Effect of dosing frequency on chronic cardiovascular disease medication adherence

Abstract

Background:

Many cardiovascular diseases (CVDs) require patients to take one or more long term medications, often administered multiple times a day. We sought to determine the effect of chronic CVD medication dosing frequency on medication adherence.

Methods:

A search of Medline and Embase from 1986 to December 2011 was performed. Included studies used a prospective design, assessed adults with chronic CVDs, evaluated scheduled oral medications administered one to four times daily, and measured adherence for ≥1 month using an electronic monitoring device. Mixed linear model meta-regression was used to determine how dosing frequency affected adherence using three definitions of increasing strictness: taking, regimen and timing adherence.

Results:

A total of 29 studies, comprising 41, 29, and 27 dosing frequency arms for the taking, regimen and timing adherence definitions were included. Crude pooled adherence estimates were highest when the lenient taking definition was assessed (range for dosing frequencies: 80.1%–93.1%), and lowest when the strictest timing definition was assessed (range: 57.1%–76.3%). Upon meta-regression, the adjusted weighted mean percentage adherence for twice and three times daily dosing regimens (no studies evaluated four times daily regimens), were 6.9% and 13.7% lower than once daily regimens for the taking, 14.0% and 27.5% lower for the regimen, and 22.9% and 30.4% lower for the timing adherence definition (p < 0.01 for all).

Limitations:

The presence of residual confounding and publication bias cannot be ruled out.

Conclusion:

Patients appear to be more adherent with once daily dosing compared with more frequently scheduled chronic CVD medication regimens. This finding is magnified when more stringent definitions of adherence are used.

Keywords::

• Cardiovascular disease
• Electronic monitoring
• Medication adherence
• Medication compliance
• Meta-analysis

Transparency

Declaration of funding

This research was supported by a grant from Janssen Scientific Affairs. The authors of this report are entirely responsible for its content.

Matthew S. Roberts^b

Diana M. Sobieraj^b

Soyon Lee^c

Tawfikul Alam^b

Rajbir Kaur^c

Declaration of financial/other relationships

C.I.C. has received grant funding to conduct research and honoraria as an advisory board member from Janssen Pharmaceuticals, Inc. M.S.R., D.M.S., S.L., T.A. and R.K. have disclosed that they have no significant relationships with or financial interests in any commercial companies related to this study or article.

CMRO peer reviewers may have received honoraria for their review work. The peer reviewers on this manuscript have disclosed any relevant financial relationships.

Acknowledgments

The authors would like to thank Drs. Karina W. Davidson, Peter Doro, and Ian Kronish for providing additional data from their studies needed to conduct this analysis.