Trial reportJournal of the American Heart Association2017
Combination Therapy Is Superior to Sequential Monotherapy for the Initial Treatment of Hypertension: A Double-Blind Randomized Controlled Trial.
Trial report in Journal of the American Heart Association, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT00994617 (Monotherapy Versus Dual Therapy for Initial Treatment for Hypertension), which is not on this map. Cited by 49 papers, 9 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.
Monotherapy Versus Dual Therapy for Initial Treatment for Hypertension
Who cites it
49 citing papers in PubMed, 9 syntheses or guidelines pooled it, 132 citations in OpenAlex.
- National Heart Center/Saudi Heart Association 2025 Guidelines for Cardiovascular Diseases Prevention and Risk Assessment.Saudi medical journal · 2026Guideline
- European guidelines for hypertension in 2024: a comparison of key recommendations for clinical practice.Nature reviews. Cardiology · 2025Guideline
- Hypertension Canada guideline for the diagnosis and treatment of hypertension in adults in primary care.Canadian family physician Medecin de famille canadien · 2025Guideline
- 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
- European stroke organisation (ESO) guideline on cerebral small vessel disease, part 2, lacunar ischaemic stroke.European stroke journal · 2024Guideline
- 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
- First-line combination therapy versus first-line monotherapy for primary hypertension.The Cochrane database of systematic reviews · 2020Pooled it
- Guide de pratique clinique en soins de première ligne d'Hypertension Canada pour le diagnostic et le traitement de l'hypertension artérielle chez les adultes.Canadian family physician Medecin de famille canadienGuideline
- Trial
- Too much, too soon? The argument against initial combination therapy in stage I hypertension.Journal of human hypertension · 2026Review
- Precision approaches to paediatric hypertension: linking pathophysiology to therapy.Pediatric nephrology (Berlin, Germany) · 2026Review
- Orthogonal Chemistry Enables Precision Nanoparticle Cofunctionalization for Tuning Immune Stimulation and Antigen Presentation.Biomacromolecules · 2026Article
- Are Angiotensin-Converting Enzyme Inhibitors Effective in the Treatment of Hypertension in Black Patients?CJC open · 2026Review
- Trends in first-line monotherapy and combination therapy for hypertension in UK primary care.British journal of clinical pharmacology · 2026Article
- Real-World Effectiveness and Safety of Ramipril/Indapamide Combination Therapy in Essential Hypertension: A Retrospective Study on UK Primary Care Records.International journal of hypertension · 2026Article
- Novel pharmacological approaches to lowering blood pressure and managing hypertension.Nature reviews. Cardiology · 2025Review
- Role of artificial intelligence in revolutionizing drug discovery.Fundamental research · 2025Review
- Chinese Guidelines for the Prevention and Treatment of Hypertension (2024 revision).Journal of geriatric cardiology : JGC · 2025Article
- Treatment optimisation for blood pressure with single-pill combinations in India (TOPSPIN) - Protocol design and baseline characteristics.International journal of cardiology. Cardiovascular risk and prevention · 2024Article
Corrections and comments
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Authors and funding
15 authors at 9 institutions in 1 country.
Funding
Abstract
backgroundGuidelines for hypertension vary in their preference for initial combination therapy or initial monotherapy, stratified by patient profile; therefore, we compared the efficacy and tolerability of these approaches. METHODS AND
resultsWe performed a 1-year, double-blind, randomized controlled trial in 605 untreated patients aged 18 to 79 years with systolic blood pressure (BP) ≥150 mm Hg or diastolic BP ≥95 mm Hg. In phase 1 (weeks 0-16), patients were randomly assigned to initial monotherapy (losartan 50-100 mg or hydrochlorothiazide 12.5-25 mg crossing over at 8 weeks), or initial combination (losartan 50-100 mg plus hydrochlorothiazide 12.5-25 mg). In phase 2 (weeks 17-32), all patients received losartan 100 mg and hydrochlorothiazide 12.5 to 25 mg. In phase 3 (weeks 33-52), amlodipine with or without doxazosin could be added to achieve target BP. Hierarchical primary outcomes were the difference from baseline in home systolic BP, averaged over phases 1 and 2 and, if significant, at 32 weeks. Secondary outcomes included adverse events, and difference in home systolic BP responses between tertiles of plasma renin. Home systolic BP after initial monotherapy fell 4.9 mm Hg (range: 3.7-6.0 mm Hg) less over 32 weeks (
conclusionsInitial combination therapy can be recommended for patients with BP >150/95 mm Hg. CLINICAL
trial registrationURL: http://www.ClinicalTrials.gov. Unique identifier: NCT00994617.
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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.