Targeting Novel Pathways in Pulmonary Arterial Hypertension: A Systematic Review and Meta-Analysis of New Therapeutic Agents
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…
How strong is the evidence?
Evidence Hub reads this as a meta-analysis, done in people. Its evidence level is 1 of 5 (Highest · pooled evidence). Pooled evidence from several studies sits at the top of the evidence pyramid. Reported size: 1,782 participants or records.
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