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Treatment for Pulmonary Arterial Hypertension: Endothelin Receptor Antagonists01:18

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Endothelins (ETs) are potent vasoactive peptides critical in the human body's various physiological and pathological processes. One of the most promising therapeutic strategies for treating pulmonary arterial hypertension (PAH) involves counteracting the effects of these endothelins using a class of drugs known as endothelin receptor antagonists.
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Receptor tyrosine kinase inhibitors (TKIs) and calcium channel blockers (CCBs) are two critical categories of drugs employed in the treatment of pulmonary artery hypertension (PAH). PAH is a disease that causes high blood pressure in the pulmonary arteries, resulting in chest pain, fatigue, and shortness of breath.
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Pulmonary Hypertension: Classification and Pathogenesis01:30

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Pulmonary hypertension (PH) is a severe health condition in which the mean pulmonary arterial pressure increases to 25 mmHg or more, even when the body is at rest. This high pressure in the blood vessels that transport blood from the heart to the lungs can cause various symptoms, including shortness of breath, can lead to right heart failure, and significantly affect the overall quality of life.
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Treatment for Pulmonary Arterial Hypertension: Prostacyclin Receptor Agonists01:23

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Prostacyclin receptor agonists are a class of therapeutic agents integral to managing pulmonary arterial hypertension (PAH). These drugs operate by mimicking the action of prostaglandin I2, or PGI2, a naturally occurring compound in the body.
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Treatment for Pulmonary Arterial Hypertension: Phosphodiesterase Inhibitors01:28

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Important negative trials in pulmonary hypertension.

Sarah Cullivan1, Lucy McCourt, Sean Gaine

  • 1National Pulmonary Hypertension Unit, Mater Misericordiae University Hospital, Dublin, Ireland.

Current Opinion in Pulmonary Medicine
|July 7, 2025
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Recent pulmonary hypertension trials, including those for pulmonary arterial hypertension (PAH), have yielded negative results. Publishing all outcomes, even negative ones, is crucial for advancing future research and treatment strategies.

Keywords:
negative trialspulmonary arterial hypertensionpulmonary vascular diseases

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Area of Science:

  • Cardiovascular Medicine
  • Pulmonary Medicine
  • Pharmacology

Background:

  • Pulmonary arterial hypertension (PAH) pathobiology involves complex aberrant signaling pathways.
  • Recent research has explored various therapeutic targets for PAH.

Purpose of the Study:

  • To provide an overview of recent negative clinical trials in pulmonary hypertension, specifically focusing on PAH.
  • To highlight key learning points from these studies.

Main Methods:

  • Review of recent negative trial data in pulmonary hypertension.
  • Focus on specific drug candidates including tocilizumab, selonsertib, rodatristat ethyl, anastrazole, and imatinib (AV-101).

Main Results:

  • Several recent trials investigating novel therapies for PAH have reported negative outcomes.
  • Specific drugs reviewed include tocilizumab, selonsertib, rodatristat ethyl, anastrazole, and inhaled imatinib.

Conclusions:

  • Negative trial results offer valuable insights into PAH pathobiology and drug efficacy.
  • Publication of all trial outcomes, regardless of success, is essential for scientific progress and prioritizing future therapies.