Contemporary Pharmacotherapeutic Approach in Pulmonary Arterial Hypertension

Ahari, Jalil; Bhatnagar, Akshay; Johnson, Anna; Gomberg‐Maitland, Mardi

doi:10.1016/j.ccm.2020.10.002

Cited by 3 publications

(1 citation statement)

References 53 publications

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“…In 1995, the US Food and Drug Administration approved epoprostenol for PAH treatment, which improved patient outcomes and paved the way for a new era of targeted drug therapy for PAH treatment. [5] At present, the clinical use of targeted drugs mainly includes endothelin receptor antagonists, phosphodiesterase-5 inhibitors, soluble guanylate cyclase agonists, prostacyclin analogs, and prostacyclin receptor agonists.…”

Section: Introductionmentioning

confidence: 99%

A Network Meta-analysis of the Efficacy and Safety of Targeted Drug Combinations in the Treatment of Pulmonary Arterial Hypertension

Wang,

Wei,

Wang

et al. 2023

Cardiology Discovery

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Objective: This network meta-analysis aims to compare the efficacy and safety of different targeted drug combination treatment for pulmonary arterial hypertension (PAH). Methods: Searches were conducted in Cochrane, PubMed, EMBASE, China National Knowledge Infrastructure, China Biomedical Literature Database, Wanfang Database, and VIP Chinese Science and Technology Journal Data to identify both published and unpublished randomized controlled trials from inception until January 1, 2022. The risk of bias in the included studies was assessed in accordance with the Cochrane Handbook for Systematic Reviews of Interventions. A network meta-analysis was performed using Stata 16.0 software. The efficacy and safety of different targeted drugs combined treatment for PAH were evaluated based on forest plot, funnel plot, and surface under the cumulative ranking. Results: A total of 29 randomized controlled trails with 4,448 patients treated with 10 different types of targeted drug combinations were included in this study. The results of the surface under the cumulative ranking showed that the combination regimen was the best clinical option to improve symptoms and delay progression in patients with pulmonary artery hypertension compared with monotherapy. Sildenafil in combination with ambrisentan significantly improved the 6-minute walk distance and reduced N-terminal pro-brain natriuretic peptide levels. Bosentan in combination with sildenafil significantly reduced mean pulmonary artery pressure, whereas bosentan in combination with epoprostenol was more effective than other combinations in reducing pulmonary vascular resistance. Bosentan in combination with tadalafil significantly improved the Borg dyspnea score, and bosentan in combination with iloprost was the best combination for improving World Health Organization functional class/New York Heart Association functional class. In terms of safety, there was no significant reduction in the incidence of adverse events, hospitalizations, or all-cause mortality for combination therapy compared with monotherapy. Bosentan combined with sildenafil significantly reduced the risk of serious adverse events, but the risk of discontinuation due to an adverse event was higher than monotherapy. Sildenafil combined with epoprostenol reduced the risk of clinical worsening in patients with PAH. Conclusion: Compared with monotherapy, targeted drug combinations for PAH significantly improves exercise tolerance, pulmonary hemodynamic parameters, and reduces the risk of serious adverse events and clinical worsening in patients. Bosentan in combination with sildenafil and bosentan in combination with iloprost are combinations of targeted agents with significant efficacy and better safety profile than monotherapy for the treatment of PAH. Sildenafil in combination with epoprostenol has a low risk of clinical worsening in PAH.

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Section: Introductionmentioning

confidence: 99%

A Network Meta-analysis of the Efficacy and Safety of Targeted Drug Combinations in the Treatment of Pulmonary Arterial Hypertension

Wang,

Wei,

Wang

et al. 2023

Cardiology Discovery

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Otud6b induces pulmonary arterial hypertension by mediating the Calpain-1/HIF-1α signaling pathway

Liu,

Tang,

Wang

et al. 2024

Cell. Mol. Life Sci.

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Pulmonary hypertension (PAH) is a cardiopulmonary disease in which pulmonary artery pressure continues to rise, leading to right heart failure and death. Otud6b is a member of the ubiquitin family and is involved in cell proliferation, apoptosis and inflammation. The aim of this study was to understand the role and mechanism of Otud6b in PAH. C57BL/6 and Calpain-1 knockout (KO) mice were exposed to a PAH model induced by 10% oxygen. Human pulmonary artery endothelial cells (HPACEs) and human pulmonary artery smooth muscle cells (HPASMCs) were exposed to 3% oxygen to establish an in vitro model. Proteomics was used to determine the role of Otud6b and its relationship to Calpain-1/HIF-1α signaling. The increased expression of Otud6b is associated with the progression of PAH. ROtud6b activates Otud6b, induces HIF-1α activation, increases the production of ET-1 and VEGF, and further aggravates endothelial injury. Reducing Otud6b expression by tracheal infusion of siOtud6b has the opposite effect, improving hemodynamic and cardiac response to PAH, reducing the release of Calpain-1 and HIF-1α, and eliminating the pro-inflammatory and apoptotic effects of Otud6b. At the same time, we also found that blocking Calpain-1 reduced the effect of Otud6b on HIF-1α, and inhibiting HIF-1α reduced the expression of Calpain-1 and Otud6b. Our study shows that increased Otud6b expression during hypoxia promotes the development of PAH models through a positive feedback loop between HIF-1α and Calpain-1. Therefore, we use Otud6b as a biomarker of PAH severity, and regulating Otud6b expression may be an effective target for the treatment of PAH. Graphical Abstract

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Protocolo terapéutico de la hipertensión pulmonar sin cardiopatía izquierda

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Tenes

2022

Medicine - Programa de Formación Médica Continuada Acreditado

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Contemporary Pharmacotherapeutic Approach in Pulmonary Arterial Hypertension

Cited by 3 publications

References 53 publications

A Network Meta-analysis of the Efficacy and Safety of Targeted Drug Combinations in the Treatment of Pulmonary Arterial Hypertension

A Network Meta-analysis of the Efficacy and Safety of Targeted Drug Combinations in the Treatment of Pulmonary Arterial Hypertension

Otud6b induces pulmonary arterial hypertension by mediating the Calpain-1/HIF-1α signaling pathway

Protocolo terapéutico de la hipertensión pulmonar sin cardiopatía izquierda

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