Abstract
Purpose: Initial combination therapy with ambrisentan and tadalafil has been demonstrated superior to either agent alone in pulmonary arterial hypertension (PAH). More recently, the OPTIMA trial showed efficacy of another combination of endothelin receptor antagonist and phosphodiesterase 5-inhibitor, macitentan and tadalafil, as initial therapy for PAH. The objective of this study was to assess the effectiveness, tolerability, and safety of macitentan and tadalafil in a real-world clinical setting.Methods: This single centre, retrospective cohort study identified adult patients newly diagnosed with PAH between January 2014 and December 2017 who were started on macitentan and tadalafil. Patients were retrospectively followed for one year. Effectiveness was evaluated via change from baseline in disease risk profile based on a validated score incorporating World Health Organization functional class, 6-minute walk distance (6MWD), B-type natriuretic peptide (BNP), and hemodynamics on follow-up right heart catheterization. Secondary endpoints included change in 6MWD, BNP, and hemodynamic variables. Drug tolerability and adverse events were assessed.Results: The cohort included 46 patients, 8 of whom (17%) did not tolerate and discontinued either macitentan or tadalafil. Median time to follow-up was 161 days (IQR 72). 42% of patients with an initially moderate or high risk disease profile improved to low risk. Secondary endpoints showed a reduction in the geometric mean of pulmonary vascular resistance of 45% (95% CI 29, 57%) and improvement in 6MWD of 88m (95% CI 27, 148m).Conclusion: In a real-world setting, macitentan and tadalafil as initial combination therapy for PAH was well tolerated and yielded clinical benefit.
THU0418 Long -term efficacy and safety of monotherapy versus combination therapy in systemic sclerosis-associated pulmonary arterial hypertension (PAH): a retrospective cohort study from the nationwide spanish scleroderma registry (RESCLE)
