Modern Treatment of Pulmonary Hypertension

Abstract

Pulmonary arterial hypertension (PAH) is a progressive, life-threatening cardiovascular disease marked by proliferative remodeling of the small pulmonary arteries and progressive narrowing of their lumen. A delayed diagnosis leads to heart failure. A systematic review and meta-analysis synthesizing evidence from 17 Phase III randomized controlled trials encompassing 8,029 patients with Pulmonary Arterial Hypertension (PAH). It evaluates the shift in clinical paradigms from historical, palliative monotherapy toward early, aggressive multi-pathway combination therapy and novel disease-modifying biological agents. Quantitative results demonstrate a clear efficacy hierarchy: upfront triple combination therapy achieves the highest reduction in pulmonary vascular resistance (-50.0% PVR), while upfront dual oral regimens deliver substantial functional improvements in 6-minute walk distance. The study highlights sotatercept (an activin signaling inhibitor) as a novel agent that achieves direct reverse vascular remodeling, lowering mean pulmonary arterial pressure (-13.9 mmHg) without requiring a compensatory rise in cardiac work. "Treat-to-target" strategy based on 2022 ESC/ERS guidelines to prevent right heart failure and optimize long-term transplant-free survival. .