Relationship between daily dose frequency and adherence to antihypertensive pharmacotherapy: evidence from a meta-analysis

Clin Ther. 2002 Feb;24(2):302-16. doi: 10.1016/s0149-2918(02)85026-3.


Background: Rates of patient adherence (compliance) to pharmacotherapy range from <5% to >90%. Negative determinants include multiple daily dosing (MDD), chronic duration, and asymptomatic disease. Reports suggest that once-daily (QD) dosing may improve adherence, but their findings are inconclusive.

Objective: The purpose of this study was to compare the rates of adherence with QD, twice-daily (BID), and MDD antihypertensive drug regimens.

Methods: MEDLINE, Embase, and International Pharmaceutical Abstracts databases were searched to identify comparative trials of patient adherence to antihypertensive medication in solid, oral formulations. Data were combined using a random-effects meta-analytic model.

Results: Eight studies involving a total of 11,485 observations were included (1,830 for QD dosing, 4405 for BID dosing, 4147 for dosing >2 times daily [>BID], and 9655 for MDD), in which the primary objective was to assess adherence. The average adherence rate for QD dosing (91.4%, SD = 2.2%) was significantly higher (Z = 4.46, P < 0.001) than for MDD (83.2%, SD = 3.5%). This rate was also significantly higher (Z = 2.22, P = 0.026) than for BID dosing (92.7% [SD = 2.3%] vs 87.1% [SD = 2.9%]). The difference in adherence rates between BID dosing (90.8%, SD = 4.7%) and >BID dosing (86.3%, SD = 6.7%) was not significant (Z = 1.82, P = 0.069).

Conclusions: The results of this meta-analysis demonstrate that with antihypertensive medications, QD dosing regimens are associated with higher rates of adherence than either BID or MDD regimens.

Publication types

  • Meta-Analysis

MeSH terms

  • Antihypertensive Agents / administration & dosage*
  • Antihypertensive Agents / therapeutic use
  • Drug Administration Schedule
  • Humans
  • Hypertension / drug therapy
  • Patient Compliance*


  • Antihypertensive Agents