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Clin Ther. 2002 Feb;24(2):302-16.

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

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PharmIdeas Research & Consulting Inc, Oakville, Ontario, Canada.



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.


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


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.


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).


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.

[Indexed for MEDLINE]

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