Pharmacol Rev. 2012 Jul;64(3):583-620. doi: 10.1124/pr.111.005587. Epub 2012 Jun 1.
Pulmonary arterial hypertension (PAH) is a life-threatening and progressive disease of various origins characterized by pulmonary vascular remodeling that leads to increased pulmonary vascular resistance and pulmonary arterial pressure, most often resulting in right-sided heart failure. The most common symptom at presentation is breathlessness, with impaired exercise capacity as a hallmark of the disease. Advances in understanding the pathobiology over the last 2 decades have led to therapies (endothelin receptor antagonists, phosphodiesterase type 5 inhibitors, and prostacyclins or analogs) initially directed at reversing the pulmonary vasoconstriction and more recently directed toward reversing endothelial cell dysfunction and smooth muscle cell proliferation. Despite these advances, disease progression is common even with use of combination regimens targeting multiple mechanistic pathways. Overall 5-year survival for PAH has increased significantly from approximately 30% in the 1980s to approximately 60% at present, yet remains abysmal. This review summarizes the mechanisms of action, clinical data, and regulatory histories of approved PAH therapies and describes the latest agents in late-stage clinical development.
肺动脉高压（PAH）是一种由多种原因引起的危及生命的进行性疾病，其特征为肺血管重构，导致肺血管阻力和肺动脉压增加，最常导致右心衰竭。最常见的临床表现是呼吸困难，运动能力受损是疾病的标志。过去 20 年对病理生理学的深入了解导致了治疗方法（内皮素受体拮抗剂、磷酸二酯酶 5 抑制剂和前列环素或类似物）的出现，最初旨在逆转肺血管收缩，最近则针对逆转内皮细胞功能障碍和平滑肌细胞增殖。尽管取得了这些进展，但即使使用针对多种机制途径的联合治疗方案，疾病仍会进展。总体而言，PAH 的 5 年生存率从 20 世纪 80 年代的约 30%显著提高到目前的约 60%，但仍然很低。本文总结了已批准的 PAH 治疗药物的作用机制、临床数据和监管历史，并描述了晚期临床开发中的最新药物。
