What does this research mean for the field?

Only 14% of patients with pulmonary arterial hypertension meet randomized clinical trial criteria, with trial-like patients showing better 5-year survival but no improved prognosis on multivariable analysis. Novelty: ClaimNovelty.CONFIRMATORY. Consensus alignment: ConsensusAlignment.CHALLENGES_CONSENSUS.

What question did this study set out to answer?

This study aims to assess how well clinical trial populations represent real-world patients with pulmonary arterial hypertension.

February 8, 2026

Representativeness of randomized clinical trial criteria among the real-world patients with pulmonary arterial hypertension: an analysis from the FOCUS-PAH registry

Key Result

Only 14% of real-world PAH patients met RCT criteria; trial-like patients had better 5-year survival but trial-like status was not independently linked to prognosis.

Key Points

This study aims to assess how well clinical trial populations represent real-world patients with pulmonary arterial hypertension.
Retrospective analysis of 764 patients from the FOCUS PAH Registry.
Comparison of patients adhering to RCT criteria (labeled as 'trial-like') and those in regular clinical practice.
Assessment of 5-year mortality rates and multivariable Cox regression modelling to evaluate outcomes.
Only 14% of patients were classified as trial-like.
Main exclusion reasons included age and specific hemodynamic parameters.
Trial-like patients showed better survival rates and were more likely to receive dual therapy, but fulfilling trial-like criteria did not improve prognosis in multivariable analysis.

Structured PICO

Does meeting RCT inclusion criteria ('trial-like') associate with improved 5-year survival compared to 'real-world' PAH patients?

Population

764 patients with pulmonary arterial hypertension (PAH) from the FOCUS PAH Registry

Intervention

Meeting inclusion and exclusion criteria of recent PAH clinical trials (AMBITION, STELLAR, GRIPHON, TRITON) and having comparable baseline characteristics ('trial-like')

Comparator

Not meeting the trial-like definition ('real-world' patients)

Outcome

5-years mortalityhard clinical

Only 14% of real-world PAH patients meet the inclusion criteria of contemporary RCTs, highlighting a significant gap in the representativeness of clinical trial populations.

Main Result

Absolute Event Rate: 0% vs 0%

Abstract

Abstract PH is a rare condition associated with high mortality and morbidity. Recent RCT have significantly influenced the management of pulmonary arterial hypertension (PAH), leading to improved outcomes for PAH patients. However, patients enrolled in RCT can differ from those encountered in regular clinical practice, especially considering the profound demographic changes of PAH patients worldwide. In this study we aimed to explore the representativeness of the characteristics of RCT populations in the real-world scenario and we proposed a comparison between patients adherent to RCT criteria and real-world patients. Methods: We retrospectively analysed 764 patients from the FOCUS PAH Registry. Patients who met inclusion and exclusion criteria of the most recent clinical trials (AMBITION, STELLAR, GRIPHON, TRITON) and had main baseline characteristics comparable to those of patients enrolled in these RCT (i.e. included in the weighted average) were defined as "trial-like", whereas the remaining population was defined as "real-world". Proportion of trial-like vs real-world patients was assessed at baseline evaluation in the overall cohort. Reasons for not fulfilling the trial-like definition were investigated. The distribution overtime and across different participating centres was also calculated. Study endpoint was 5-years mortality. A multivariable Cox regression model was fitted to assess the association between the trial-like pattern and the outcome. Results: Of 764 patients analysed, only 107 (14%) were trial-like with no differences overtime and across centers with different patients’ volumes. Main exclusion criteria were age and hemodynamic parameters (PAPm 38 or 63 mmHg, PVR 5.5 or 15.5 WU, PCWP 12 mmHg). Trial like patients were younger, more likely had idiopathic and heritable PAH, had less comorbidities (less systemic hypertension 45% vs 32% p=0.013, less AF at presentation 7% vs 2%, p=0.034). Hemodynamic characteristics and RV impairment were more severe at baseline in trial-like (higher PAPm (49 vs 44 mmHg, p0.0001) and PVR (10 vs 8 WU, p0.0001) and more RV disfunction (55% vs 48%, p=0.059). ESC/ERS baseline "Three-Strata" risk category was worse in trial-like patients. Trial-like patients were more likely treated with upfront double therapy combination (48% vs 32%, p=0.004). 5-year survival was better in trial-like patients (Figure KM) but at multivariable analysis fulfilling the trial like definition was not associated with improved prognosis. Conclusion: In the real-world scenario only 14% of patients were trial-like, even in high-volume centres. The main reasons for not fulfilling the trial-like definition were age and hemodynamic parameters. Trial-like patients were more likely treated with upfront double therapy combination and had a better 5-year survival. Enrichment strategies in future studies design are needed to make RCT more representative of real-world scenarios to better address PAH management.

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