The SLCO1B1 c.521 T > C variant is not associated with muscular symptoms or PCSK9-inhibitor prescription in patients with severe hypercholesterolemia

Background The solute carrier organic anion transporter family member 1B1 (SLCO1B1) is involved in statin transport out of the blood into the liver. The SLCO1B1 c.521 T > C variant reduces its activity and has been associated with increased risk for statin associated muscle symptoms (SAMS) in particular in patients treated with simvastatin and may thereby increase the risk of statin discontinuation. Proprotein convertase subtilisin/kexin type 9-inhibitors (PCSK9i) are an alternative to statin-treatment in patients with SAMS. The aim of this study was to assess whether the SLCO1B1 c.521 T > C variant is associated with an increased rate of self-reported muscular symptoms, a decrease in statin usage and an increase in PCSK9i prescription in a cohort with severe hypercholesterolemia with indication for lipid-lowering therapy. Methods and results We included 212 patients with a mean age of 54.3 ± 12.5 years that attended our outpatient lipid clinic and were genotyped for the SLCO1B1 c.521 T > C variant. Six patients (2.8%) were homozygous and 65 patients (30.7%) were heterozygous for the c.521 T > C variant. Median LDL-cholesterol was 63 (IQR 40 – 121) mg/dL and 72 (IQR 43 – 114) mg/dL in mutation carriers and non-carriers, respectively (p=0.46). Self-reported SAMS was not different in mutation carriers and non-carriers (23.9% vs. 24.8%; p=0.89). In addition, statin usage was similar in both groups (69.0 % vs 72.3 %; p=0.63) with no differences in type of statin: rosuvastatin (51.1 % vs. 51.8 %) and atorvastatin (16.9% vs. 20.5 %; p=0.78). Prescription for PCKS9i did not differ in mutation carriers and non-carriers (52.1 % vs. 41.1 %; p=0.15). Discussion. In a cohort of patients with severe hypercholesterolemia and a high prevalence of self-reported SAMS the SLCO1B1 c.521 T > C variant was not associated with muscular symptoms during treatment with modern statins. In addition, the presence of the SLCO1B1 c.521 T > C variant was not associated with decreased prescription of statins or increased prescription of PCSK9i. These results question the clinical relevance of determining the SLCO1B1 c.521 T > C polymorphism in the era of modern statin therapy.