SynthesisBMJ (Clinical research ed.)2003
Value of low dose combination treatment with blood pressure lowering drugs: analysis of 354 randomised trials.
Synthesis in BMJ (Clinical research ed.), 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 3 registered trials, which are not on this map. Cited by 447 papers, 22 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.
Comparison of Single and Combination Diuretics in Low-Renin Hypertension
Optimum Treatment for Drug-Resistant Hypertension
Blood Pressure Lowering Effects of Amosartan Regarding Proviso in Patients With Hypertension: Prospective, Multicenter, Observational Study
Who cites it
447 citing papers in PubMed, 22 syntheses or guidelines pooled it, 1,220 citations in OpenAlex.
- "Efficacy and safety of low-dose combination (Quad pill and Triple pill) therapy versus standard of care and placebo in controlling hypertension: an updated systematic review and meta-analysis of randomized trials".Journal of human hypertension · 2026Pooled it
- Pooled it
- Rationale for the Use of Fixed Combination Therapies with Angiotensin Converting Enzyme Inhibitors and Beta-Blockers in Patients with Essential Hypertension and High Cardiovascular Risk: A Consensus Document from the Italian Society of Arterial Hypertension (Siia) and the Italian Society of Cardiovascular Prevention (SIPREC).High blood pressure & cardiovascular prevention : the official journal of the Italian Society of Hypertension · 2026Guideline
- The Japanese Society of Hypertension Guidelines for the management of elevated blood pressure and hypertension 2025 (JSH2025).Hypertension research : official journal of the Japanese Society of Hypertension · 2026Guideline
- Hypertension Canada guideline for the diagnosis and treatment of hypertension in adults in primary care.Canadian family physician Medecin de famille canadien · 2025Guideline
- Efficacy and Safety of Low-Dose Triple Single Pill Combination Versus Standard Care in the Management of Hypertension in Low- and Middle-Income Countries: A Systematic Review and Meta-analysis of Three Randomized Controlled Trials.High blood pressure & cardiovascular prevention : the official journal of the Italian Society of Hypertension · 2025Pooled it
- Guideline
- Hypertension Canada guideline for the diagnosis and treatment of hypertension in adults in primary care.CMAJ : Canadian Medical Association journal = journal de l'Association medicale canadienne · 2025Guideline
- Use of Quadruple Therapy in the Management of Hypertension: A Systematic Review of Randomized Controlled Trials.Medicina (Kaunas, Lithuania) · 2025Pooled it
- [Elevated blood pressure and hypertension : Focus of the 2024 ESC guidelines on risk reduction].Herz · 2025Guideline
- 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
- Effectiveness and Cost-Effectiveness of Team-Based Care for Hypertension: A Meta-Analysis and Simulation Study.Hypertension (Dallas, Tex. : 1979) · 2023Pooled it
- Benefits of the Polypill on Medication Adherence in the Primary and Secondary Prevention of Cardiovascular Disease: A Systematic Review.Vascular health and risk management · 2023Pooled it
- Antihypertensive drug effects on long-term blood pressure: an individual-level data meta-analysis of randomised clinical trials.Heart (British Cardiac Society) · 2022Pooled it
- How Much Lowering of Blood Pressure Is Required to Prevent Cardiovascular Disease in Patients With and Without Previous Cardiovascular Disease?Current cardiology reports · 2022Pooled it
- First-line combination therapy versus first-line monotherapy for primary hypertension.The Cochrane database of systematic reviews · 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
- Pooled it
- Blood pressure lowering efficacy of renin inhibitors for primary hypertension.The Cochrane database of systematic reviews · 2017Pooled it
- First-line combination therapy versus first-line monotherapy for primary hypertension.The Cochrane database of systematic reviews · 2017Pooled it
387 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
objectiveTo determine the average reduction in blood pressure, prevalence of adverse effects, and reduction in risk of stroke and ischaemic heart disease events produced by the five main categories of blood pressure lowering drugs according to dose, singly and in combination.
designMeta-analysis of 354 randomised double blind placebo controlled trials of thiazides, beta blockers, angiotensin converting enzyme (ACE) inhibitors, angiotensin II receptor antagonists, and calcium channel blockers in fixed dose. SUBJECTS: 40,000 treated patients and 16,000 patients given placebo.
main outcome measuresPlacebo adjusted reductions in systolic and diastolic blood pressure and prevalence of adverse effects, according to dose expressed as a multiple of the standard (recommended) doses of the drugs.
resultsAll five categories of drug produced similar reductions in blood pressure. The average reduction was 9.1 mm Hg systolic and 5.5 mm Hg diastolic at standard dose and 7.1 mm Hg systolic and 4.4 mm Hg diastolic (20% lower) at half standard dose. The drugs reduced blood pressure from all pretreatment levels, more so from higher levels; for a 10 mm Hg higher blood pressure the reduction was 1.0 mm Hg systolic and 1.1 mm Hg diastolic greater. The blood pressure lowering effects of different categories of drugs were additive. Symptoms attributable to thiazides, beta blockers, and calcium channel blockers were strongly dose related; symptoms caused by ACE inhibitors (mainly cough) were not dose related. Angiotensin II receptor antagonists caused no excess of symptoms. The prevalence of symptoms with two drugs in combination was less than additive. Adverse metabolic effects (such as changes in cholesterol or potassium) were negligible at half standard dose.
conclusionsCombination low dose drug treatment increases efficacy and reduces adverse effects. From the average blood pressure in people who have strokes (150/90 mm Hg) three drugs at half standard dose are estimated to lower blood pressure by 20 mm Hg systolic and 11 mm Hg diastolic and thereby reduce the risk of stroke by 63% and ischaemic heart disease events by 46% at age 60-69.
Indexed as
Identifiers
What OpenQuestion holds
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.