Use of Pharmacogenetic Information in the Treatment of Cardiovascular Disease

Friede, Kevin A; Li, Josephine H.; Voora, Deepak

doi:10.1373/clinchem.2016.255232

Cited by 8 publications

(6 citation statements)

References 80 publications

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“…Prasugrel has more efficient generation of active metabolite compared to clopidogrel [39, 40]. It is less dependent of CYP2C19 metabolism, and therefore not as affected by genetic variants of this enzyme [41, 42]. The most potent agent, ticagrelor, is an active drug and is not dependent on enzyme activation, i.e.…”

Section: Discussionmentioning

confidence: 99%

“…Nevertheless, it has been shown that levels of active ticagrelor are affected by genetic variants of SLCO1B1 (solute carrier organic anion transporter family member 1B1) and UGT2B7 (UDP glucuronosyltransferase family 2 member B7). These gene variants have, however, not been shown to have any clinical implication [41]. PR on ticagrelor was affected by age, BMI and smoking status i.e.…”

Section: Discussionmentioning

confidence: 99%

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A brief review on resistance to P2Y12 receptor antagonism in coronary artery disease

2019

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Background Platelet inhibition is important for patients with coronary artery disease. When dual antiplatelet therapy (DAPT) is required, a P2Y 12 -antagonist is usually recommended in addition to standard aspirin therapy. The most used P2Y 12 -antagonists are clopidogrel, prasugrel and ticagrelor. Despite DAPT, some patients experience adverse cardiovascular events, and insufficient platelet inhibition has been suggested as a possible cause. In the present review we have performed a literature search on prevalence, mechanisms and clinical implications of resistance to P2Y 12 inhibitors. Methods The PubMed database was searched for relevant papers and 11 meta-analyses were included. P2Y 12 resistance is measured by stimulating platelets with ADP ex vivo and the most used assays are vasodilator stimulated phosphoprotein (VASP), Multiplate, VerifyNow (VN) and light transmission aggregometry (LTA). Discussion/conclusion The frequency of high platelet reactivity (HPR) during clopidogrel therapy is predicted to be 30%. Genetic polymorphisms and drug-drug interactions are discussed to explain a significant part of this inter-individual variation. HPR during prasugrel and ticagrelor treatment is estimated to be 3–15% and 0–3%, respectively. This lower frequency is explained by less complicated and more efficient generation of the active metabolite compared to clopidogrel. Meta-analyses do show a positive effect of adjusting standard clopidogrel treatment based on platelet function testing. Despite this, personalized therapy is not recommended because no large-scale RCT have shown any clinical benefit. For patients on prasugrel and ticagrelor, platelet function testing is not recommended due to low occurrence of HPR.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

A brief review on resistance to P2Y12 receptor antagonism in coronary artery disease

2019

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“…The potential of genotype-driven drug dosing has for the most part yet to be realised, in part because the interaction of the genetic factors involved is sometimes complex, and in part because environmental factors may also have a significant impact on how a person responds to a drug. For example, genotype-driven prescription of warfarin, which has notoriously wide inter-individual variation in dosage requirements, largely remains in the realm of research [46].…”

Section: The Expanding Remit and Availability Of Genetic Technologymentioning

confidence: 99%

Recent developments in genetic/genomic medicine

2019

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Advances in genetic technology are having a major impact in the clinic, and mean that many perceptions of the role and scope of genetic testing are having to change. Genomic testing brings with it a greater opportunity for diagnosis, or predictions of future diagnoses, but also an increased chance of uncertain or unexpected findings, many of which may have impacts for multiple members of a person’s family. In the past, genetic testing was rarely able to provide rapid results, but the increasing speed and availability of genomic testing is changing this, meaning that genomic information is increasingly influencing decisions around patient care in the acute inpatient setting. The landscape of treatment options for genetic conditions is shifting, which has evolving implications for clinical discussions around previously untreatable disorders. Furthermore, the point of access to testing is changing with increasing provision direct to the consumer outside the formal healthcare setting. This review outlines the ways in which genetic medicine is developing in light of technological advances.

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“…13,25,[29][30][31] The other analytical performances of the DVD-array MLPA method were also estimated for point-of-care applications. 3 Assay reproducibility was expressed as the relative standard deviation of the spot intensities for triplicate assays, and was lower than 15 %. The multiplexing results confirmed the method capability for the simultaneous genotyping of up to 28 SNPs in a single DVD (8 samples per disc).…”

Section: Fig 4 Patient Analysis (A)mentioning

confidence: 99%

“…1,2 These relationships between genetic populations and drug response have been successfully applied to decision making. 3 In fact pharmacogenomics is currently considered one of the most actionable areas of the personalized medicine paradigm. 4 As a result, clinical practice guidelines based on genetic variants of specific SNPs have been defined to increase treatment efficiency and to minimize adverse reactions.…”

Section: Introductionmentioning

confidence: 99%

Digital versatile discs as platforms for multiplexed genotyping based on selective ligation and universal microarray detection

Tortajada-Genaro

Niñoles

Mena

et al. 2019

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Use of Pharmacogenetic Information in the Treatment of Cardiovascular Disease

Abstract: Many genetic variants that affect individual responses to drugs used in cardiovascular disease prevention and treatment have been described. Further study of these variants is needed before successful implementation into clinical practice.

Cited by 8 publications

References 80 publications

A brief review on resistance to P2Y12 receptor antagonism in coronary artery disease

A brief review on resistance to P2Y12 receptor antagonism in coronary artery disease

Recent developments in genetic/genomic medicine

Digital versatile discs as platforms for multiplexed genotyping based on selective ligation and universal microarray detection

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