Combination therapy effective in PAH with heart disease risk factors
Real-world analysis looks at macitentan-tadalafil combination
People with pulmonary arterial hypertension (PAH) with at least one coexisting condition associated with cardiovascular disease had similar rates of hospitalization and mortality as those without these conditions after a combination treatment of macitentan and tadalafil, according to a real-world analysis.
There was, however, a tendency towards more adverse events in patients with several coexisting health conditions, also called comorbidities, and in those with such conditions who were newly diagnosed and started on combination therapy.
“These data provide real-world evidence to suggest that a more proactive approach to the use of combination therapy may be considered for patients with PAH and cardiovascular comorbidities,” the researchers wrote.
The study, “Macitentan and Tadalafil Combination Therapy in Patients with Pulmonary Arterial Hypertension and Cardiovascular Comorbidities: Real-World Evidence from OPUS and OrPHeUS,” was published in Advances in Therapy.
People with PAH, or high blood pressure in the lungs, often have diabetes, systemic (bodywide) high blood pressure, and/or obesity, all of which are risk factors for cardiovascular disease (CVD), conditions that affect the heart or blood vessels. It’s recommended that PAH patients with such comorbidities start with one PAH medication and then escalate to a second treatment if needed.
Clinical trials suggest combination therapy effective
Two treatments for these patients are macitentan and tadalafil, both of which work to reduce blood pressure by relaxing and widening blood vessels. Macitentan is sold under the brand name Opsumit, and tadalafil is marketed as Adcirca. A fixed-dose combination of both medicines is sold as Opsynvi for PAH patients in World Health Organization functional class 2 or 3.
A recent analysis of data from two clinical trials suggested that a combination of macitentan and tadalafil was similarly effective in PAH patients with and without CVD comorbidities. However, real-world data is limited, the researchers said.
The team collected data from two real-world studies of patients newly treated with macitentan: OPUS (NCT02126943), the OPsumit USers Registry, and OrPHeUS (NCT03197688), the Opsumit Historical Users study that was launched to supplement OPUS data. The work was funded by Actelion Pharmaceuticals, part of Johnson & Johnson, which markets Opsumit.
In total, 1,336 PAH patients received macitentan plus tadalafil. More than half (61.4%) had at least one CVD comorbidity: diabetes, systemic high blood pressure, or obesity.
Patients with such comorbidities were more likely to be functionally impaired, have high levels of markers for heart disease, and have idiopathic PAH, in which the cause is unknown. In comparison, those without CVD comorbidities were more likely to have PAH related to connective tissue disease or congenital heart disease. Blood flow test results were similar between the two groups.
After 14-15 months of the combination therapy, slightly fewer patients with at least one comorbidity were hospitalized for any cause than those without (40% vs. 45.2%). A one-year estimate for the proportion of PAH patients free from all-cause hospitalization was comparable between the two groups (63.6% vs. 60%).
The proportion of patients who died was similar in those with and without at least one CVD comorbidity (12.4% vs. 14.2%). Survival estimates between the two groups were comparable at one year (92.3% vs. 91.9%), two years (85.4% vs. 82.8%), and three years (77.8% vs. 72.9%).
The rates of all-cause hospitalization and mortality were similar among those with one, two, or three CVD comorbidities, as well as treatment-naïve patients who received the combination as a first-line treatment. Still, the rate of all-cause hospitalization, but not mortality, was higher among treatment-naïve patients than in the overall population.
Similar proportions of PAH patients with and without at least one CVD comorbidity discontinued combination therapy. The likelihood, with or without CVD signs, of patients remaining on the combination therapy dropped at one year (66.5% vs. 68.5%) and two years (55.4% vs. 52.6%).
In OPUS, the proportion of patients experiencing an adverse or a serious adverse event was comparable between the two groups. These were most commonly shortness of breath (dyspnea), headache, nausea, and diarrhea. There was a trend toward a higher incidence of adverse events with more comorbidities and in PAH patients with at least one CVD sign who were new to treatment.
“Patients with PAH and cardiovascular comorbidities treated with macitentan and tadalafil combination therapy had similar results as those without cardiovascular comorbidities,” the authors concluded. “This suggests that combination therapy may be used in select patients with PAH and cardiovascular comorbidities, although those who have more comorbidities or are new to PAH treatment may need closer observation.”
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