Evidence map›Paper›PMID 29655877›Full record

ArticleThe lancet. Diabetes & endocrinology2018

Endocrine and haemodynamic changes in resistant hypertension, and blood pressure responses to spironolactone or amiloride: the PATHWAY-2 mechanisms substudies.

Bryan Williams, Thomas M MacDonald, Steve V Morant, David J Webb, Peter Sever, Gordon T McInnes, Ian Ford, J Kennedy Cruickshank, Mark J Caulfield, Sandosh Padmanabhan and 4 more

Erratum issued Registry-linked trialOpen access · hybridAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in The lancet. Diabetes & endocrinology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. It is linked to trial NCT02369081 (Optimum Treatment for Drug-Resistant Hypertension), which is not on this map. Cited by 133 papers, 8 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
133citing papers in PubMed, 8 pooled it
22.4field-weighted citation impact, top 1% of its field
1 · What the graph read from 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.

2 · The registry

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.

NCT02369081 phase4unknown statusnot on this map

Optimum Treatment for Drug-Resistant Hypertension

TypeinterventionalSponsorUniversity of CambridgeRan2009 to 2015Enrolled348ConditionsHypertension, Resistant to Conventional TherapyArmsSpironolactone, Bisoprolol, Doxazosin, Placebo
3 · Its place in the literature

Who cites it

133 citing papers in PubMed, 8 syntheses or guidelines pooled it, 323 citations in OpenAlex.

  1. Guideline
  2. Guideline
  3. CMAJ : Canadian Medical Association journal = journal de l'Association medicale canadienne · 2025
    Guideline
  4. Pooled it
  5. 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 · 2025
    Guideline
  6. Guideline
  7. Guideline
  8. Guideline
  9. Trial
  10. Trial
  11. Trial
  12. Trial
  13. Trial
  14. Article
  15. Article
  16. Review
  17. Article
  18. Article
  19. Primary aldosteronism.Nature reviews. Disease primers · 2026
    Review
  20. Review

73 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

14 authors at 9 institutions in 1 country.

Bryan WilliamsUCL Institute of Cardiovascular Sciences, University College London, London, UK; National Institute for Health Research, UCL Hospitals Biomedical Research Centre, London, UK.
Thomas M MacDonaldMedicines Monitoring Unit, Molecular and Clinical Medicine, University of Dundee, Dundee, UK.
Steve V MorantMedicines Monitoring Unit, Molecular and Clinical Medicine, University of Dundee, Dundee, UK.
David J WebbClinical Pharmacology Unit, Centre for Cardiovascular Science, Queen's Medical Research Institute, University of Edinburgh, Edinburgh, UK.
Peter SeverCentre of Circulatory Health, Imperial College London, London, UK.
Gordon T McInnesBHF Glasgow Cardiovascular Research Centre, Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, UK.
Ian FordRobertson Centre for Biostatistics, University of Glasgow, Glasgow, UK.
J Kennedy CruickshankDepartment of Nutritional Sciences, King's College London, London, UK.
Mark J CaulfieldWilliam Harvey Research Institute, Queen Mary University of London, London, UK; NIHR Barts Hospital Biomedical Research Centre, London, UK.
Sandosh PadmanabhanBHF Glasgow Cardiovascular Research Centre, Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, UK.
Isla S MackenzieMedicines Monitoring Unit, Molecular and Clinical Medicine, University of Dundee, Dundee, UK.
Jackie SalsburyWilliam Harvey Research Institute, Queen Mary University of London, London, UK; NIHR Barts Hospital Biomedical Research Centre, London, UK.
Morris J BrownWilliam Harvey Research Institute, Queen Mary University of London, London, UK; NIHR Barts Hospital Biomedical Research Centre, London, UK. Electronic address: morris.brown@qmul.ac.uk.
British Hypertension Society programme of Prevention And Treatment of Hypertension With Algorithm based Therapy (PATHWAY) Study Group
William Harvey Research Institute · GBQueen Mary University of London · GBUniversity of London · GBUniversity of Dundee · GBUniversity of Glasgow · GBKing's College London · GBThe Queen's Medical Research Institute · GBImperial College London · GBNational Institute for Health Research · GB

Funding

British Heart Foundation SP/08/002Medical Research Council MC_PC_13090
6 · The paper itself

Abstract

backgroundIn the PATHWAY-2 study of resistant hypertension, spironolactone reduced blood pressure substantially more than conventional antihypertensive drugs. We did three substudies to assess the mechanisms underlying this superiority and the pathogenesis of resistant hypertension.

methodsPATHWAY-2 was a randomised, double-blind crossover trial done at 14 UK primary and secondary care sites in 314 patients with resistant hypertension. Patients were given 12 weeks of once daily treatment with each of placebo, spironolactone 25-50 mg, bisoprolol 5-10 mg, and doxazosin 4-8 mg and the change in home systolic blood pressure was assessed as the primary outcome. In our three substudies, we assessed plasma aldosterone, renin, and aldosterone-to-renin ratio (ARR) as predictors of home systolic blood pressure, and estimated prevalence of primary aldosteronism (substudy 1); assessed the effects of each drug in terms of thoracic fluid index, cardiac index, stroke index, and systemic vascular resistance at seven sites with haemodynamic monitoring facilities (substudy 2); and assessed the effect of amiloride 10-20 mg once daily on clinic systolic blood pressure during an optional 6-12 week open-label runout phase (substudy 3). The PATHWAY-2 trial is registered with EudraCT, number 2008-007149-30, and ClinicalTrials.gov, number NCT02369081.

findingsOf the 314 patients in PATHWAY-2, 269 participated in one or more of the three substudies: 126 in substudy 1, 226 in substudy 2, and 146 in substudy 3. Home systolic blood pressure reduction by spironolactone was predicted by ARR (r

interpretationOur results suggest that resistant hypertension is commonly a salt-retaining state, most likely due to inappropriate aldosterone secretion. Mineralocorticoid receptor blockade by spironolactone overcomes the salt retention and resistance of hypertension to treatment. Amiloride seems to be as effective an antihypertensive as spironolactone, offering a substitute treatment for resistant hypertension.

fundingBritish Heart Foundation and UK National Institute for Health Research.

Indexed as

AldosteroneAmilorideAntihypertensive AgentsBisoprololBlood PressureDoxazosinFemaleHemodynamicsHumansHypertensionMaleMiddle AgedRandomized Controlled Trials as TopicSpironolactoneAldosteroneAmilorideAntihypertensive AgentsBisoprololDoxazosinSpironolactone

Identifiers

PMID29655877
PMCPMC5966620
OpenAlexW2796868581

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

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.