Impact of once- or twice-daily dosing frequency on adherence to chronic cardiovascular disease medications: A meta-regression analysis

Int J Cardiol. 2016 Aug 1;216:104-9. doi: 10.1016/j.ijcard.2016.04.082. Epub 2016 May 1.


Background: Most cardiovascular diseases require patients to take one or more chronic medications, often administered multiple times daily. We sought to determine the impact of once- vs. twice-daily dosing of chronic cardiovascular disease medication on adherence.

Methods: We searched Medline and Embase from 1/1/86 to 10/15/15 for prospective studies electronically measuring adherence for at least four weeks to oral, chronic cardiovascular disease medications taken one to two times daily. Regimen adherence (the proportion of days with the appropriate number of doses taken) and timing adherence (the number of doses taken within an assigned interval divided by the total number of intervals) were outcomes of interest. Meta-regression was performed to assess how dosing frequency, adjusted for study-level covariates, impacted regimen and timing adherence.

Results: We identified 26 studies that met inclusion criteria. Forty study arms consisting of 1834 patients (range: 12-501) evaluated once-daily dosing and 18 arms consisting of 451 patients (range: 9-82) evaluated twice-daily dosing. Based upon evaluation of the regimen and timing definitions, unadjusted adherence rates were lower for twice-daily (73.8% and 50.4%) than once-daily dosing (83.1% and 74.2%) of chronic cardiovascular disease medications (p≤0.02 for both). Upon meta-regression, adjusted mean percent regimen and timing adherence for twice-daily dosing was 14.2% (95% confidence interval [CI] 6.8-21.7%) and 22.9% (95%CI 13.0-32.8%) worse than once-daily dosing (p≤0.002 for both).

Conclusion: Patients appear to be more adherent to cardiovascular disease medications dosed once-daily compared to twice-daily. Dosing frequency may be a factor for providers to consider when selecting an agent to prescribe.

Keywords: Cardiovascular disease; Electronic monitoring; Medication adherence; Meta-analysis.

Publication types

  • Comparative Study
  • Meta-Analysis

MeSH terms

  • Administration, Oral
  • Anti-Inflammatory Agents, Non-Steroidal / administration & dosage*
  • Anti-Inflammatory Agents, Non-Steroidal / therapeutic use
  • Cardiovascular Diseases / drug therapy*
  • Drug Administration Schedule
  • Female
  • Humans
  • Male
  • Medication Adherence / statistics & numerical data*
  • Prospective Studies
  • Regression Analysis
  • Treatment Outcome


  • Anti-Inflammatory Agents, Non-Steroidal