Why Wait for Sick People to Get Sicker? The Paradox of the Treatment of Patients With Pulmonary Arterial Hypertension

Pulmonary arterial hypertension (PAH) is a chronic, progressive, and ultimately life-threatening disease characterized by vascular remodeling and increasing pulmonary vascular resistance. Despite significant advances in diagnostic tools and therapeutic strategies, clinical intervention often begins only when patients become symptomatic-typically at New York Heart Association (NYHA) functional class II or higher. Paradoxically, while early detection of PAH is strongly encouraged to preempt irreversible vascular, cardiac, and multisystem damage, treatment remains largely restricted to those already exhibiting symptoms. Patients in NYHA class I, though experiencing pathophysiological progression, are systematically excluded from approved pharmacological therapies. This disjunction represents not only a clinical and ethical conundrum but also a conceptual paradox: why invest in early diagnosis if early treatment is withheld? Emerging evidence on various chronic diseases, including cancer, infectious diseases like HIV and hepatitis, and even other cardiovascular diseases, underscores the benefits of initiating treatment before the onset of symptoms. In contrast, the current approach to PAH inadvertently promotes a nihilistic "wait and see" policy, exposing asymptomatic patients to preventable deterioration. Herein, we call for a reassessment of clinical guidelines, regulatory frameworks, and access policies with the goal of better aligning them with the biological realities of PAH. While we advocate for a paradigm shift toward the inclusion of NYHA class I patients in treatment strategies, we explicitly acknowledge the current limitations of the evidence base and emphasize the need for ongoing, high-quality research including counterarguments and the practical challenges of early treatments.