Table 3: Overview of economic evaluation outcomes of included studies.

ReferencesComparisonEffectiveness/benefitsCosts (original currency; mean)Costs (2017 US$; mean)ICER (2017 US$ per QALY)Threshold of ICER (per QALY)Sensitivity or uncertainty analysis

Highland et al. [12](1) Bosentan vs. epoprostenolIncremental effectiveness: 11 QALYs per 100 patientsIncremental costs: $3631900 per 100 patients/yrIncremental costs: $4641721.88 per 100 patients/yrDominatingNASensitivity analyses: results robust.
(2) Bosentan vs. treprostinilIncremental effectiveness: 11 QALYs per 100 patientsIncremental costs: $4873800 per 100 patients/yrIncremental costs: $6228922.62 per 100 patients/yrDominatingNA

Garin et al. [13](1) Bosentan vs. epoprostenolIncremental effectiveness: 5.77 QALYs per 100 patientsIncremental costs: $408213 per 100 patients/yrIncremental costs: $452508.19 per 100 patients/yrDominatingNASensitivity analyses had minimal impact on these results.
(2) Bosentan vs. treprostinilIncremental effectiveness: 5.92 QALYs per 100 patientsIncremental costs: $434684 per 100 patients/yrIncremental costs: $481851.56 per 100 patients/yr$81393.84$50000
(3) Bosentan vs. iloprostIncremental effectiveness: 3.09 QALYs per 100 patientsIncremental costs: $3466486 per 100 patients/yrIncremental costs: $3842634.40 per 100 patients/yrDominatingNA
(4) Bosentan vs. SitaxentanIncremental effectiveness: 0.16 QALYs per 100 patientsIncremental costs: $474 per 100 patients/yrIncremental costs: $525.43 per 100 patients/yr$3283.94$50000
(5) Bosentan vs. ambrisentanIncremental effectiveness: 0 QALYs per 100 patientsIncremental costs: $0 per 100 patients/yrIncremental costs: $0 per 100 patients/yr$0NA
(6) Bosentan vs. sildenafilIncremental effectiveness: 0 QALYs per 100 patientsIncremental costs: $3153535 per 100 patients/yrIncremental costs: $3495725.08 per 100 patients/yrDominatedNA

Coyle et al. [14](1) Bosentan vs. ambrisentan 5mgPatients with FC II
Incremental effectiveness: −0.73 QALYs per person (treatment, 3.904 QALYs; comparator, 4.634 QALYs)
Patients with FC II
Incremental costs: Can$29095 per person (treatment, Can$406282; comparator, Can$377187)
Patients with FC II
Incremental costs: $24105.22 per person (treatment, $336604.81; comparator, $312499.59)
DominatedNAExtensive sensitivity analyses: results robust. Probabilistic sensitivity analysis: results robust.
Patients with FC III
Incremental effectiveness: −0.22 QALYs per person (treatment, 2.960 QALYs; comparator, 3.180 QALYs)
Patients with FC III
Incremental costs: Can$61406 per person (treatment, Can$412979; comparator, Can$351573)
Patients with FC III
Incremental costs: $50874.90 per person (treatment, $342153.27; comparator, $291278.38)
DominatedNA
(2) Bosentan vs. ambrisentan 10mgPatients with FC II
Incremental effectiveness: −0.313 QALYs per person (treatment, 3.904 QALYs; comparator, 4.217 QALYs)
Patients with FC II
incremental costs: Can$28759 per person (treatment, Can$406282 comparator, Can$377523)
Patients with FC III
Incremental costs: $23826.84 per person (treatment, $336604.81; comparator, $312777.96)
DominatedNA
Patients with FC III
Incremental effectiveness: −0.083 QALYs per person (treatment, 2.960 QALYs; comparator, 3.043 QALYs)
Patients with FC III
Incremental costs: Can$36095 per person (treatment, Can$412979; comparator, Can$376884)
Patients with FC III
Incremental costs: $29904.7 per person (treatment, $342153.27; comparator, $312248.55)
DominatedNA
(3) Bosentan vs. sildenafilPatients with FC II incremental effectiveness: −0.7593 QALYs per person (treatment, 3.904 QALYs; comparator, 4.663 QALYs)Patients with FC II incremental costs: Can$260028 per person (treatment, Can$406282 comparator, Can$146254)Patients with FC II incremental costs: $215433.31 per person (treatment, $336604.81; comparator, $121171.50)DominatedNA
Patients with FC III
Incremental effectiveness: −0.324 QALYs per person (treatment, 2.960 QALYs; comparator, 3.284 QALYs)
Patients with FC III
Incremental costs: Can$231860 per person (treatment, Can$412979; comparator, Can$181119)
Patients with FC III
Incremental costs: $192096.11 per person (treatment, $342153.27; comparator, $150057.17)
DominatedNA
(4) Bosentan vs. tadalafilPatients with FC II
Incremental effectiveness: −0.098 QALYs per person (treatment, 3.904 QALYs; comparator, 4.002 QALYs)
Patients with FC II
Incremental costs: Can$253037 per person (treatment, Can$406282 comparator, Can$153245)
Patients with FC II
Incremental costs: $209641.26 per person (treatment, $336604.81; comparator, $126963.55)
DominatedNA
Patients with FC III
Incremental effectiveness: −0.053 QALYs per person (treatment, 2.960 QALYs; comparator, 3.013 QALYs)
Patients with FC III
Incremental costs: Can$212395 per person (treatment, Can$412979; comparator, Can$200584)
Patients with FC III
Incremental costs: $175969.35 per person (treatment, $342153.27; comparator, $166183.93)
DominatedNA
(5) Bosentan vs. supportive carePatients with FC II
Incremental effectiveness: 0.686 QALYs per person (treatment, 3.904 QALYs; comparator, 3.128 QALYs)
Patients with FCII
Incremental costs: Can$251126 per person (treatment, Can$406282 comparator, Can$155156)
Patients with FCII
Incremental costs: $208058.00 per person (treatment, $336604.81; comparator, $128815.82)
$303291.55$165700.08 (Can$200000)
Patients with FC III
Incremental effectiveness: 0.273 QALYs per person (treatment, 2.960 QALYs; comparator, 2.687 QALYs)
Patients with FC III
Incremental costs: Can$208694 per person (treatment, Can$412979; comparator, Can$204285)
Patients with FC III
Incremental costs: $172903.07 per person (treatment, $342153.27; comparator, $169250.2)
$633344.58$165700.08 (Can$200000)

