SynthesisJournal of the American Heart Association2016
Clinical Adverse Effects of Endothelin Receptor Antagonists: Insights From the Meta-Analysis of 4894 Patients From 24 Randomized Double-Blind Placebo-Controlled Clinical Trials.
Synthesis in Journal of the American Heart Association, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 69 papers, 5 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
69 citing papers in PubMed, 5 syntheses or guidelines pooled it, 127 citations in OpenAlex.
- Efficacy and Safety of Aprocitentan in the Treatment of Hypertension: A Meta-Analysis of Evidence from Randomized Controlled Trials.Reviews in cardiovascular medicine · 2025Pooled it
- Efficacy and safety of endothelin receptor antagonists, phosphodiesterase type 5 Inhibitors, and prostaglandins in pediatric pulmonary arterial hypertension: A network meta-analysis.Frontiers in cardiovascular medicine · 2022Pooled it
- The efficacy and safety of rivaroxaban in coronary artery disease patients with heart failure and sinus rhythm: a systematic review and meta-analysis.European journal of clinical pharmacology · 2021Pooled it
- Evidence synthesis in pulmonary arterial hypertension: a systematic review and critical appraisal.BMC pulmonary medicine · 2020Pooled it
- Incidence and risk of respiratory tract infection associated with specific drug therapy in pulmonary arterial hypertension: a systematic review.Scientific reports · 2017Pooled it
- Long-Term Treatment with Single-Tablet Combination of Macitentan and Tadalafil in Pulmonary Arterial Hypertension: Results from A DUE and Its Open-Label Period.Advances in therapy · 2026Trial
- Aprocitentan in Patients With Chronic Kidney Disease and Resistant Hypertension.Hypertension (Dallas, Tex. : 1979) · 2026Trial
- Effects of the Dual Endothelin Receptor Antagonist Aprocitentan on Body Weight and Fluid Homeostasis in Healthy Subjects on a High Sodium Diet.Clinical pharmacology and therapeutics · 2021Trial
- Secondary Pharmacology Targets for Pediatric Developmental Safety Assessment of New Drugs: Clinical Pharmacology Considerations.Clinical pharmacology and therapeutics · 2026Review
- Endothelin Receptor Antagonists in Resistant Hypertension and Proteinuric Kidney Disease: Receptor Strategy and Volume Management.Journal of clinical hypertension (Greenwich, Conn.) · 2026Review
- Effect of Once-Daily Macitentan 75 mg on the Pharmacokinetics of Sildenafil, Riociguat, or Rosuvastatin in Healthy Male Participants.Journal of clinical pharmacology · 2026Article
- Review
- Article
- Novel pharmacological approaches to lowering blood pressure and managing hypertension.Nature reviews. Cardiology · 2025Review
- State of the Art in Pulmonary Arterial Hypertension: Molecular Basis, Imaging Modalities, and Right Heart Failure Treatment.Biomedicines · 2025Review
- Advances and challenges in kidney fibrosis therapeutics.Nature reviews. Nephrology · 2025Review
- ACVRL1 variation-induced hereditary hemorrhagic telangiectasia presenting with pulmonary arterial hypertension: clinical and genetic analyses of three case studies.BMC cardiovascular disorders · 2025Article
- The Selective Endothelin Receptor Antagonist SC0062 in IgA Nephropathy: A Randomized Double-Blind Placebo-Controlled Clinical Trial.Journal of the American Society of Nephrology : JASN · 2025Article
- Advanced treatment strategies for high-altitude pulmonary hypertension employing natural medicines: A review.Journal of pharmaceutical analysis · 2025Review
- Endothelin receptor antagonists in chronic kidney disease.Nature reviews. Nephrology · 2025Review
9 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 6 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundEvidence of the clinical safety of endothelin receptor antagonists (ERAs) is limited and derived mainly from individual trials; therefore, we conducted a meta-analysis. METHODS AND
resultsAfter systematic searches of the Medline, Embase, and Cochrane Library databases and the ClinicalTrials.gov website, randomized controlled trials with patients receiving ERAs (bosentan, macitentan, or ambrisentan) in at least 1 treatment group were included. All reported adverse events of ERAs were evaluated. Summary relative risks and 95% CIs were calculated using random- or fixed-effects models according to between-study heterogeneity. In total, 24 randomized trials including 4894 patients met the inclusion criteria. Meta-analysis showed that the incidence of abnormal liver function (7.91% versus 2.84%; risk ratio [RR] 2.38, 95% CI 1.36-4.18), peripheral edema (14.36% versus 9.68%; RR 1.44, 95% CI 1.20-1.74), and anemia (6.23% versus 2.44%; RR 2.69, 95% CI 1.78-4.07) was significantly higher in the ERA group compared with placebo. In comparisons of individual ERAs with placebo, bosentan (RR 3.78, 95% CI 2.42-5.91) but not macitentan (RR 1.17, 95% CI 0.42-3.31) significantly increased the risk of abnormal liver function, whereas ambrisentan (RR 0.06, 95% CI 0.01-0.45) significantly decreased that risk. Bosentan (RR 1.47, 95% CI 1.06-2.03) and ambrisentan (RR 2.02, 95% CI 1.40-2.91) but not macitentan (RR 1.08, 95% CI 0.81-1.46) significantly increased the risk of peripheral edema. Bosentan (RR 3.09, 95% CI 1.52-6.30) and macitentan (RR 2.63, 95% CI 1.54-4.47) but not ambrisentan (RR 1.30, 95% CI 0.20-8.48) significantly increased the risk of anemia. ERAs were not found to increase other reported adverse events compared with placebo.
conclusionsThe present meta-analysis showed that the main adverse effects of treatment with ERAs were hepatic transaminitis (bosentan), peripheral edema (bosentan and ambrisentan), and anemia (bosentan and macitentan).
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What Socratic 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 Socratic graph.