Key result
SLCO1B1 variant is not associated with statin-associated muscle symptoms in severe hypercholesterolemia.
Why the study?
The clinical relevance of the SLCO1B1 c.521 T > C variant in relation to statin-associated muscle symptoms and lipid-lowering therapy prescription in severe hypercholesterolemia patients was unclear.
Is the SLCO1B1 c.521 T>C variant associated with increased statin-associated muscle symptoms or PCSK9-inhibitor prescription in patients with severe hypercholesterolemia?
Observational (n=219)
Double-blind
Is the SLCO1B1 c.521 T>C variant associated with increased statin-associated muscle symptoms or PCSK9-inhibitor prescription in patients with severe hypercholesterolemia?
Absolute Event Rate: 25.7% vs 27.6%
p-value: p=0.76
The SLCO1B1 c.521 T>C variant is not associated with statin-associated muscle symptoms or increased PCSK9 inhibitor use in patients with severe hypercholesterolemia on contemporary therapy, suggesting routine testing may not be clinically useful.
BACKGROUND: The SLCO1B1 c.521 T > C variant, which reduces hepatic statin uptake, has been linked to an increased risk of statin-associated muscle symptoms (SAMS), particularly with simvastatin. This study aimed to assess its association with SAMS and prescription of contemporary lipid-lowering therapy in patients with severe hypercholesterolemia. METHODS AND RESULTS: We included 219 patients with a mean age of 53.9 ± 12.7 years who attended our outpatient lipid clinic and were genotyped for the SLCO1B1 c.521 T > C variant. Treating physicians and patients were unaware of genotyping results. Six patients (2.7%) were homozygous and 68 patients (31.1%) were heterozygous for the c.521 T > C variant. After treatment optimization, the median LDL cholesterol levels were 63 (IQR 40-124) mg/dL and 74 (IQR 43-129) mg/dL in mutation carriers and non-carriers, respectively (p = 0.35). Self-reported SAMS did not differ between mutation carriers and non-carriers (25.7% vs. 27.6%; p = 0.76). In addition, statin usage (70.3% vs. 73.1%; p = 0.66) and prescription rates of proprotein convertase subtilisin/kexin type-9 inhibitors (PCSK9i) (32.4% vs. 31.0%; p = 0.83) did not differ according to mutation status. DISCUSSION: In patients with severe hypercholesterolemia on contemporary statin therapy, the SLCO1B1 c.521 T > C variant was not associated with SAMS, reduced statin use, or increased prescription of PCSK9 inhibitors. The SLCO1B1 c.521 T > C variant appears to have no clear clinical relevance, but testing for it may potentially be harmful, as fear of side effects could result in statin undertreatment.
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Galli et al. (2026) conducted an observational in Severe hypercholesterolemia (n=219). SLCO1B1 c.521 T > C variant vs. Non-carriers was evaluated on Self-reported statin-associated muscle symptoms (SAMS) (p=0.76). In patients with severe hypercholesterolemia, the SLCO1B1 c.521 T > C variant was not associated with self-reported statin-associated muscle symptoms compared to non-carriers (25.7% vs 27.6%; p=0.76).
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