Results: Patient with known SLCO1B1 genotype requiring statin therapy

A 45-year-old man is found by his GP to have high cholesterol. A decision is made to begin statin therapy. The patient has previously undergone pharmacogenomic testing as part of a clinical trial, and the results show that he has poor SLCO1B1 function. This means that he has an increased likelihood of experiencing statin-associated musculoskeletal symptoms if prescribed certain agents.

• Statins are known to cause a wide range of muscle-related adverse effects, including myalgia, myopathy and statin-induced rhabdomyolysis. Certain individuals have a predisposition to these adverse drug reactions due to variants in the genes that are involved in statin metabolism.
• Statin metabolism is mediated by several enzymes, including SLCO1B1, ABCG2 and CYP2C9. Individuals who have reduced activity of these enzymes due to genetic variation will have altered systemic exposure to statins, which can increase the risk of statin-associated musculoskeletal systems.
• If available, pharmacogenetic data can be used to inform the selection of statin therapy, reducing the risk of myopathy.
• The highest levels of evidence in this area are in relation to genetic variation in SLCO1B1, which is associated with an increased myopathy risk with all statins. Individuals with two SLCO1B1 loss-of-function alleles are described as having SLCO1B1-poor function. Individuals with one SLCO1B1 loss-of-function allele are described as having SLCO1B1-decreased function.

• At the time of writing, there is no standardised NHS guidance on altering prescriptions according to SLCO1B1 genotype. However, both the Clinical Pharmacogenetic Implementation Consortium (CPIC) and the Dutch Pharmacogenetics Working Group (DPWG) have produced pharmacogenetic prescribing recommendations for statin therapy (see the resources list below).
• Neither guideline is for or against pharmacogenomic testing in statin therapy. Instead, both provide dosing recommendations that include how to use pharmacogenetic information if it is already known.
• Pharmacogenetic dosing guidance for statins is complex and considers three variables: the statin of choice, the dose and the genetic results. You should review the latest CPIC and/or DPWG guidelines prior to adjusting any prescription.
• Individuals with SLCO1B1-poor function have a high risk of statin-induced myopathy with several agents. The risk is highest with simvastatin, which is associated with myopathy even at low doses. The risk is lower with atorvastatin and rosuvastatin, though they remain associated with myopathy when prescribed at high doses.
• There are many other factors that influence the risk of statin-associated musculoskeletal systems, including statin dose, age, drug interactions and comorbidities. As with all pharmacogenomic results, dosing should take into account these other clinical factors.
• Please refer to the CPIC website and use the latest, most up-to-date version of the relevant guideline.
• Ensure that the rationale for using a SLCO1B1-guided prescription is clearly stated in the medical notes and on the prescription, and is explained to the patient.
• Consider also adding the information about the genotype to the patient’s medical summary, to help ensure that it will be passed on to other prescribers (for example, in secondary care).

For clinicians

• Electronic Medicines Compendium
• PharmGKB: Annotation of CPIC guideline for fluvastatin and CYP2C9, SLCO1B1
• PharmGKB: Annotation of CPIC guideline for simvastatin and SLCO1B1

References:

• Cooper-DeHoff R, Niemi M, Ramsey LB and others. ‘The Clinical Pharmacogenetics Implementation Consortium Guideline for SLCO1B1, ABCG2, and CYP2C9 genotypes and statin-associated musculoskeletal symptoms’. Clinical Pharmacology & Therapeutics 2022: volume 111, issue 5, pages 1,007–1,021. DOI: 10.1002/cpt.2557