Pharmacogenetics and Statin-Related Myopathy: What do we Know?

Turner, Richard M.; Radman, Ivana; Božina, Nada; Alfirevic, Ana

doi:10.2217/pgs-2020-0041

Cited by 8 publications

(11 citation statements)

References 27 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The rs4149056 (p.V174A) missense variant in the solute carrier organic anion transporter family member 1B1 ( SLCO1B1 ) reduces the intrinsic activity of its encoded hepatic influx transporter, OATP1B1. This variant has been correlated with increased statin exposure, particularly for simvastatin acid, and consistently associated with simvastatin muscle toxicity ranging from mild events to severe myopathy and rhabdomyolysis [ 26 – 29 ]. Although a strong pharmacokinetic association is recognised between atorvastatin and SLCO1B1 rs4149056, its influence on atorvastatin muscle toxicity remains less clear than for simvastatin [ 30 , 31 ].…”

Section: Pharmacogenomics In Clinical Cardiovascular Medicinementioning

confidence: 99%

The Interface of Therapeutics and Genomics in Cardiovascular Medicine

Magavern

Kaski

Turner

et al. 2021

Cardiovasc Drugs Ther

View full text Add to dashboard Cite

Pharmacogenomics has a burgeoning role in cardiovascular medicine, from warfarin dosing to antiplatelet choice, with recent developments in sequencing bringing the promise of personalised medicine ever closer to the bedside. Further scientific evidence, real-world clinical trials, and economic modelling are needed to fully realise this potential. Additionally, tools such as polygenic risk scores, and results from Mendelian randomisation analyses, are only in the early stages of clinical translation and merit further investigation. Genetically targeted rational drug design has a strong evidence base and, due to the nature of genetic data, academia, direct-to-consumer companies, healthcare systems, and industry may meet in an unprecedented manner. Data sharing navigation may prove problematic. The present manuscript addresses these issues and concludes a need for further guidance to be provided to prescribers by professional bodies to aid in the consideration of such complexities and guide translation of scientific knowledge to personalised clinical action, thereby striving to improve patient care. Additionally, technologic infrastructure equipped to handle such large complex data must be adapted to pharmacogenomics and made user friendly for prescribers and patients alike.

show abstract

Section: Pharmacogenomics In Clinical Cardiovascular Medicinementioning

confidence: 99%

The Interface of Therapeutics and Genomics in Cardiovascular Medicine

Magavern

Kaski

Turner

et al. 2021

Cardiovasc Drugs Ther

View full text Add to dashboard Cite

show abstract

“…In 2019, the amount of statins prescribed in Germany was sufficient for the daily therapy of 6.9 million patients with standard doses 10 . While generally well tolerated, this class of drugs has some side effects, of which myopathy is clinically relevant and affects treatment adherence 11 , 12 , 13 , 14 . However, myopathy is not typically present until at least 6 months after the initiation of statin treatment 15 .…”

Section: Statinsmentioning

confidence: 99%

“…Collins et al reported that, in randomised controlled trials, 11.7% of patients had myalgia during five years of statin therapy compared with 11.4% of patients in the placebo group 16 . However, myopathies are much more common in clinical practice and observational studies 12 , 13 , 17 , 18 , 19 . However, deficiencies in observational studies may suggest that the risk is estimated too high or there is even a nocebo effect 16 , 20 , 21 .…”

Section: Statinsmentioning

confidence: 99%

“…SLC01B contains information for the anion transporter OATP1B1, by which statins are transported into cells, especially into the liver. As a result of this polymorphism, a less active OATP1B1 transporter is produced, which leads to increased blood statin levels and risk for myopathy 11 , 12 , 13 , 30 .…”

Section: Statinsmentioning

confidence: 99%

“…Collins et al 16 geben an, dass in randomisierten und kontrollierten Studien 11,7% der Patienten während einer 5-jährigen Statintherapie Muskelschmerzen hatten, 11,4% unter der Placebotherapie. Im klinischen Alltag und in Anwendungsstudien wird jedoch wesentlich häufiger über Myopathien berichtet 12 , 13 , 17 , 18 , 19 . Allerdings können die Mängel von Beobachtungsstudien möglicherweise ein zu hohes Risiko suggerieren oder es liegt sogar ein Nocebo-Effekt vor 16 , 20 , 21 .…”

Section: Statineunclassified

See 2 more Smart Citations

Drug-induced Myopathies

Steinmeyer

Flechtenmacher²

2021

Z Orthop Unfall

View full text Add to dashboard Cite

Differential diagnosis of muscle pain and weakness is extensive, including neurological, vertebral, arthrogenic, vascular, traumatic, immunological, endocrine, genetic and infectious aetiologies, as well as medication or toxin-related causes. Muscles are highly sensitive to a large number of drugs, especially with high doses. Although many drug classes can cause toxic myopathy, a significant number of cases are caused by lipid-lowering drugs, long-term use of corticosteroids, and, most often, alcohol misuse. Some drug interactions, e.g. those that are metabolised via the enzyme CYP3A4, can increase the serum levels of the drugs and drug-induced toxicity. A careful history of patientʼs drug and alcohol consumption is therefore vital. Clinical symptoms depend on the drug, dosage and patientʼs sensitivity. They can vary from asymptomatic increase in serum levels of creatine kinase, mild myalgia and cramps to muscle weakness, rhabdomyolysis, kidney failure and even death. The pathogenesis is often only partially known and multifactorial. Toxic myopathy is often reversible once the drug is discontinued, alternative drug therapy is started or a different dosage regimen is chosen. Complications such as acute kidney failure must be avoided, and analgesic therapy may be indicated.

show abstract