Macitentan-tadalafil combination therapy effective in PAH: Analysis
Similar efficacy found for patients with or without some heart problems
For people with pulmonary arterial hypertension (PAH) both with and without a few co-occurring heart problems, combination therapy with macitentan and tadalafil is similarly effective, according to a new analysis by researchers in the U.S. and Europe.
“Initial combination therapy with macitentan plus tadalafil is efficacious in patients with PAH with up to two cardiac comorbidities [coexisting disorders] and those without, with similar safety and tolerability profiles between the two subgroups,” the researchers wrote.
The study, “Initial combination therapy with macitentan and tadalafil in patients with pulmonary arterial hypertension, with and without cardiac comorbidities,” was published in the European Journal of Heart Failure. The work was funded by Actelion Pharmaceuticals, a subsidiary of Johnson & Johnson; two of the 14 researchers work for Actelion in Switzerland.
Macitentan and tadalafil are both medications that act to relax and widen blood vessels, thus helping to reduce blood pressure. Both therapies are available individually: macitentan is sold under the brand name Opsumit by Actelion, while tadalafil is marketed as Adcirca (sold by United Therapeutics in the U.S. and by Eli Lilly in Europe).
Johnson & Johnson also has developed a tablet that combines both therapies, recently approved in the U.S. under the name Opsynvi and currently up for approval in Europe under the name Yuvanci.
Combination therapy found safe, well tolerated for PAH patients
PAH is marked by high blood pressure in the lungs, which puts abnormal strain on the heart. People with PAH frequently have heart-related comorbidities, or co-occurring health problems, like diabetes, high blood pressure, or coronary heart disease. Combination therapy with macitentan and tadalafil is generally recommended for PAH patients — but now, a team of researchers considered whether this combo works as well in patients with heart comorbidities as among those without.
To answer that question, the team conducted an analysis using data from two completed clinical trials, TRITON (NCT02558231) and REPAIR (NCT02310672). In both studies, PAH patients were given both therapies as an initial treatment.
The analysis included data on nearly 150 PAH patients who were given treatment with both therapies. Among them, 62 had no cardiac comorbidities and 78 had one or two comorbidities. (PAH patients with three or more comorbidities are generally not eligible for trials, so were not included in this analysis.)
To measure the efficacy of the combination therapy, the researchers looked at its effect on pulmonary vascular resistance — a measure of how much force it takes to push blood through the lungs’ vessels. The results showed that, after six months on macitentan and tadalafil together, both groups showed similar average improvements, or reductions in assessments: 55% for those without comorbidities and 50% for those with comorbidities.
These analyses show that initial double oral combination therapy with macitentan and tadalafil is effective, safe and well-tolerated in PAH patients including in those with 1-2 cardiac comorbidities [co-occurring conditions]. … Marked … improvements … were observed, regardless of comorbidity status.
Other measures of blood flow dynamics and heart health also showed similar improvements in both groups, and safety outcomes were comparable as well. For the six-minute walk distance, a common test of exercise capacity, patients with comorbidities had somewhat less dramatic improvements, but both groups nonetheless experienced significant improvements in this measure.
“These analyses show that initial double oral combination therapy with macitentan and tadalafil is effective, safe and well-tolerated in PAH patients including in those with 1-2 cardiac comorbidities,” the researchers wrote. “Marked … improvements … were observed, regardless of comorbidity status.”
About the Author
