Changes in REVEAL risk score in patients with pulmonary arterial hypertension treated with macitentan in clinical practice: results from the PRACMA study
Authors: Escribano-Subias Pilar , López Raquel , Almenar Luis , Lázaro María , Forn Ian , Torrent Anna , Blanco Isabel , Barberà Joan Albert ,   on behalf of the PRACMA investigators, Almenar Luis , Dobaño José Manuel Alvarez , Baloira Adolfo , Barbado Julia , Diaz Pedro Bedate , Blanco Isabel , Blanquer David , Ruiz Ana José Bustamante , Cadenas Sergio , Casado Ignacio , Chamorro Carlos , Cifrian José Manuel , Cremer David , Delgado Eva , Delgado Juan Luis , Domingo Juan Antonio , Escribano Pilar , Arangüena Luis García , Muñoz Juan Pablo García , Iturbe David , Lara Antonio , Lázaro María , Meseguer Manuel López , López Raquel , Madroñero Ana , Marín Adela , Ferragut Lluis Molina , Escobar Eduardo Moreno , Núñez Ana , de Saracho y Bobo Juan Ortiz , Peralta Cilia Amparo , Peñate Gregorio Pérez , Amigó Javier Pomares , Rodriguez Carlos , Roig Vicente , Rueda Ximo , Sala Ernest , Simón Rafaela Sánchez 
Published: June 2020

Abstract
Background
Macitentan is a dual endothelin receptor antagonist indicated for the long-term treatment of pulmonary arterial hypertension (PAH). We evaluated the change over time in REVEAL risk score in incident and prevalent patients receiving macitentan for the first time.

Methods
Retrospective, observational study including adult patients with idiopathic/heritable PAH or PAH associated with connective tissue disorders or congenital heart disease treated with macitentan for ≥6-month follow-up in Spain. The REVEAL risk score and risk strata were computed at the start of macitentan and after ≥6-month in patients with ≥7 out of 12 valid REVEAL components.

Results
Overall, 81 patients (57 for the REVEAL score) were analysed, 77.8% women. The mean age was 57.2 years and 50.6% of patients had idiopathic/heritable PAH. Prevalent patients were 59.3 and 40.7% were incident. Main therapies for PAH included macitentan monotherapy (42.0%) and macitentan in combination with phosphodiesterase type 5 inhibitor (44.4%). With a median time of macitentan treatment of 10.5 months, the mean REVEAL score was 8.7 points at baseline and was 7.2 points after ≥6-month follow-up. The mean change (95% CI) in REVEAL risk score was − 1.4 (− 2.0, − 0.9) points (p < 0.0001), being − 1.8 (− 3.0, − 0.7) points (p = 0.0040) and − 1.2 (− 1.8, − 0.5) points (p = 0.0010), in incident and prevalent patients, respectively. The reduction was also significant by risk stratum (36.8% of patients in the high-very high risk strata at baseline versus 14.0% after ≥6-month, p < 0.05) and therapy group. The REVEAL components that significantly improved were WHO functional class (FC) (63.9% FC III at macitentan initiation and 23.6% after ≥6-month, p < 0.0001), 6-min walk test (mean change: 41.8 m, p < 0.01), brain natriuretic peptide (BNP) or N-terminal proBNP (NT-proBNP) (mean change of − 157.6 pg/mL and − 530.0 pg/mL, respectively, p < 0.05 both), and pulmonary vascular resistance (PVR) (mean change: − 3.4 WU, p < 0.01).

Conclusions
In this study, treatment with macitentan improved the REVEAL risk strata and score in both incident and prevalent PAH patients, and in all patients regardless of the therapy strategy. Macitentan significantly improved some of REVEAL components including WHO FC, BNP/NT-proBNP, PVR, and 6-min walk test after at least 6-month follow-up.