-within-university-of-michigan-college-of-pharmacy
#17
Daniel L Hertz, Jasmine A Luzum, Amy L Pasternak, Kristen M Ward, Hao-Jie Zhu, James M Rae, Vicki L Ellingrod
The University of Michigan College of Pharmacy has made substantial investment in the area of pharmacogenomics to further bolster its activity in pharmacogenomics research, implementation and education. Four tenure-track faculty members have active research programs that focus primarily on the discovery of functional polymorphisms (HJ Zhu), and genetic associations with treatment outcomes in patients with cancer (DL Hertz), cardiovascular disease (JA Luzum) and psychiatric conditions (VL Ellingrod). Recent investments from the University and the College have accelerated the implementation of pharmacogenetics broadly across the institution and in targeted therapeutic areas...
July 26, 2017: Pharmacogenomics
https://www.readbyqxmd.com/read/28672099/impact-of-pharmacogenetics-on-efficacy-and-safety-of-statin-therapy-for-dyslipidemia
#18
REVIEW
Whitney D Maxwell, Laura B Ramsey, Samuel G Johnson, Kate G Moore, Michael Shtutman, John H Schoonover, Marina Kawaguchi-Suzuki
Interindividual variability in response to 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors, or statins, with regard to both efficacy and safety is an obvious target for pharmacogenetic research. Many genes have been identified as possible contributors to variability in statin response and safety. Genetic polymorphisms may alter the structure or expression of coded proteins, with potential impacts on lipid and statin absorption, distribution, metabolism, and elimination as well as response pathways related to the pharmacologic effect...
September 2017: Pharmacotherapy
https://www.readbyqxmd.com/read/28654154/commentary-should-pharmacogenomic-evidence-be-considered-in-clinical-decision-making-focus-on-select-cardiovascular-drugs
#19
Michael B Bottorff, David R Bright, David F Kisor
Despite advances in technology and guidelines from the Clinical Pharmacogenetics Implementation Consortium (CPIC) that focus on how to use pharmacogene test results, hurdles remain that have delayed the widespread application of pharmacogenomics in clinical practice. These hurdles include a lack of prospective randomized controlled trials to address the utility of pharmacogenomics on clinical outcomes, what the clinical algorithm for pharmacogenomics should be, and whether pharmacogenomics is cost-effective...
September 2017: Pharmacotherapy
https://www.readbyqxmd.com/read/28611364/association-of-polymorphisms-in-pharmacogenetic-candidate-genes-with-propofol-susceptibility
#20
Qi Zhong, Xiangdong Chen, Yan Zhao, Ru Liu, Shanglong Yao
Significant individual susceptibility to intravenous anesthetic propofol exists. The etiology of individual variability in the response to propofol may be influenced by genetic polymorphisms in metabolic and functional pathways. With current pharmacogenetics and modern molecular biology technologies, it is possible to study the influence of genetic polymorphisms on susceptibility to propofol. When inducing general anesthesia with intravenous propofol, high individual susceptibility to propofol was found. Using Sequenom MassARRAY single-nucleotide polymorphism (SNP) genotyping, we identified a mutation (rs6313) in the 5HT2A gene that was correlated to individual susceptibility to propofol effect-site concentration (Cep) and onset time of propofol induction...
June 13, 2017: Scientific Reports
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