Rasheed Amir, Aslam Shadab, Sadiq Hafiz Zeeshan, Ali Salamat, Syed Rizwana, Panjiyar Binay K
Internal Medicine, Aziz Bhatti Shaheed Teaching Hospital, Gujrat, PAK.
Internal Medicine, Jinnah Hospital, Lahore, PAK.
Cureus. 2024 Aug 29;16(8):e68117. doi: 10.7759/cureus.68117. eCollection 2024 Aug.
Pulmonary arterial hypertension (PAH) is a serious, progressive, and potentially fatal lung disease characterized by a gradual increase in mean pulmonary arterial pressure to over 20 mmHg at rest. The pathogenesis of PAH is multifactorial. It involves dynamic obstruction of the pulmonary vasculature through vasoconstriction, structural obstruction due to adverse vascular remodeling, and pathological obstruction caused by vascular fibrosis and stiffening, which reduces compliance. PAH often presents with vague initial symptoms and is frequently diagnosed at an advanced stage. The increased pulmonary arterial pressure leads to vascular remodeling, eventually resulting in right ventricular hypertrophy and failure. PAH is a rare condition with a median life expectancy of three years, underscoring the need for effective treatment alternatives. Several FDA-approved therapeutic options are available, including prostacyclin analogs (epoprostenol, iloprost, and treprostinil), the non-prostanoid IP receptor agonist selexipag, selective endothelin receptor antagonists (ERA) (ambrisentan, bosentan, and macitentan), phosphodiesterase 5 inhibitors (sildenafil and tadalafil), and the soluble guanylate cyclase (sGC) stimulator riociguat. Despite these advancements, current medications do not provide a permanent cure. This study presents an overview of current and emerging PAH therapies through a systematic literature review. It involved an analysis of nine studies and a review of 800 papers from reputable journals published between 2013 and June 2023. The research focused on drug effects on the six-minute walk distance (6-MWD) and associated side effects in randomized controlled trials. The review found that while udenafil, imatinib, racecadotril, sotatercept, anastrozole, riociguat, tacrolimus, and ralinepag were evaluated, imatinib was notably associated with adverse side effects. Conversely, udenafil, racecadotril, sotatercept, anastrozole, riociguat, tacrolimus, and ralinepag were found to be safe, well-tolerated, and effective in improving hemodynamic measures and 6-MWDs. This study aims to summarize the developing treatment options currently under clinical trials, highlighting the need for further trials before their application in clinical practice.
肺动脉高压（PAH）是一种严重、进行性且可能致命的肺部疾病，其特征是静息时平均肺动脉压逐渐升高至超过20 mmHg。PAH的发病机制是多因素的。它涉及通过血管收缩导致的肺血管动态阻塞、由于不良血管重塑引起的结构阻塞以及由血管纤维化和硬化导致的病理阻塞，从而降低顺应性。PAH通常最初症状不明确，且常被诊断为晚期。肺动脉压升高导致血管重塑，最终导致右心室肥厚和衰竭。PAH是一种罕见疾病，中位预期寿命为三年，这凸显了有效治疗方案的必要性。有几种FDA批准的治疗选择，包括前列环素类似物（依前列醇、伊洛前列素和曲前列尼尔）、非前列腺素IP受体激动剂司来帕格、选择性内皮素受体拮抗剂（ERA）（安立生坦、波生坦和马昔腾坦）、磷酸二酯酶5抑制剂（西地那非和他达拉非）以及可溶性鸟苷酸环化酶（sGC）刺激剂利奥西呱。尽管有这些进展，但目前的药物并不能提供永久性治愈。本研究通过系统的文献综述概述了当前和新兴的PAH治疗方法。它涉及对九项研究的分析以及对2013年至2023年6月期间著名期刊发表的800篇论文的综述。该研究重点关注随机对照试验中药物对六分钟步行距离（6-MWD）的影响及相关副作用。综述发现，虽然对乌地那非、伊马替尼、消旋卡多曲、索他洛尔、阿那曲唑、利奥西呱、他克莫司和拉尼帕格进行了评估，但伊马替尼明显与不良副作用相关。相反，发现乌地那非、消旋卡多曲、索他洛尔、阿那曲唑、利奥西呱、他克莫司和拉尼帕格是安全的，耐受性良好，并且在改善血流动力学指标和6-MWD方面有效。本研究旨在总结目前正在进行临床试验的不断发展的治疗选择，强调在其应用于临床实践之前需要进一步试验。
