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The SLCO1B1 c.521T>C polymorphism is associated with dose decrease or switching during statin therapy in the

Catherine E de Keyser1, Bas J M Peters, Matthijs L Becker

  • 1Departments of aEpidemiology bInternal Medicine, Erasmus Medical Center, Rotterdam cDrug Safety Unit, The Health Care Inspectorate dDepartment of Hospital Pharmacy, Pharmacy Foundation of The Hague Hospitals - HAGA eNetherlands Consortium of Healthy Aging, The Hague fDepartment of Pharmacoepidemiology & Clinical Pharmacotherapy, Utrecht University, Utrecht gDepartment of Clinical Pharmacy, St Antonius Hospital Nieuwegein, Nieuwegein hDepartment of Hospital Pharmacy, Pharmacy Foundation of Haarlem Hospitals, Haarlem, The Netherlands iDepartment of Molecular Genetics, Pharmacogenetics and Hormone Research, Bicêtre Hospital, Paris, France.

Pharmacogenetics and Genomics
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Summary
This summary is machine-generated.

The SLCO1B1 c.521T>C polymorphism increases the risk of dose decreases or drug switches for simvastatin users. This genetic variation also impacts atorvastatin therapy, particularly at higher starting doses, indicating potential adverse drug reactions.

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Area of Science:

  • Pharmacogenetics
  • Clinical Pharmacology
  • Drug Metabolism

Background:

  • The SLCO1B1 c.521T>C polymorphism influences statin plasma concentrations.
  • This polymorphism is linked to simvastatin-induced adverse drug reactions.
  • Dose decreases or drug switches serve as indicators of adverse drug reactions.

Purpose of the Study:

  • To investigate the association between the SLCO1B1 c.521T>C polymorphism and dose adjustments or switches in simvastatin and atorvastatin therapy.
  • To identify risk factors contributing to these treatment changes.

Main Methods:

  • A population-based cohort study (Rotterdam Study) identified 1939 incident simvastatin and atorvastatin users.
  • Cox proportional hazards analysis was employed to study associations.
  • Meta-analysis was conducted using data from the Utrecht Cardiovascular Pharmacogenetics study.

Main Results:

  • Simvastatin users with the CC genotype showed a higher risk of dose decrease or switch (HR 1.74).
  • Female sex, age <70, and lower starting doses were identified as risk factors for simvastatin users.
  • Atorvastatin users with a starting dose >20 mg carrying a C allele had an increased risk (HR 3.26).
  • Meta-analysis confirmed the association for simvastatin (HR 1.69) but not for atorvastatin.

Conclusions:

  • The SLCO1B1 c.521T>C polymorphism is associated with dose decrease or switching in simvastatin users, indicating adverse drug reactions.
  • Risk factors for this association were identified in simvastatin users.
  • An association was also observed for atorvastatin users receiving higher starting doses (>20 mg).