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Combination Therapy May Aid Right Ventricular Function in Patients With Severe PAH

Individuals with severe nonreversible pulmonary arterial hypertension (PAH) who receive triple upfront combination therapy with ambrisentan, tadalafil, and subcutaneous treprostinil may experience considerable clinical and hemodynamic improvement as well as right-sided heart reverse remodeling, according to a new study.

To evaluate the effects of triple upfront combination therapy on right ventricular (RV) function, the researchers analyzed outcomes among 21 patients (aged 44 ± 15 years) with newly diagnosed high-risk idiopathic PAH who had received upfront combination treatment of ambrisentan, tadalafil, and subcutaneous treprostinil. The patients’ PAH had to have been nonreversible by the inhalation of nitric oxide, and they had to have received the combination treatment between 2014 and 2018.

At baseline and again at follow-up, data on clinical evaluation, World Health Organization (WHO) functional class, 6-minute walk distance, biomarkers, echocardiography, and right-sided heart catheterization were recorded.

From baseline to the median 2-year follow-up, the following changes were observed:

  • The Registry to Evaluate Early and Long-term Pulmonary Arterial Hypertension Disease Management score decreased from 10 ± 1 to 5 ± 1
  • Right-sided atrial pressure decreased from 13 ± 3 mm Hg to 5 ± 2 mm Hg
  • Mean pulmonary artery pressure decreased from 60 ± 9 mm Hg to 42 ± 5 mm Hg
  • Pulmonary vascular resistance (PVR) decreased from 16.4 ± 4.4 Wood units to 5.5 ± 1.3 Wood units
  • N-terminal pro-brain natriuretic peptide decreased from 3379 ± 1921 pg/mL to 498 ± 223 pg/mL
  • WHO functional class decreased from 3.4 ± 0.5 to 2.0 ± 0.4 
  • Cardiac index increased from 1.8 ± 0.3 L/min/m2 to 3.5 ± 0.8 L/min/m2 
  • 6-minute walk distance increased from 158 ± 130 m to 431 ± 66 m 

 

Furthermore, echocardiography showed decreased right-sided atrial and RV areas, improved left ventricular eccentricity index, and increased fractional area change in proportion to treatment-induced decrease in PVR.

—Colleen Murphy

Reference:

D’Alto M, Badagliacca R, Argiento P, et al. Risk reduction and right heart reverse remodeling by upfront triple combination therapy in pulmonary arterial hypertension. CHEST. 2020;157(2):376-383. https://doi.org/10.1016/j.chest.2019.09.009.