Clinical research study
Fixed-Dose Combinations Improve Medication Compliance: A Meta-Analysis

This work was presented in part at the 21st Annual Scientific Session of the American Society of Hypertension, New York, NY.
https://doi.org/10.1016/j.amjmed.2006.08.033Get rights and content

Abstract

Background

Compliance with treatment is a sine qua non for successful treatment of chronic conditions like hypertension. Fixed-dose combinations are designed to simplify the medication regimen and potentially improve compliance. However the data on comparison of fixed-dose combination with free-drug regimen to improve patient’s medication compliance is limited.

Methods

We conducted a MEDLINE search of studies using the words fixed-dose combinations, compliance and/or adherence. The inclusion criteria were studies which involved fixed-dose combination versus free-drug components of the regimen given separately. Only studies which reported patient’s compliance were included.

Results

Of the 68 studies on fixed-dose combinations, only 9 studies fulfilled the inclusion criteria. Two studies were in patients with tuberculosis, 4 in the hypertensive population, 1 in patients with human immunodeficiency virus (HIV) disease and 2 in the diabetic population. A total of 11,925 patients on fixed-dose combination were compared against 8317 patients on free-drug component regimen. Fixed-dose combination resulted in a 26% decrease in the risk of non-compliance compared with free-drug component regimen (pooled relative risk [RR] 0.74; 95% confidence interval [CI], 0.69-0.80; P <.0001). There was no evidence of heterogeneity in this analysis (χ2 = 14.49, df = 8; P = .07). A subgroup analysis of the 4 studies on hypertension showed that fixed-dose combination (pooled RR 0.76; 95% CI, 0.71-0.81; P <.0001) decreased the risk of medication non-compliance by 24% compared with free-drug combination regimen.

Conclusions

Fixed-dose combination decreases the risk of medication non-compliance and should be considered in patients with chronic conditions like hypertension for improving medication compliance which can translate into better clinical outcomes.

Section snippets

Selection of Studies

We conducted a MEDLINE search of studies using the terms: fixed-dose combinations, compliance, adherence, or persistence. We limited our search to studies in human subjects and English language in peer-reviewed journals from 1966 to November 2005. We checked the reference lists of reviewed articles and original studies identified by the electronic search to find other potentially eligible studies.

We then looked for studies in which fixed-dose combination medications were compared against the

Characteristics of Trials

The characteristic of the studies evaluated are elaborated in Table 1. Among the 9 studies on chronic disease evaluated, 2 were in the cohort of patients with tuberculosis, 1 study in patients with HIV, 4 studies in the hypertensive cohort, and 2 studies in the diabetic cohort. The study by Dezii et al 22 involved 2 subgroups, one using a fixed-dose combination of lisinopril and hydrochlorothiazide, and the other using a fixed-dose combination of enalapril and hydrochlorothiazide. The study by

Discussion

This study evaluated the role of fixed-dose combination regimens to improve medication compliance in patients with chronic illness. The results of this study show that fixed-dose combination regimens reduce the risk of non-compliance by 24%-26% compared to free-drug combination regimens. In the subgroup of patients with hypertension, fixed-dose combination regimens reduced the risk of medication non-compliance by 24% compared to free-drug combination regimens.

Conclusions

Fixed-dose combinations provide us with a strong armamentarium in chronic disease management. Non-compliance to medication regimens is reduced by 24%-26% with fixed-dose combination regimens. Fixed-dose combinations should be considered in patients with chronic conditions, like hypertension, for improving medication compliance, which can translate into better clinical outcomes.

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