Statin treatment effectiveness and the SLCO1B1*5 reduced function genotype: long-term outcomes in women and men
Authors: Türkmen Deniz , Masoli Jane A.H. , Kuo Chia-Ling , Bowden Jack , Melzer David , Pilling Luke C. 
Published: October 2021

Objective

To estimate the effect of the SLCO1B1*5 genotype (decreases statin transport) on cholesterol control and treatment duration in male and female primary care patients prescribed common statin medications.

Methods and Analysis

69,185 European-ancestry UK Biobank cohort participants prescribed simvastatin or atorvastatin (aged 40 to 79 years at first prescription; treatment duration 1 month to 29 years, mean 5.7 years). Principal outcomes were clinically high total cholesterol (>5mmol/L) at baseline, plus treatment discontinuation.

Results

48.4% of 591 females homozygous for SLCO1B1*5 decreased function genotype had raised cholesterol, vs. 41.7% of those with functioning SLCO1B1 (Odds Ratio 1.31: 95% Confidence Intervals 1.1 to 1.55, p=0.001). Fewer males had high cholesterol, and the genotype effect was attenuated. In primary care prescribing, females homozygous for SLCO1B1*5 were more likely to stop receiving these statins (29.5%) than women with normal SLCO1B1 (25.7%) (Hazard Ratio 1.19: 95%CI 1.03 to 1.37, p=0.01), amounting to five discontinuations per 100 statin-years in the SLCO1B1*5 group vs four in the normal SLCO1B1 function group. This remained significant after the first year of treatment (HR for discontinuing >1 year after first prescription 1.3: 95%CI 1.08 to 1.56; p=0.006). In men SLCO1B1*5 was only associated with treatment discontinuation in the first year.

Conclusions

In this large community sample of patients on commonly prescribed statins, the SLCO1B1*5 decreased function variant had much larger effects on cholesterol control and treatment duration in women than in men. Efforts to improve effectiveness of statin therapy in women may need to include SLCO1B1*5 genotype-guided statin selection.

What is already known about this subject

Genetic variants affecting SLCO1B1 (statin transporter) gene function increase concentrations of unmetabolized statin molecules (mostly simvastatin and atorvastatin). Previous studies of statin-treated patients have reported reduced likelihood of achieving target cholesterol levels plus increased adverse effects and medication non-adherence mainly in the first year of treatment.

However, little data have been available on key outcomes over longer follow-ups or on outcomes by sex, despite large differences in statin treatment patterns between men and women.

What this study adds

In 69,185 UK Biobank participants reporting simvastatin or atorvastatin use at baseline assessment, substantially more women had clinically high total cholesterol (>5 mmol/L) compared to men (42% vs. 25%). Female carriers of the SLCO1B1*5 (decreased SLCO1B1 function) genetic variant were especially likely to have high cholesterol, despite being on statin treatment.

In primary care records of atorvastatin and simvastatin prescribing (>10 years follow-up), female carriers of SLCO1B1*5 were more likely to stop statins. In men, SLCO1B1*5 was only associated with discontinuing statin treatment in the first year after starting treatment.