The Clinical Pharmacogenomics Implementation Consortium: CPIC Guideline for SLCO1B1 and Simvastatin-Induced Myopathy

TLDR

Statin therapy, especially simvastatin, has markedly reduced cholesterol levels, but the rs4149056 SNP in SLCO1B1 increases systemic exposure and the risk of muscle toxicity. The guideline examines how rs4149056 affects statin outcomes and tailors recommendations accordingly. Evidence strongly links rs4149056 to simvastatin‑induced myopathy. Published in Clinical Pharmacology & Therapeutics, 2012; 92(1):112–117 (doi:10.1038/clpt.2012.57).

Abstract

Cholesterol reduction from statin therapy has been one of the greatest public health successes in modern medicine. Simvastatin is among the most commonly used prescription medications. A non-synonymous coding single-nucleotide polymorphism (SNP), rs4149056, in SLCO1B1 markedly increases systemic exposure to simvastatin and the risk of muscle toxicity. This guideline explores the relationship between rs4149056 (c.521T>C, p.V174A) and clinical outcome for all statins. The strength of the evidence is high for myopathy with simvastatin. We limit our recommendations accordingly. Clinical Pharmacology & Therapeutics (2012); 92 1, 112–117. doi:10.1038/clpt.2012.57