In PAH, Macitentan-Tadalafil Combination Therapy Is Effective, Tolerable

Initial oral combination therapy with macitentan and tadalafil may provide hemodynamic and functional benefits to individuals recently diagnosed with pulmonary arterial hypertension (PAH), according to results from the OPTIMA phase 4 trial.

To evaluate the efficacy, safety, and tolerability of the combination therapy for PAH treatment, the authors enrolled 46 patients into the multicenter, single-arm, open-label OPTIMA trial. The participants—who were all treatment-naïve adults in World Health Organization functional class 2 or 3—received macitentan, 10 mg, and tadalafil, 20 mg, once daily. After 8±3 days, the tadalafil dose was increased to 40 mg, once daily.


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At week 16, the researchers assessed for efficacy and determined that the primary endpoint of mean pulmonary vascular resistance was reduced by 47.0% from baseline. The percentage of participants who met at least 3 low-risk criteria increased from baseline (23.9%) to week 16 (68.2%).

The researchers monitored the safety of the macitentan-tadalafil combination until study end, with the median duration of exposure to the combination being 605.5 days. Of the total 46 participants, 43 had reported at least 1 adverse event (AE); the most common AEs were peripheral edema, headache, diarrhea, dyspnea, anemia, and asthenia. 

Of the participants who had an AE, 13 had a serious AE, and 3 discontinued treatment due to the AE. Three participants had died due to cardiac arrest, heart failure, or multiorgan failure with sepsis.

Furthermore, 4 participants had a decrease in hemoglobin below 10 g/dL, and 1 participant had aminotransferases 3 times or greater than the upper limit of normal.

“In OPTIMA, initial macitentan and tadalafil combination therapy was well tolerated in patients with PAH and led to hemodynamic improvement, as well as improvements in functional parameters and risk profile,” the researchers concluded.

—Colleen Murphy


Sitbon O, Canuet M, Picard F, et al. Initial treatment combination with macitentan and tadalafil in patients with pulmonary arterial hypertension: results from the OPTIMA study. Chest. 156(4 Suppl):A870-A871. doi:10.1016/j.chest.2019.08.825