Fixed-Dose Combination Therapy in Hypertension: A Systematic Review of Efficacy, Adherence, and Cardiovascular Outcomes

Abstract

Hypertension remains a leading contributor to global cardiovascular morbidity and mortality. Despite the
availability of effective pharmacological treatments, optimal blood pressure (BP) control continues to be suboptimal
in many populations, mainly due to poor medication adherence. Fixed-dose combination (FDC) therapies, which
incorporate two or more antihypertensive agents into a single formulation, have been proposed as a strategy to
enhance adherence and improve clinical outcomes. This systematic review aimed to assess the effectiveness,
safety, compliance, and cost-effectiveness of FDC antihypertensive therapies in comparison to monotherapy or
free-pill combinations in adults diagnosed with primary hypertension. A comprehensive search of the PubMed,
Cochrane Library, and Scopus databases was conducted for studies published between January 2020 and June
2025. Eligible studies included randomized controlled trials and observational studies that reported at least one
relevant clinical outcome, such as changes in BP, adherence levels, cardiovascular event incidence, safety profiles,
or economic impact. Twenty-eight studies met the inclusion criteria, representing a range of populations and
healthcare settings. The findings consistently indicated that FDC therapies were associated with greater reductions
in both systolic and diastolic BP, improved treatment adherence, and comparable or superior safety outcomes
relative to conventional therapeutic regimens. The methodological quality of the included studies was generally
high, with most trials assessed as having low risk of bias and observational studies rated as moderate-to-high
quality. Moreover, several studies highlighted the potential economic benefits of FDCs, including reduced pill
burden and enhanced treatment efficiency. Collectively, the evidence supports the broader adoption of FDCs as
an effective, safe, and scalable approach for the management of hypertension, particularly in resource-constrained
settings and among high-risk patient groups.