Refining the Definition for “Low Risk” in Pulmonary Arterial Hypertension

Background “Low-risk” pulmonary arterial hypertension (PAH) patients are defined as having a risk of death <5% within 1 year. As treatment improves, accounting for the negative impact of short-term morbidity and considering extending the duration of <5% mortality in this definition seem prudent. Objectives This study sought to propose a more stringent definition of low risk that extends the low mortality risk to 3 years and specifies a low risk of morbidity at 1 year. Methods This study used patient-level data from a harmonized data set of 8 PAH randomized controlled trials that included patients with a REVEAL (Registry to Evaluate Early and Long-Term PAH Disease Management) 2.0 risk score ≤6 (ie, low risk using contemporary scores). Low risk was a priori defined as “risk of death <5% at 3 years and risk of clinical worsening <10% at 1 year.” Clinical worsening was defined at the individual trial level and included any of the following: lung transplantation, hospitalization for PAH, initiation of long-term oxygen therapy, 15% decrease in 6-minute walking distance (6MWD) from baseline with a worsening of NYHA functional class, or the addition of a new PAH medication. Results A total of 1,925 PAH patients were included: median age, 46 years (Q1-Q3: 34-57 years); mean pulmonary artery pressure, 47 mm Hg (Q1-Q3: 37-58 mm Hg); pulmonary vascular resistance, 8 WU (Q1-Q3: 6-12 WU), 6MWD, 409 m (Q1-Q3: 363-423 m); and N-terminal pro–B-type natriuretic peptide, 227 pg/mL (Q1-Q3: 101-621 pg/mL). Compared with patients with a REVEAL 2.0 score equal to 5 or 6, patients with a score ≤4 had a better clinical and hemodynamic presentation and met the definition of “refined low risk” (3-year mortality of 2.6% and 1-year clinical worsening of 6.4%). Idiopathic PAH, 6MWD, N-terminal pro–B-type natriuretic peptide, NYHA functional class I to II, heart rate, and the absence of previous atrial fibrillation were associated with refined low risk. Conclusions This study is the first to embed both morbidity and mortality within the definition of low -risk for PAH and suggests that patients with a REVEAL 2.0 risk score ≤4 define this condition.