Association Between Age and Low-Density Lipoprotein Cholesterol Response to Statins : A Danish Nationwide Cohort Study

Abstract

Background: There is large patient-to-patient variability in the low-density lipoprotein cholesterol (LDL-C) response to statin treatment. The reduction in LDL-C may depend on the age of the patient treated-particularly in older adults, who have been substantially underrepresented in randomized controlled trials.

Objective: To investigate the association between age and the LDL-C reduction by statins.

Design: Nationwide, register-based cohort study.

Setting: Denmark, 2008 to 2018.

Participants: 82 958 simvastatin or atorvastatin initiators with LDL-C measurements before and during statin use.

Measurements: Statin response, defined as percentage reduction in prestatin LDL-C level, and percentage reduction differences (PRDs) according to age and simvastatin or atorvastatin dose based on a longitudinal model for LDL-C.

Results: Among 82 958 statin initiators, 10 388 (13%) were aged 75 years or older. With low- to moderate-intensity statins, initiators aged 75 years or older had greater mean LDL-C percentage reductions than initiators younger than 50 years-for example, 39.0% versus 33.8% for simvastatin, 20 mg, and 44.2% versus 40.2% for atorvastatin, 20 mg. The adjusted PRD for initiators aged 75 years compared with initiators aged 50 years was 2.62 percentage points. This association was consistent for primary prevention (2.54 percentage points) and secondary prevention (2.32 percentage points) but smaller for initiators of high-intensity statins (atorvastatin, 40 mg: 1.36 percentage points; atorvastatin, 80 mg: -0.58 percentage point).

Limitation: Use of administrative data, observational pre-post comparison with a moderately high proportion of missing data, lack of information on body mass index, and the mainly White study population may limit generalizability.

Conclusion: Low- to moderate-intensity statins were associated with a greater reduction in LDL-C levels in older persons than younger persons and may be more appealing as initial treatment in older adults who are at increased risk for adverse events.

Primary funding source: The Independent Research Fund Denmark, Brødrene Hartmanns Fond, and Fonden til Lægevidenskabens Fremme.