Upfront combination therapy with macitentan plus riociguat has demonstrated effectiveness in patients with pulmonary arterial hypertension (PAH), according to the results of a small retrospective, open-label cohort study conducted between 2014 and 2016. Findings from the study were published in Pulmonary Circulation.

Investigators sought to assess the hemodynamic and clinical effects of combined macitentan and riociguat as first-line treatment for newly diagnosed patients with PAH from their practice at the Mount Sinai Beth Israel Pulmonary Hypertension Program in New York City. Clinical and hemodynamic data were collected from 15 consecutive patients with PAH. All data were obtained at baseline, at visit 1 (median, 4 months), and at visit 2 (median, 12 months). Patient survival and transplantation status were analyzed during a 36-month period.

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Overall, 73.3% (11 of 15) of the patients were women; the mean patient age was 55.8 years (range, 27-82 years). At treatment initiation, 14 of the patients belonged to World Health Organization functional class III (WHO FC III). The last patient, who had systemic lupus erythematosus-PAH, was classified as WHO FC IV because of a history of exertional syncope.

Study results demonstrated a significant increase in 6-minute walk distance from 281.6 m at baseline, to 315.7 m at visit 1, to 313.9 m at visit 2, representing a 34-m and 32-m change, respectively, associated with improvements in Borg score (P <.05). Moreover, significant decreases in brain natriuretic peptide were reported: from 318.2 pg/mL at baseline to 122.0 pg/mL at visit 1, and to 98.6 pg/mL at visit 2 (P <.05 for visit 2 compared with baseline).

Additional findings showed WHO FC improvements in 8 patients (53%; 95% CI, 27%- 79%). Further, pulmonary vascular resistance (from 9.2-5.7 Wood units) and mean pulmonary artery pressure (from 47.3-38.9 mm Hg) decreased significantly from baseline to visit 2 (P <.05). Cardiac index, in contrast, increased significantly from 2.3 L/min/m2 to 3.0 L/min/m2 from baseline to visit 2.

At baseline, 14 of the participants were at intermediate risk and 1 of the participants was at high risk. At visit 2, a total of 7 patients experienced a reduction in risk, 6 patients had a decrease in risk from intermediate to low, and 1 patient had a decrease in risk from high to low. In 8 patients, no change in risk was reported, with these individuals maintaining intermediate risk status. Some adverse effects were reported, but none were serious or unexpected. Overall, 3 patients died from unrelated causes and 1 patient underwent lung transplantation. The transplant-free survival rate was 85.1% at 36 months.

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This small study is the first of its kind to show that dual-treatment combinations other than ambrisentan plus tadalafil may be used in patients with PAH. The researchers concluded that additional research with a more definitive study design is warranted to further delineate the role of combined macitentan plus riociguat in patients with PAH.


Sulica R, Sangli S, Chakravarti A, Steiger D. Clinical and hemodynamic benefit of macitentan and riociguat upfront combination in patients with pulmonary arterial hypertension [published online January 14, 2019]. Pulm Circ. doi:10.1177/2045894019826944