Exploring the Economic Burden of Pulmonary Arterial Hypertension and Its Relation to Disease Severity and Treatment Escalation: A Systematic Literature Review

Background Pulmonary arterial hypertension (PAH) is a highly progressive disease characterized by luminal narrowing of the pulmonary arteries, leading to progressive dyspnoea and restricted functional capacity, which can ultimately result in right ventricular failure and death. Treatment goals include improving functional class and walk distance, recovering right ventricular function, halting disease progression, and improving survival. PAH carries a high mortality rate, and treatment escalation is a common feature of disease management. Due to the substantial impact of PAH, a high economic burden has been observed. A systematic literature review (SLR) was carried out to assess the contemporary economic burden of PAH, including the impact of disease severity and treatment escalation. Methods An electronic database search was conducted and supplemented with a hand search of health technology assessments and conference materials. Studies were included from 2012 to 2024, with no restrictions on geographical location. The inclusion criteria specified that adult patients with PAH (≥ 18 years) and only English language studies were captured. Results The review included 148 studies and evaluations, 110 of which were observational studies, 14 were economic evaluations, and 24 were health technology assessments. The studies identified reported on several healthcare resource utilization (HCRU) outcomes including hospitalization, PAH-related hospitalization, inpatient visits, emergency department (ED) visits, intensive care unit (ICU) visits, and outpatient visits. Cost data were also reported, including total costs and costs for each of the above-mentioned types of HCRU, as well as specific costs such as pharmacy and drug costs. The results provide an overview of the high economic burden caused by PAH, indicating that the economic burden increases with increasing severity; reported mean monthly costs were as high as US $14,614 (cost converted to USD 2024) for the highest severity group. These data also demonstrated the impact of PAH-specific therapies in reducing HCRU, with efficacious treatment shifting management from an inpatient to outpatient setting (i.e., reduced inpatient admissions and length of stay). Further, while treatment escalation resulted in increased pharmacy costs, this was offset by a reduction in HCRU, including hospitalizations and ED visits. Timely diagnosis was also associated with reduced economic burden, as patients with a longer delay prior to diagnosis reported a higher mean number of monthly hospitalizations, ICU stays, and ED visits. Functional limitation is a common feature of PAH disease progression and can severely impact a patient’s ability to work. This SLR identified few studies that investigated such outcomes as well as broader indirect costs, such as out-of-pocket costs and productivity loss. Discussion This study highlights the considerable economic burden associated with PAH, which is particularly evident for HCRU, and the importance of effective disease management in reducing this burden. Additionally, these findings demonstrate the economic value of treatment escalation and suggest higher drug costs can potentially be offset through improved patient outcomes and associated reductions in HCRU.