Overview of Systematic Reviews on Treatments for Pulmonary Arterial Hypertension: Assessing Methodological Quality and Mapping Evidence Gaps.

Background: Higher quality scaled-up evidence on pulmonary arterial hypertension (PAH), a rare and life-threatening disease, is needed to support informed decision-making. We aimed to map the current knowledge of PAH treatments and evaluate the methodological quality of published systematic reviews.

Methods: An overview with literature searches in PubMed and Embase (May 2025) was performed (CRD42023414469). The methodological and reporting quality of the eligible records was assessed using A Measurement Tool to Assess Systematic Reviews (AMSTAR 2) and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 checklist, respectively. Association analyses between tools' scores with key variables (article publication date, journal impact factor, country/region) were performed (SPSS v.28). An evidence map summarizing the most reported treatments and outcomes was also built.

Results: Overall, 57 systematic reviews (n = 52; 91.2% with meta-analysis) published between 1997 and 2025 (median year 2017), authored mostly by countries from Asia (n = 35; 61.4%) and North America (n = 12; 21.1%), were included. The classes of phosphodiesterase type-5 inhibitors, endothelin receptor antagonists, and prostanoids and combination therapies were each assessed in one-third of the studies each. Over 20 different outcomes were reported, with the most common surrogate endpoints being 6-min walking distance (n = 42; 73.7%) and mean pulmonary arterial pressure (n = 33; 57.9%). Most studies were classified as having critically low methodological quality (n = 48; 84.2%), with only three presenting high-quality methodology according to AMSTAR 2. The mean PRISMA score was 21.3 ± 2.9, indicating an adherence rate of 78.9% to the checklist among authors. Although there was an improvement over time in the quality of the reviews (p = 0.016 for AMSTAR; p = 0.002 for PRISMA), no correlations were found based on country nor journal impact factor.

Conclusions: Methodological weaknesses remain common in systematic reviews of PAH; therefore, enforcing compliance with guidelines and standardizing outcome measurements through a core outcome set is crucial for improving data comparability and clinical application.

Registration: PROSPERO identifier no. CRD42023414469.