Effectiveness of fixed-dose combination therapy in hypertension: systematic review and meta-analysis

Abstract

Introduction: Clinical studies have revealed that fixed-dose combinations (FDCs) of drugs can have a better effect on blood pressure than free-equivalent combinations (FECs). Our objectives were to perform an up-to-date assessment of the effectiveness of FDCs and FECs in antihypertensive therapy, to provide more accurate results by using a stratified meta-analysis.

Material and methods: A systematic review was performed in PubMed, Web of Science, and Cochrane databases according to PRISMA guidelines. The outcomes were adherence (compliance), persistence to medication, reduction of blood pressure and the safety profile. We used the Newcastle Ottawa scale or the Delphi list for the assessment of the quality of cohort studies or clinical trials, respectively. Heterogeneity was assessed using the Cochrane Q test and I² statistic.

Results: Of 301 abstracts screened, 26 primary studies and 2 other meta-analyses were identified, of which 12 studies were included in the meta-analyses and 3 studies were included in the narrative review. The FDC treatment is associated with a significant improvement in adherence and persistence in comparison with FEC treatment, e.g., the average medicine possession ratio increased with FDC by 13.1% (p < 0.001). For endpoints correlated with higher adherence (e.g., a reduction in blood pressure), a nonsignificant benefit was observed for FDCs. Moreover, it was demonstrated that higher adherence can lead to a lower risk of cardiovascular events.

Conclusions: In comparison with FECs, the FDC treatment is associated with a significant improvement in the cooperation between a doctor and a patient and with increased patients' adherence to the treatment schedule.

Keywords: fixed-dose combinations; free-equivalent combinations; hypertension.

Figure 1

PRISMA flow diagram for selection of studies identified in the systematic review

Figure 2

Meta-analysis of odds ratio for adherence to treatment. Events represent the number of patients meeting the definition of adherence (MPR or PDC ≥ 0.8). Odds ratio (OR) presented for FDC in comparison with FEC, with 95% confidence intervals (CI)

Figure 3

Meta-analysis of weighted mean difference in MPR or PDC. Mean difference presented for FDC in comparison with FEC, with 95% confidence intervals (CI). Studies not reporting variance for outcomes marked by cross estimates NA – not available.

Figure 4

Meta-analysis of persistence. Events represent the number of patients meeting the definition of persistence. Odds ratio (OR) presented for FDC in comparison with FEC, with 95% confidence intervals (CI)