SynthesisPloS one2016
Free versus Fixed Combination Antihypertensive Therapy for Essential Arterial Hypertension: A Systematic Review and Meta-Analysis.
Synthesis in PloS one, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers, 4 of them syntheses that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
21 citing papers in PubMed, 4 syntheses or guidelines pooled it.
- Pooled it
- The Safety and Efficacy of Quadruple Ultra-Low-Dose Combination (Quadpill) for Hypertension Treatment: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.Clinical drug investigation · 2023Pooled it
- Impact of single-pill combination therapy on adherence, blood pressure control, and clinical outcomes: a rapid evidence assessment of recent literature.Journal of hypertension · 2020Pooled it
- The Japanese Society of Hypertension Guidelines for the Management of Hypertension (JSH 2019).Hypertension research : official journal of the Japanese Society of Hypertension · 2019Guideline
- The bioequivalence of fixed-dose combination tablets of bisoprolol and ramipril and its drug-drug interaction potential.Clinical and translational science · 2022Trial
- Triple drug antihypertensive single-pill combinations included as WHO essential medicines: an overview of efficacy, safety, and cost.Journal of human hypertension · 2026Review
- Maximizing blood pressure lowering effects: a review of drug class comparisons and rationale for combination approaches.Frontiers in cardiovascular medicine · 2025Review
- 2023 Guideline for the management of hypertension in the elderly population in China.Journal of geriatric cardiology : JGC · 2024Article
- 2022 Guidelines of the Taiwan Society of Cardiology and the Taiwan Hypertension Society for the Management of Hypertension.Acta Cardiologica Sinica · 2022Article
- The Number of Pills, Rather Than the Type of Renin-Angiotensin System Inhibitor, Predicts Ambulatory Blood Pressure Control in Essential Hypertensives on Triple Therapy: A Real-Life Cross-Sectional Study.Advances in therapy · 2021Observational
- Fixed-Dose Combination Medications for Treating Hypertension: A Review of Effectiveness, Safety, and Challenges.Current hypertension reports · 2020Review
- Two-drug fixed-dose combinations of blood pressure-lowering drugs as WHO essential medicines: An overview of efficacy, safety, and cost.Journal of clinical hypertension (Greenwich, Conn.) · 2020Review
- Adherence to antihypertensive fixed-dose combination among Egyptian patients presenting with essential hypertension.The Egyptian heart journal : (EHJ) : official bulletin of the Egyptian Society of Cardiology · 2020Article
- Does the Polypill Improve Patient Adherence Compared to Its Individual Formulations? A Systematic Review.Pharmaceutics · 2020Review
- The Management of Hypertension in 2018: What Should the Targets Be?Current hypertension reports · 2019Review
- Adherence to cardiovascular medication: a review of systematic reviews.Journal of public health (Oxford, England) · 2019Review
- Prevalence and real-world assessment of central aortic blood pressure in adult patients with essential hypertension uncontrolled on single anti-hypertensive agents.Indian heart journal · 2018Observational
- The Impact of Purinergic System Enzymes on Noncommunicable, Neurological, and Degenerative Diseases.Journal of immunology research · 2018Review
- Treatment adherence among adult hypertensive patients: a cross-sectional retrospective study in primary care in Romania.Patient preference and adherence · 2018Article
- Acupuncture with reinforcing and reducing twirling manipulation inhibits hippocampal neuronal apoptosis in spontaneously hypertensive rats.Neural regeneration research · 2017Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundIn a free drug combination, each Blood pressure (BP)-lowering drug is administered as a separate pill, while in a fixed drug combination several BP-lowering agents are combined in a single pill. Using a single pill may enhance compliance and simplify treatment, which would translate into better clinical outcomes. The objective of this meta-analysis is to compare the effects of using a fixed combination versus free combination of BP-lowering agents in the management of patients with essential hypertension.
methodsWe searched Cochrane CENTRAL, MEDLINE, and EMBASE for randomized clinical trials (RCTs) addressing the objective of the review and assessing at least one of the following outcomes: BP-lowering efficacy, rapidity in achieving BP target, compliance, incidence of side effects, mortality, and morbidity. Two review authors independently selected eligible studies, abstracted data, and assessed risk of bias of included trials. The primary meta-analyses used a random-effects model.
resultsWe identified seven RCTs with a total of 397 participants. Meta-analysis of efficacy in controlling BP showed a non-significant reduction of mean systolic BP of 0.81 mmHg (95% CI -3.25, 1.64) favoring the fixed combination group. As for adverse events, results showed a non-significant 13% risk reduction favoring the free combination (risk ratio 1.13, 95% CI 0.85, 1.5). Low quality of evidence was noted for both outcomes. Rapidity in achieving BP target was assessed in only one trial, and the results favored the fixed combination. Adherence to treatment was assessed in three trials, no pooled analysis was possible for this outcome. None of the included trials assessed mortality and morbidity.
conclusionThe available low quality evidence does not confirm or rule out a substantive difference between fixed combination and free combination therapy in the management of HTN. Well designed RCTs with a long duration of follow-up and assessment of morbidity and mortality outcomes are needed.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.