ArticleNigerian medical journal : journal of the Nigeria Medical Association
Targeting Novel Pathways in Pulmonary Arterial Hypertension: A Systematic Review and Meta-Analysis of New Therapeutic Agents.
Article in Nigerian medical journal : journal of the Nigeria Medical Association. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Background: Pulmonary arterial hypertension (PAH) is a progressive condition marked by vascular remodelling, increased pulmonary vascular resistance, and right ventricular dysfunction. Current vasodilator therapies fail to reverse disease progression. Alternative molecular pathways may offer improved therapeutic outcomes and potentially modify the disease course. This systematic review and meta-analysis evaluated the efficacy and safety of emerging PAH therapies targeting alternative pathways, including bone morphogenetic protein signalling, rho-kinase inhibition, estrogen modulation, AMP-activated protein kinase activation, phosphodiesterase-5 inhibition, soluble guanylate cyclase stimulation, and regenerative stem cell therapy. Methodology: A systematic review was performed following PRISMA guidelines. Randomised controlled trials (RCTs) and phase I-III studies assessing novel therapies were included. Primary outcomes were six-minute walk distance (6MWD) and haemodynamic parameters. Secondary endpoints included brain natriuretic peptide (BNP)/N-terminal pro-BNP (NT-proBNP), World Health Organization Functional Class (WHO-FC), tricuspid annular plane systolic excursion (TAPSE), and safety profile. Meta-analysis employed a random-effects model. Results: Thirteen trials (1,782 participants) met inclusion criteria. Sotatercept improved 6MWD, pulmonary vascular resistance (PVR), and NT-proBNP. Riociguat enhanced haemodynamics and WHO-FC. Metformin plus bosentan improved exercise capacity and right ventricular function. Udenafil and fasudil showed modest benefits, while anastrozole had mixed results with possible sex-specific effects. Cardiosphere-derived stem cells showed early promise for right ventricular recovery. Heterogeneity was high across studies. Conclusion: Novel therapies targeting non-vasodilatory pathways show promise in PAH, though pooled estimates were limited by extreme heterogeneity. At the individual trial level, sotatercept (0.7 mg/kg), riociguat (2.5 mg), and metformin (500 mg with bosentan) showed the most favourable benefit profiles. Standardised trial designs and consistent outcome reporting are needed to confirm these potential disease-modifying effects.
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42677064PMC13527792What OpenQuestion holds
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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.