Patients newly diagnosed with pulmonary arterial hypertension (PAH) treated with macitentan and tadalafil combination therapy showed hemodynamic progress, as well as improvements in function and risk profile, according to Olivier Sitbon, MD, PhD, from Université Paris-Sud, who will present the study findings at the CHEST Annual Meeting 2019 in New Orleans.
PAH is a chronic disease caused by elevated blood pressure and resistance in the blood vessels of the lungs. Current guidelines recommend early treatment with an endothelin-receptor antagonist (ERA) and a phosphodiesterase type-5 inhibitor (PDE-5).
Macitentan, an endothelin-receptor antagonist, reduces production of endothelin, decreasing lung blood vessel constriction and lowering blood pressure in the pulmonary arteries. Phosphodiesterase type-5 inhibitors, such as tadalafil, are used as targeted therapy to slow pulmonary hypertension progression and, in some cases, reverse some heart and lung damage.
The researchers evaluated 46 newly diagnosed, treatment-naive adult PAH patients with medium functional ability who enrolled in the OPTIMA trial, a prospective, multicenter, single-arm, open-label, phase IV trial designed to evaluate the efficacy, safety and tolerability of initial oral combination therapy using macitentan and tadalafil.
Using data from week 16, the investigators found that macitentan and tadalafil combination therapy eased blood circulation in the lungs by 47%. The mean six-minute walk distance increased by 35.8 meters. Approximately 63% of patients had improvement in their functional ability. The patients tolerated the treatment well.
"Our findings add new evidence to the benefit of initial oral double combination therapy in patients with pulmonary hypertension," concluded Dr. Sitbon.
Victor Test, MD, Co-Chair of the CHEST Scientific Program Committee and Professor of Texas Tech University Health Sciences Center, addressed the overall importance of the study: "This study examines upfront combination therapy with macitentan plus tadalafil. Over the 16-week period, there was a functional improvement as well as hemodynamic parameters. In addition, the combination therapy resulted in a reduction in high-risk parameters. This study is encouraging regarding the dual upfront therapy with these agents in patients with PAH. It should not be considered an equivalent trial to longer morbidity-driven endpoint studies, but it is a positive trial that is encouraging. This study adds additional strength to the evidence for upfront dual oral therapy."