Table 4

Characteristics of RCTs with PAH drugs interfering with the nitric oxide pathway (soluble guanylate cyclase stimulators, phosphodiesterase type-5 inhibitors)

Drug(s) testedStudyPatients numberDuration (weeks)Background TherapyPrimary end pointMain results
RiociguatPATENT4544312No or
bosentan or prostanoids
6MWD6MWD improved
Haemodynamics improved
PATENT plus473018SildenafilSupine SBPTerminated for excess of SAE in the treated group
SildenafilSUPER-14827712No6MWD6MWD improved
TTCW not improved
Sastry492212NoTTTT improved
Singh50206No6MWD6MWD improved
PACES5126416Epoprostenol6MWD6MWD improved
TTCW and haemodynamics improved
Iversen522012bosentan6MWD6MWD not improved
Pfizer study
10312bosentan6MWD6MWD not improved
Sildenafil (paediatric)STARTS-13923516NoTT%change in VO2 max, functional class and hemodynamic improved with medium and high doses
STARTS-240206208NoSurvivalSurvival improved
TadalafilPHIRST5340516No or
bosentan (54%)
6MWD6MWD improved (in bosentan treated patients +23 m, 95% CI –2 to 48 m) TTCW improved
Vardenafil*EVALUATION546612No6MWD6MWD improved
TTCW improved
  • Modified from Galiè N et al.12

  • Note that most of the listed RCT data were derived from studies in adults with PAH. Healthcare providers must obtain valid information on the approval of any of the listed medications for use in paediatric PAH in the according country.

  • *This drug is not approved by the EMA for use in adult PAH at the time of submission of this manuscript.

  • 6MWD, 6 min walk distance; EMA, European Medicines Agency; PAH, pulmonary arterial hypertension; RCT, randomised controlled trial; TTCW, time to clinical worsening; TT, treadmill test.