Impact of Once-Daily Versus Twice-Daily Dosing Frequency on Adherence to Chronic Medications among Patients with Venous Thromboembolism
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.