Introduction

Macitentan, is a highly potent, tissue-specific endothelin-receptor antagonist (ERA). The 2015 ESC/ERS guidelines recommend macitentan as a monotherapy or in combination for PAH patients in WHO-FC II and III. These guidelines established a 1-year mortality risk assessment, categorizing the patients as low, moderate or high risk on the basis of clinical criteria, activity and cardiac imaging. However, the validity of most of the criteria during follow-up of patients is not known. Parameters such as age, sex or etiology of PAH were not taken into consideration.

Aim

This study evaluates the clinical and echocardiographic progression in Indian patients with PAH treated with macitentan

Method

Study Design

• Retrospective observational cohort study

  Inclusion criteria

• PAH patients in the World Health Organization functional class (WHO-FC) II-IV treated with macitentan in routine clinical setting

Treatment Strategy

• PAH patients treated with macitentan were included in this study
• WHO-FC, 6-min walking distance, N-terminal prohormone of brain natriuretic peptide level (NT-pro-BNP), and echocardiographic data such as tricuspid annular plane systolic excursion (TAPSE), systolic pulmonary artery pressure (sPAP), and the occurrence of pericardial effusion were collected at baseline and 12-month follow-up
• The baseline and 12-month clinical variables were classified into low-, medium- and high-risk groups as per ESC/ERS guidelines on risk assessment

Endpoints

Improvements in

• WHO-FC
• 6-MWD
• NT-pro-BNP
• TAPSE
• sPAP
• Adverse events (AEs)

Results

• The study included 20 PAH patients treated with macitentan for 12 months; out of which 70% were women
• Baseline cohort characteristics were as follows
  • 50% were in WHO FC II, 35% were in FC III and 15% were in FC IV
  • Mean age was 43.4 years
  • 40% of the patients were treatment-naïve and macitentan was the first ERA
• Significant improvement in their FC was demonstrated by 85% of patients after 6 months of macitentan therapy
• Mean FC improved from 2.65+0.75 to 1.45+0.51; p<0.0001
• Mean 6-MWD improved from 331.65+105.88 m to 436.65+125.25 m; p<0.0001
• Substantial reduction in plasma levels of NT-pro BNP was noted; from 549.74 pg/l to 205.45 pg/l; p<0.0001
• An improvement in echocardiographic parameters was also observed; p<0.0001; TAPSE improved from 1.95 mm to 2.1mm and sPAP reduced from 80.5 mm Hg to 49.9 mm Hg
• Pericardial effusion found in 30% of the patients at baseline was not present after 12 months
• Only 2 patients reported minor AEs such as nasal congestion and nausea and other cases had mild elevation of liver enzymes

Conclusion

• Treatment with macitentan for 12 months resulted in significant improvements in clinical and echocardiographic parameters in Indian patients with multiple pulmonary arterial hypertension subclasses
• Macitentan was safe and well tolerated by all the patients

Lung India. 2022 Jan-Feb;39(1):12-15.