Table 4. Clinical trials of combination therapy in pulmonary arterial hypertension (PAH)
Trial [ref.]Background therapy/study drugDesignPatientsSubjects nDuration weeksPrimary end-pointEfficacy
Primary end-pointTTCW
BREATHE-2 [30]Epoprostenol/bosentanUpfront RCTIPAH, SSc, SLE3316TPR-ND
STEP [31]Bosentan/iloprost (inhaled)Sequential RCTPAH67126MWD-+
COMBI [32]Bosentan/iloprost (inhaled)Sequential open labelIPAH40126MWD--
PACES [33]Epoprostenol/sildenafilSequential RCTIPAH, CTD, CHD277126MWD++
TRIUMPH-1 [34]Sildenafil, bosentan or both/treprostinil (inhaled)Sequential RCTPAH235126MWD+-
FREEDOM-C [35]Sildenafil, ERA or both/treprostinil (oral)Sequential RCTPAH354166MWD--
IMPRES [36]≥2 PAH-specific therapies/imatinibSequential RCTIPAH, HPAH, CTD, CHD202246MWD+-
PHIRST [37]Bosentan/tadalafilSequential RCTPAH216#166MWD-ND
EARLY [23]Sildenafil/bosentanSequential RCTPAH2824PVR+ND
  • TTCW: time to clinical worsening; ERA: endothelin receptor antagonist; RCT: randomised controlled trial; IPAH: idiopathic PAH; SSc: systemic sclerosis; SLE: systemic lupus erythematosis; CTD: connective tissue disease; CHD: congenital heart disease; HPAH: heritable PAH; TPR: total pulmonary resistance; 6MWD: 6-min walk distance; PVR: pulmonary vascular resistance; ND: not determined; +: met end-point; -: did not meet end-point. #: only patients included in the subgroup analysis of patients who were receiving concomitant bosentan at baseline were included; : only patients included in the subgroup analysis of patients who were receiving concomitant sildenafil at baseline were included.