Abstract 4146364: A refined definition for low-risk pulmonary arterial hypertension patients including mortality and morbidity

Background: According to the European Guidelines, “low-risk” pulmonary arterial hypertension (PAH) patients is defined as a risk of death < 5% within a year and represents a treatment-goal. However, the impact of morbidity (e.g. hospitalization and clinical worsening), were not included in this definition. Research Questions: Can REVEAL 2.0 risk score further identify low-risk PAH patients for both morbidity and mortality? Aims: Using the REVEAL 2.0 risk score, to propose a modified definition of “low-risk” to include the risk of both morbidity and mortality at 1- and 3-years, respectively. Methods: A harmonized dataset from 8 PAH randomized controlled trials from the FDA was used for this analysis and REVEAL 2.0 risk score was calculated for each patient. Modified low-risk was a priori defined by “risk of death ≤ 5% at 3-years and risk of clinical worsening ≤10% at 1-year”. Clinical worsening was defined as any of the following: lung transplantation or hospitalization due to PAH worsening, initiation of prostanoids/chronic oxygen, 15% decrease in 6-MWD from baseline, a worsening of NYHA, addition of a new PAH medication. Results: A total of 4,122 PAH patients were included: median age 49 (36, 62) yo, mPAP 50 (40, 60) mmHg, PVR 10 (7, 14) WU, 6MWD 375 (306, 423) m, NTproBNP 884 (230, 3010) pg/mL. Patients with a REVEAL 2.0 risk score ≤ 4 had a 1-year clinical worsening free-survival and 3-year survival rate of 92% and 95% ( Figure 1 ). The 3-years survival was significantly better in patients with a REVEAL 2.0 ≤ 4 compared to 5-6: HR=0.47, 95%CI[0.27-0.84], p=0.01. Compared to patients with REVEAL 2.0 risk score of 5-6 (“classical” low-risk), those with a REVEAL 2.0 risk score ≤ 4 (“refined low-risk”) had a better clinical, biological, hemodynamic presentation, and outcomes ( Table 1 ). Conclusion: This study is the first embedding both morbidity and mortality within the definition of low risk for PAH patients and suggests that PAH patients with REVEAL 2.0 risk score ≤ 4 meet this definition. This definition may be a promising new treatment-goal strategy in future randomized controlled trials but also for daily clinical practice.