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

Objective: 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).

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

Participants: 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.

Conclusions: 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.