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Annals of Internal MedicineAssociation Between Age and Low-Density Lipoprotein Cholesterol Response to Statins

A Danish Nationwide Cohort Study

The relationship between age and the efficacy of statins in reducing low-density lipoprotein cholesterol (LDL-C) levels has been a topic of interest, especially given the underrepresentation of older adults in clinical trials. A nationwide cohort study from Denmark digs into this association, shedding light on the variability in LDL-C response to statin treatment across different age groups.

Study Design:

  • Nationwide, register-based cohort study conducted in Denmark from 2008 to 2018.
  • Participants: 82,958 individuals who began treatment with simvastatin or atorvastatin and had LDL-C measurements before and during statin use.
  • Measurements: Statin response was determined by the percentage reduction in pre-statin LDL-C levels. The study also assessed percentage reduction differences (PRDs) based on age and the specific dose of simvastatin or atorvastatin.

Key Findings:

  • Out of 82,958 statin initiators, 10,388 (13%) were aged 75 years or older.
  • Older initiators (≥75 years) on low- to moderate-intensity statins experienced a higher mean LDL-C percentage reduction compared to those below 50 years. Specifically, 39.0% vs. 33.8% for simvastatin (20 mg) and 44.2% vs. 40.2% for atorvastatin (20 mg).
  • The adjusted PRD for those aged 75 years compared to 50-year-olds was 2.62 percentage points.
  • The association was consistent for both primary (2.54 percentage points) and secondary prevention (2.32 percentage points).
  • The association was smaller for those on high-intensity statins, with a PRD of 1.36 percentage points for atorvastatin (40 mg) and -0.58 percentage point for atorvastatin (80 mg).


  • Low- to moderate-intensity statins demonstrated a more pronounced reduction in LDL-C levels in older individuals compared to younger ones, suggesting they might be a preferable initial treatment for older adults at higher risk for adverse events.

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Did You Know?
A 2019 study in the British Journal of Clinical Pharmacology found that although statins can reduce cardiovascular events in older adults, their use in those over 75 without existing cardiovascular disease remains a topic of debate due to potential side effects and limited evidence of primary prevention benefits.

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