01 March 2017 by Roxana Sulica

Clinical and hemodynamic benefit of macitentan and riociguat upfront combination in patients with PAH


Upfront combination therapy in PAH patients has become common practice.  We sought to evaluate the effect of initial macitentan and riociguat in combination.


We evaluated 14 consecutive PAH patients from 2014-2016 in our practice who received macitentan and riociguat upon the diagnosis of PAH.  We collected clinical (WHO functional class, 6-minute walk distance, BNP) at 3 and 12 months and hemodynamic data at 12 months.  Statistical analysis, included ANOVA, student t test, and chi-square tests as appropriate. 


There were 11/14 (78%) women and mean age for the group was 54 years.  Six patients had IPAH, and eight patients had APAH.  Six-minute walk distance increased from a mean of 304 m at baseline to 343 m at 3 months and was maintained at 338 m at 12 months, p<0.05 for the first follow-up compared to baseline. (Fig 1).  BNP decreased from 251 pg/mL at baseline to 123 pg/mL at 3 months and 93 pg/mL at 12 months, p<0.05 for the last follow-up compared to baseline. (Fig 2). There was an improvement in functional class in 57% of the patients, and no patient had functional class deterioration. (Fig 3).  Hemodynamic data is presented in Table 1. Riociguat uptitration was stopped in two patients due to hypotension and in one patient due to headache. By the end of the follow-up period, four patients required addition of a third drug, two patients received subcutaneous treprostinil, one patient inhaled treprostinil, and one patient oral selexipag.


Initial therapy with macitentan and riociguat in patients with PAH leads to clinical and hemodynamic benefit and is well tolerated. Careful follow-up is required to identify patients with progressive disease who require additional therapy.  Further investigations are required to delineate the role of this upfront combination in PAH.

Key Contributors

Roxana Sulica MD, Swathi Sangli MD, Aloke Chakravarti MD, David Steiger MD

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