Impact of <i><scp>SLCO</scp>1B1</i> Pharmacogenetic Testing on Patient and Healthcare Outcomes: A Systematic Review

Vassy, Jason L.; Chun, Sojeong; Advani, Sanjay; Ludin, Sophie A.; Smith, Jason G; Alligood, Elaine

doi:10.1002/cpt.1223

Cited by 20 publications

(11 citation statements)

References 80 publications

(263 reference statements)

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“…CPIC has published a clinical guideline on the management of patients who have specific SLCO1B1 genetic variants, specifically with respect to statin prescription and dosing. A recent systematic review reported that genotype testing may influence the prescribing of statins among high-risk patients, but the impact of SIM or cardiovascular events was not reported (Vassy et al, 2019). Peyser et al (2018) conducted a prospective randomized SLCO1B1 genotype-guided statin therapy trial in 159 patients who stopped taking statins because of a history of statin myalgia.…”

Section: Discussionmentioning

confidence: 99%

Pharmacogenetics of Statin-Induced Myotoxicity

et al. 2020

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Statins, a class of lipid-lowering medications, have been a keystone treatment in cardiovascular health. However, adverse effects associated with statin use impact patient adherence, leading to statin discontinuation. Statin-induced myotoxicity (SIM) is one of the most common adverse effects, prevalent across all ages, genders, and ethnicities. Although certain demographic cohorts carry a higher risk, the impaired quality of life attributed to SIM is significant. The pathogenesis of SIM remains to be fully elucidated, but it is clear that SIM is multifactorial. These factors include drug-drug interactions, renal or liver dysfunction, and genetics. Genetic-inferred risk for SIM was first reported by a landmark genome-wide association study, which reported a higher risk of SIM with a polymorphism in the SLCO1B1 gene. Since then, research associating genetic factors with SIM has expanded widely and has become one of the foci in the field of pharmacogenomics. This review provides an update on the genetic risk factors associated with SIM.

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Section: Discussionmentioning

confidence: 99%

Pharmacogenetics of Statin-Induced Myotoxicity

et al. 2020

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“…Few reports, however, report patient outcomes after the delivery of these pharmacogenetic results, with the most notable finding being a pilot trial that observed short-term improvements in LDL after SLCO1B1 testing (10 mg/dl decrease in LDL) [14]. However, there is some evidence that suggests the implication of SLCO1B1 results can change the prescribing pattern for providers (15). Based on the SLCO1B1 testing results and genotype determination, therapy is initiated as following: This personalized testing method allows patients to uncover their genetic make-up and the factors influencing it.…”

Section: Discussionmentioning

confidence: 99%

Statin Gene Testing: Revolutionary Tool to Increase Compliance and Care in Patients with Statin-Induced Myopathy

Vinson¹,

Badar²,

Gopalakrishnan³

et al. 2019

JCCCVT

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Modern day practitioners are utilizing their time and efforts increasingly to focus on preventative medicine. The correlation between coronary artery disease and hyperlipidemia is well established and this correlation has helped mold the field of preventative cardiovascular medicine. Clinically, patients treated with statins as per the guidelines have shown lower rates of morbidity and mortality over multiple large scale trials [2,4]. Statins have thus become a major first line therapy for treating patients with known hyperlipidemia and coronary artery disease; however, statin medications are often discontinued in a clinical setting with nearly 75% of patients discontinuing therapy within 2 years of initiation [5,7]. The 2009 SEARCH trial first identified an association between the pharmacogenetic test for solute carrier organic anion transporter family member 1B1 (SLCO1B1) and statin-associated symptoms, and has been replicated among numerous other studies, particularly with simvastatin [9-12]. There is some evidence that suggests the implication of SLCO1B1 results can change the prescribing pattern for providers [15]. With the use of this testing technology, clinicians are able to identify and predict possible statin-induced myopathy side effects in patients, increase compliance, and provide a more personalized treatment regimen.

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“…In a systematic review of four RCTs and 12 non-randomised studies of patients taking high dose simvastatin therapy of 80 mg/day for the 85 participants with myopathy their odds ratio for myopathy was 4.5 (95% CI 2.6-7.7) per copy of the C allele, and 16.9 (95% CI 4.7-61.1) for those with two alleles (CC) compared to the normal TT homozygotes [110]. The PharmGKB database assesses the evidence as level A (highest level evidence) that statins cause myopathy in patients with gene SLCO1B1 allele variants [111].…”

Section: Statins and Myopathymentioning

confidence: 99%

Optimising Seniors’ Metabolism of Medications and Avoiding Adverse Drug Events Using Data on How Metabolism by Their P450 Enzymes Varies with Ancestry and Drug–Drug and Drug–Drug–Gene Interactions

Thomas

2020

JPM

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Many individuals ≥65 have multiple illnesses and polypharmacy. Primary care physicians prescribe >70% of their medications and renew specialists’ prescriptions. Seventy-five percent of all medications are metabolised by P450 cytochrome enzymes. This article provides unique detailed tables how to avoid adverse drug events and optimise prescribing based on two key databases. DrugBank is a detailed database of 13,000 medications and both the P450 and other complex pathways that metabolise them. The Flockhart Tables are detailed lists of the P450 enzymes and also include all the medications which inhibit or induce metabolism by P450 cytochrome enzymes, which can result in undertreatment, overtreatment, or potentially toxic levels. Humans have used medications for a few decades and these enzymes have not been subject to evolutionary pressure. Thus, there is enormous variation in enzymatic functioning and by ancestry. Differences for ancestry groups in genetic metabolism based on a worldwide meta-analysis are discussed and this article provides advice how to prescribe for individuals of different ancestry. Prescribing advice from two key organisations, the Dutch Pharmacogenetics Working Group and the Clinical Pharmacogenetics Implementation Consortium is summarised. Currently, detailed pharmacogenomic advice is only available in some specialist clinics in major hospitals. However, this article provides detailed pharmacogenomic advice for primary care and other physicians and also physicians working in rural and remote areas worldwide. Physicians could quickly search the tables for the medications they intend to prescribe.

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Impact of SLCO1B1 Pharmacogenetic Testing on Patient and Healthcare Outcomes: A Systematic Review

Cited by 20 publications

References 80 publications

Pharmacogenetics of Statin-Induced Myotoxicity

Pharmacogenetics of Statin-Induced Myotoxicity

Statin Gene Testing: Revolutionary Tool to Increase Compliance and Care in Patients with Statin-Induced Myopathy

Optimising Seniors’ Metabolism of Medications and Avoiding Adverse Drug Events Using Data on How Metabolism by Their P450 Enzymes Varies with Ancestry and Drug–Drug and Drug–Drug–Gene Interactions

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