Journal of General Internal Medicine

, Volume 34, Issue 11, pp 2559–2566 | Cite as

Statin Dosing Instructions, Medication Adherence, and Low-Density Lipoprotein Cholesterol: a Cohort Study of Incident Statin Users

  • Zachary A. MarcumEmail author
  • Hsiao-Ching Huang
  • Robert J. Romanelli
Original Research



Robust evidence is lacking on optimal timing of statin administration and its impact on patient outcomes.


This study aims to evaluate among incident statin users the relationship between those prescribed evening vs. daily dosing instructions, medication adherence, and changes in low-density lipoprotein cholesterol (LDL-c).


This is an observational cohort study at Sutter Health, a community-based healthcare system, 2010–2016.


Patients were ≥ 35 years of age as of the first statin prescription (baseline), with 12 to 36 months of electronic health record activity before and after baseline. Incident use was defined as no statin prescription in 12 months prior to baseline.

Main Measures

Differences in medication adherence (proportion of days covered ≥ 0.80) over 12 months from baseline and mean change in LDL-c between 12 and 24 months from baseline were measured using regression modeling, adjusting for baseline demographics and clinical, prescriber, and statin characteristics.

Key Results

Among 31,252 patients with valid statin prescriptions between 2010 and 2016, 5099 eligible incident statin users (mean age, 63 years) were identified, of whom 53% were prescribed evening and 47% daily dosing instructions. No difference in likelihood of statin adherence over 12 months was observed for evening vs. daily dosing (adjusted odds ratio [OR] 0.90; 95% CI 0.75, 1.08). No differences were observed in mean change in LDL-c (adjusted mean difference 1.42 mg/dL; 95% CI − 1.02, 3.89) or likelihood of attaining LDL-c < 70 mg/dL (adjusted OR 0.83; 95% CI 0.67, 1.04) for evening vs. daily dosing over a mean of 19 months follow-up.


Among incident statin users from a real-world clinical setting, those with daily and evening dosing instructions had similar adherence rates and mean changes in LDL-c. Given potential clinical equipoise for evening and daily dosing, clinicians should consider patient-tailored statin dosing instructions to reduce potentially unnecessary regimen complexity.


medication adherence pharmacoepidemiology clinical epidemiology 


Conflict of Interest

The authors declare that they do not have a conflict of interest.


ZAM was supported by an Agency for Healthcare Research & Quality grant (K12HS022982).

Compliance with Ethical Standards

The Sutter Health Institutional Review Board approved this research study.

Supplementary material

11606_2019_5180_MOESM1_ESM.docx (49 kb)
ESM 1 (DOCX 49 kb)


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Copyright information

© Society of General Internal Medicine 2019

Authors and Affiliations

  • Zachary A. Marcum
    • 1
    Email author
  • Hsiao-Ching Huang
    • 2
  • Robert J. Romanelli
    • 2
  1. 1.Department of Pharmacy, School of Pharmacy University of WashingtonSeattleUSA
  2. 2.Sutter HealthPalo Alto Medical Foundation Research InstitutePalo AltoUSA

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