The following is a summary of “Randomized Trial of Macitentan/Tadalafil Single-Tablet Combination Therapy for Pulmonary Arterial Hypertension,” published in the January 2024 issue of Cardiology by Grünig et al.

Combining endothelin receptor antagonist (ERA) and phosphodiesterase 5 inhibitor (PDE5i) is advised for low to intermediate-risk pulmonary arterial hypertension (PAH) patients. A convenient once-daily single tablet of ERA macitentan and PDE5i tadalafil fixed-dose combination (M/T FDC) would streamline treatment. 

Researchers conducted a retrospective phase 3 A DUE study to assess the efficacy and safety of M/T FDC compared to macitentan 10 mg and tadalafil 40 mg monotherapies in PAH patients, encompassing those who were treatment-naïve and those previously treated with ERA or PDE5i monotherapies.

They randomized WHO functional class II-III patients based on their PAH treatment history (treatment-naïve, ERA, or PDE5i monotherapy) at baseline to receive M/T FDC, macitentan, or tadalafil. The primary endpoint assessed was the change in pulmonary vascular resistance (PVR) at week 16.

The results showed that out of a total of 187 patients,(n = 108), macitentan (n = 35), or tadalafil (n = 44). The reduction in PVR with M/T FDC was significantly greater compared to macitentan (29%; geometric mean ratio 0.71; 95% CL: 0.61-0.82; P<0.0001) and tadalafil (28%; geometric mean ratio 0.72; 95% CL: 0.64-0.80; P<0.0001). Three patients in the M/T FDC arm died, but their deaths were judged unrelated to treatment. AEs leading to discontinuation, serious AEs, and those of special interest (such as anemia, hypotension, and edema) were more frequent with M/T FDC.

Investigators concluded that M/T FDC effectively reduces PVR, offers a convenient single-tablet option, and could be a promising initial or escalated treatment for PAH.

Source: jacc.org/doi/10.1016/j.jacc.2023.10.045