Impact of initial treatment strategy on long-term survival in pulmonary arterial hypertension (PAH)

Abstract

Background: Initial dual combination therapy is superior to monotherapy for lowering the risk of clinical-failure events in patients with PAH. However, the impact of initial treatment strategy on long-term survival is still unknown. Objective: To analyse the effect of initial monotherapy, dual or triple (with IV/SC prostacyclin) combination therapy on survival in newly diagnosed PAH patients. Methods: We analysed 1295 consecutive incident patients with functional class (FC) II-IV idiopathic, heritable, or drug-induced PAH diagnosed between 2006 and 2016 and initiated with PAH-targeted therapy: monotherapy (n=824, 64%), dual combination (n=400, 31%) or triple therapy (n=71, 5%). Survival in each treatment group (mono, dual, triple combination) was compared to predicted survival from the French registry equation (Humbert, et al. Eur Respir J 2010). Uni- and multivariate Cox regression was performed to assess survival according to treatment group. Results: Patients initiated with triple therapy were younger with more severe hemodynamics (PVR 18.6±7.5 vs dual therapy 12.1±5.8 and monotherapy 8.9±4.6 WU). Actual three-year survival was better than predicted in all treatment groups: monotherapy 73% vs 63%, dual therapy 72% vs 57%, triple therapy 90% vs 46%. Adjusting for age, gender, FC, 6-min walk distance, right atrial pressure, and cardiac index, the use of initial triple therapy reduced the risk of death compared to mono or dual therapy (HR 0.35, 95% CI 0.17-0.71, p=0.003). Conclusion: Initial triple therapy with IV/SC prostacyclin may reduce the risk of death in incident patients with PAH. This supports the notion of an aggressive early treatment strategy for newly diagnosed patients.