Trial reportThe American journal of cardiology2013
Effectiveness of spironolactone plus ambrisentan for treatment of pulmonary arterial hypertension (from the [ARIES] study 1 and 2 trials).
Trial report in The American journal of cardiology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers, 1 of them a synthesis 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
44 citing papers in PubMed, 1 synthesis or guideline pooled it, 106 citations in OpenAlex.
- Management of pulmonary arterial hypertension in systemic sclerosis: from classical treatments to new horizons.European respiratory review : an official journal of the European Respiratory Society · 2026Pooled it
- First-in-Man Demonstration of Direct Endothelin-Mediated Natriuresis and Diuresis.Hypertension (Dallas, Tex. : 1979) · 2017Trial
- Repurposing Heart Failure Therapies in Pulmonary Arterial Hypertension: Mechanistic Rationale, Translational Evidence, and Clinical Perspectives for SGLT2 Inhibitors and Mineralocorticoid Receptor Antagonists.Medicina (Kaunas, Lithuania) · 2026Review
- Efficacy of spironolactone in pulmonary arterial hypertension.Hypertension research : official journal of the Japanese Society of Hypertension · 2025Article
- Nephrectomy and high-salt diet inducing pulmonary hypertension and kidney damage by increasing Ang II concentration in rats.Respiratory research · 2024Article
- Management of Pulmonary Hypertension in the Context of Heart Failure with Preserved Ejection Fraction.Current hypertension reports · 2024Review
- Therapeutic targeting of mineralocorticoid receptors in pulmonary hypertension: Insights from basic research.Frontiers in cardiovascular medicine · 2023Review
- Article
- Pannexin 1: a novel regulator of acute hypoxic pulmonary vasoconstriction.Cardiovascular research · 2022Article
- Understanding the Pathobiology of Pulmonary Hypertension Due to Left Heart Disease.Circulation research · 2022Review
- Mineralocorticoid receptor activation and antagonism in cardiovascular disease: cellular and molecular mechanisms.Kidney international supplements · 2022Review
- Pulmonary Hypertension in the Context of Heart Failure With Preserved Ejection Fraction.Chest · 2021Review
- Neurohormonal modulation in pulmonary arterial hypertension.The European respiratory journal · 2021Review
- Article
- Clinical Differences and Outcomes between Methamphetamine-associated and Idiopathic Pulmonary Arterial Hypertension in the Pulmonary Hypertension Association Registry.Annals of the American Thoracic Society · 2021Article
- Novel Experimental Therapies for Treatment of Pulmonary Arterial Hypertension.Journal of experimental pharmacology · 2021Review
- Review
- Emerging therapies for right ventricular dysfunction and failure.Cardiovascular diagnosis and therapy · 2020Review
- Mineralocorticoid receptor blockade improves pulmonary hypertension and right ventricular function in bronchopulmonary dysplasia: a case report.Cardiovascular diagnosis and therapy · 2020Article
- Changes in REVEAL risk score in patients with pulmonary arterial hypertension treated with macitentan in clinical practice: results from the PRACMA study.BMC pulmonary medicine · 2020Observational
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 4 institutions in 1 country.
Funding
Abstract
In translational models of pulmonary arterial hypertension (PAH), spironolactone improves cardiopulmonary hemodynamics by attenuating the adverse effects of hyperaldosteronism on endothelin type-B receptor function in pulmonary endothelial cells. This observation suggests that coupling spironolactone with inhibition of endothelin type-A receptor-mediated pulmonary vasoconstriction may be a useful treatment strategy for patients with PAH. We examined clinical data from patients randomized to placebo or the selective endothelin type-A receptor antagonist ambrisentan (10 mg/day) and in whom spironolactone use was reported during ARIES-1 and -2, which were randomized, double-blind, placebo-controlled trials assessing the effect of ambrisentan for 12 weeks on clinical outcome in PAH. From patients randomized to placebo (n = 132) or ambrisentan (n = 67), we identified concurrent spironolactone use in 21 (15.9%) and 10 (14.9%) patients, respectively. Compared with patients treated with ambrisentan alone (n = 57), therapy with ambrisentan + spironolactone improved change in 6-minute walk distance by 94% at week 12 (mean ± SE, +38.2 ± 8.1 vs +74.2 ± 27.4 m, p = 0.11), improved plasma B-type natriuretic peptide concentration by 1.7-fold (p = 0.08), and resulted in a 90% relative increase in the number of patients improving ≥1 World Health Organization functional class (p = 0.08). Progressive illness, PAH-associated hospitalizations, or death occurred as an end point for 5.3% of ambrisentan-treated patients; however, no patient treated with ambrisentan + spironolactone reached any of these end points. In conclusion, these pilot data suggest that coupling spironolactone and endothelin type-A receptor antagonism may be clinically beneficial in PAH. Prospective clinical trials are required to further characterize our findings.
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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.