Upfront macitentan and riociguat combo in intermediate-risk idiopathic PAH cut pro-BNP by 61%, improved 6MWD by 51m, and improved hemodynamics at 6 months.
Does upfront combination therapy with macitentan and riociguat improve clinical, echocardiographic, and hemodynamic parameters in patients with newly diagnosed idiopathic PAH at intermediate risk?
Upfront combination therapy with macitentan and riociguat in newly diagnosed intermediate-risk idiopathic PAH appears safe and significantly improves hemodynamics, functional capacity, and risk profile at 6 months.
Absolute Event Rate: 0% vs 0%
Abstract Background According to the current guidelines on pulmonary hypertension the use of riociguat may be considered in patients with idiopathic pulmonary arterial hypertension (PAH) who present at intermediate-low risk of death during the follow-up, while receiving endothelin receptor antagonist and phosphodiesterase-5 inhibitor (PDE5i) therapy, switching from PDE5i to riociguat. Aim of this study was to evaluate the efficacy and the safety of initial combination therapy with macitentan and riociguat in patients newly diagnosed with idiopathic PAH at intermediate risk. Methods In this open-label study we enrolled in a single tertiary centre all consecutive patients with newly diagnosed idiopathic PAH from January to December 2023. We evaluated the risk profile and collected clinical data, pro-brain natriuretic peptide (pro-BNP), six-minute walk distance (6MWD), echocardiographic data and haemodynamics at baseline and at six-month follow-up. Survival and transplantation status were analysed over 18 months. Results We enrolled 25 patients, 17/25 (68%) women, age 58±7. Results are showed in table 1. All patients were at intermediate risk at baseline evaluation. All were treated with macitentan and riociguat as up-front double oral combination therapy. At six-month follow-up pro-BNP decreased of 61% (375±258 vs 951±312 pg/ml, p=0.001) and 6MWD increased of 51 m (p=0.001). At echocardiographic evaluation, right atrial area decreased (18±4 vs 23±7 cm2, p=0.001), and TAPSE (18±4 vs 16±4 mm, p=0.020) and TAPSE/sPAP, (0.35±0.12 vs 0.23±0.07 mm/mmHg, p0.001) increased. Haemodynamics showed a reduction of right atrial pressure (6±4 vs 9±4 mmHg, p=0.014), mean pulmonary pressure (32±10 vs 45±11 mmHg, p0.001) and pulmonary vascular resistance (4.5±2.9 vs 7.3±2.1 Wood Units, p0.001), and an increase of cardiac index (3.4±0.9 vs 2.9±0.7 l/min/m2, p=0.001) and stroke volume index (46±16 vs 36±8 ml/m2, p=0.001). At baseline all patients were at intermediate risk (3 strata model), and at six-month follow-up 16/25 patients (64%) were at low and 9/25 (36%) at intermediate-low risk (4 strata model). There were no serious side effects. No patient discontinued the double oral therapy and 20/25 (80%) reached the maximum dose of riociguat (2.5 mg tid). Two patients died during the follow-up due to causes unrelated to PAH (malignancy and pneumonia). Conclusion These preliminary data support the safety and the efficacy of initial macitentan and riociguat combination therapy in patients with idiopathic PAH. Larger randomized trials are warranted to extend this approach to clinical practice.Table 1
D'Alto et al. (Sat,) reported a other. Upfront macitentan and riociguat combo in intermediate-risk idiopathic PAH cut pro-BNP by 61%, improved 6MWD by 51m, and improved hemodynamics at 6 months.