Historical milestones and future horizons: exploring the diagnosis and treatment evolution of the pulmonary arterial hypertension in adults

INTRODUCTION: Pulmonary hypertension is a life-threatening condition characterized by elevated mean pulmonary arterial pressure and vascular resistance. Significant advances in diagnosis and treatment have been achieved over the 20th and 21st centuries, yet challenges remain in improving long-term outcomes. AREAS COVERED: This review discusses the historical milestones in understanding and pharmacotherapy of the pulmonary arterial hypertension (PAH). A comprehensive literature search was conducted to explore the earliest reports of each approved medication for pulmonary hypertension, along with historical papers detailing the pathophysiological and diagnostic development. Additionally, the search aimed to identify novel therapeutic strategies, including repositioned drugs and emerging targets. EXPERT OPINION: While current therapies, such as prostacyclin analogs and PDE5 inhibitors, improve functional capacity and hemodynamics, they face limitations, including costs, administration, and a predominantly vasodilatory approach. Additionally, the limitations of current clinical trial designs for rare diseases like pulmonary arterial hypertension hinder the evaluation of potentially effective drugs. These challenges underscore the urgent need for translational research to optimize trial methodologies, accelerating the development of new therapies. Innovative approaches, such as drug repositioning and the exploration of novel molecular targets, are critical to overcoming these barriers and ensuring timely, effective, and affordable treatment options for patients with PAH.