What is the clinical evidence from this study?

Study design: Systematic Review. Population: Essential hypertension (n=287083). Intervention: Single-Pill Combination (SPC) vs. Free-Combination (FC) therapy. Primary outcome: Long-term treatment adherence (Proportion of Days Covered, Medication Possession Ratio, or persistence).

What does this research mean for the field?

Single-pill combinations improve medication adherence and blood pressure control compared to free-combination therapies in hypertensive patients. Novelty: ClaimNovelty.SYNTHESIS. Consensus alignment: ConsensusAlignment.NEUTRAL.

What question did this study set out to answer?

To evaluate the effectiveness of single-pill combination therapy compared to free-combination therapy in improving long-term treatment adherence among hypertensive patients.

October 8, 2026Journal of Innovative and Creativity (Joecy)Open Access

The Effectiveness of Single-Pill Combination (SPC) Compared to Free-Combination Therapy in Improving Long-Term Treatment Adherence in Hypertensive Patients: A Systematic Review

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Key result

Single-pill combinations consistently improve long-term adherence and persistence compared to free-equivalent regimens.

n=287,083

Why the study?

Hypertension treatment adherence is suboptimal due to high pill burden in free-combination therapies, impacting blood pressure control globally.

Does Single-Pill Combination (SPC) improve treatment adherence compared to Free Combination (FC) in adult patients with essential hypertension?

Key Points

To evaluate the effectiveness of single-pill combination therapy compared to free-combination therapy in improving long-term treatment adherence among hypertensive patients.
Conducted a systematic review following PRISMA 2020 across PubMed, Semantic Scholar, and Google Scholar (2015–2025) using the PICOS framework.
Identified 9 eligible studies (3 randomized controlled trials and 6 observational cohorts; total N>270,000 adult essential hypertension patients).
Evaluated methodological quality using Cochrane RoB 2.0 for randomized trials and ROBINS-I for non-randomized cohort studies, extracting metrics including PDC, MPR, and persistence.
Eight of nine studies showed single-pill combination superiority over free combination, demonstrating higher adherence metrics (PDC and MPR) with odds ratios reaching up to 3.63.
Single-pill therapy maintained significantly better long-term treatment continuity (56.4% vs. 39.8% after 4 years in cohort data; 45.5% vs. 38.6%, p < 0.001 in administrative data).
Higher adherence with single-pill regimens was consistently linked to more effective blood pressure control across the evaluated populations.

Study Design

Type

Systematic Review (n=287,083)

Structured PICO

Does Single-Pill Combination (SPC) improve treatment adherence compared to Free Combination (FC) in adult patients with essential hypertension?

Population

Over 287,000 adult essential hypertension patients pooled from 9 studies (3 RCTs and 6 cohorts) comparing adherence to single-pill versus free-combination therapies.

Intervention

Single-Pill Combination (SPC) or Fixed-Dose Combination (FDC) antihypertensive drugs as a class

Comparator

Free Combination (FC) or Free-Equivalent Combination (FEC) containing equivalent separate antihypertensive drugs

Outcome

Adherence or long-term treatment persistence (measured by Proportion of Days Covered [PDC], Medication Possession Ratio [MPR], or discontinuation time)

Single-Pill Combination antihypertensive therapy significantly improves long-term medication adherence compared to Free-Combination regimens, thereby facilitating better blood pressure control.

Limitations

High risk of confounding bias in the majority of included observational cohort studies.
Use of open-label designs in certain RCTs, raising concerns about performance bias.
Significant heterogeneity in the methods used to measure adherence across studies (e.g., insurance claims, pill counts, electronic sensors).
Variability in healthcare system factors across different regions potentially impacting the uniform effectiveness of SPC.
Methodological heterogeneity across included studies
High risk of confounding bias in most observational cohort studies due to lack of adjustment for clinical confounders
High risk of performance bias in RCTs due to open-label designs

Implication

Supports single-pill combinations to boost adherence in hypertension; extends pill-burden associations to direct comparative evidence.

Abstract

Background: Hypertension remains a global health crisis with suboptimal blood pressure control due to poor long-term treatment adherence, exacerbated by high pill burden in free-combination therapies. Objective: This systematic review evaluates the effectiveness of Single-Pill Combination (SPC) versus Free-Combination (FC) in improving adherence among hypertensive patients. Methods: Following PRISMA 2020 guidelines, we searched PubMed, Semantic Scholar, and Google Scholar (2015-2025) for RCTs and cohort studies using PICOS framework. Nine studies (3 RCTs, 6 cohorts; N>270,000 patients) were assessed via RoB 2.0 and ROBINS-I tools, with narrative synthesis. Population/Sample: Adult essential hypertension patients receiving combination antihypertensives. Instruments/Data Analysis: Risk of bias tools and structured data extraction for adherence metrics (PDC, MPR, persistence). Results: Eight studies showed SPC superiority (higher PDC/MPR, OR up to 3.63), linked to better BP control. Conclusion: SPC should be prioritized clinically to enhance adherence and outcomes, despite methodological heterogeneity.

Discussion

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Cite This Study

Silalahi et al. (2026) conducted a systematic review in Essential hypertension (n=287,083). Single-Pill Combination (SPC) vs. Free-Combination (FC) therapy was evaluated on Long-term treatment adherence (Proportion of Days Covered, Medication Possession Ratio, or persistence). Single-Pill Combination therapy significantly improved long-term treatment adherence and persistence compared to Free-Combination therapy in eight of the nine included studies.

synapsesocial.com/papers/6ac72a1436c8cd5d094bf0cd https://doi.org/10.31004/joecy.v6i1.8966

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Implication

Supports single-pill combinations to boost adherence in hypertension; extends pill-burden associations to direct comparative evidence.

The Effectiveness of Single-Pill Combination (SPC) Compared to Free-Combination Therapy in Improving Long-Term Treatment Adherence in Hypertensive Patients: A Systematic Review

Key Points

Study Design

Structured PICO

Limitations

Implication

Abstract

Discussion

Cite This Study

The Effectiveness of Single-Pill Combination (SPC) Compared to Free-Combination Therapy in Improving Long-Term Treatment Adherence in Hypertensive Patients: A Systematic Review

Key Points

Study Design

Structured PICO

Limitations

Implication

Abstract

Discussion

Cite This Study

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