Dranitsaris et al. [15](1) Bosentan vs. ambrisentanNAIncremental costs: Can$16302 per patient (treatment, Can$164745; comparator, Can$148443)Incremental costs: $14956.40 per patient (treatment, $151146.60; comparator, $136190.20)NANAOne-way sensitivity analysis: results sensitive to sildenafil dose, ambrisentan daily drug cost, and bosentan daily drug cost.
(2) Bosentan vs. sitaxentanNAIncremental costs: Can$6307 per patient (treatment, Can$164745; comparator, Can$158444)Incremental costs: $5786.41 per patient (treatment, $151146.60; comparator, $145365.70)NANA
(3) Bosentan vs. sildenafilNAIncremental costs: Can$116394 per patient (treatment, Can$164745; comparator, Can$48351)Incremental costs: $106786.59 per patient (treatment, $151146.60; comparator, $44360.01)NANA
Wlodarczyk et al. [16]Bosentan vs. conventional careAt 5years incremental effectiveness: 1.39 life expectancyAt 5years incremental costs: A$116929 for each patientAt 5years incremental costs: $101787.70 for each patient$73228.56$41928.72 (A$60000)One-way sensitivity analysis: removing the PBS continuation rules from the model, halving of the annual mortality rate in patients treated with conventional therapy, and changing mortality and hospitalization RR affected the results.
At 10years incremental effectiveness: 2.93 life expectancyAt 10years incremental costs: A$181808 for each patientAt 10years incremental costs: $158265.43 for each patient$54015.51$41928.72 (A$60000)
At 15years incremental effectiveness: 3.87 life expectancyAt 15years incremental costs: A$216331 for each patientAt 15years incremental costs: $188318.00 for each patient$48660.98$41928.72 (A$60000)

Stevenson et al. [17]Bosentan vs. palliative therapyPatients with iPAH
Incremental effectiveness: 0.37 QALYs per patient (treatment, 3.32 QALYs; comparator, 2.95 QALYs)
Patients with iPAH
Incremental costs: £69000 per patient (treatment, £134000; comparator, £203000)
Patients with iPAH
Incremental costs: $111639.98 per patient (treatment, $216808.07; comparator, $328448.05)
DominatingNAThe results were similar in both the deterministic and probabilistic analyses.
Patients with PAH-CTD
Incremental effectiveness: 0.15 QALYs per patient (treatment, 1.36 QALYs; comparator, 1.21 QALYs)
Patients with PAH-CTD
Incremental costs: £32000 per patient (treatment, £62000; comparator, £94000)
Patients with PAH-CTD
Incremental costs: $51775.06 per patient (treatment, $100314.18; comparator, $152089.25)
DominatingNA

Fan et al. [18]Bosentan vs. palliative therapyIncremental effectiveness: 6.19 QALYs per person (treatment, 7.23 QALYs; comparator, 1.04 QALYs)Incremental costs: ¥439046.77 per patient (treatment, ¥504293.75; comparator, ¥65246.98)Incremental costs: $125227.26 per patient (treatment, $143837.35; comparator, $18610.09)$20230.58$39815.46 (¥139593)Sensitivity analyses: results robust.

Barbieri et al. [19]Bosentan vs. ambrisentanNAIncremental costs: €1112145 (treatment, €87594291; comparator, €86482146)Incremental costs: $1184990.49 (treatment, $93331717.06; comparator, $92146726.56)NANAThe sensitivity analysis corroborated the base case findings.

Note. “Dominating” denotes bosentan treatment producing more QALYs at a lower cost, whereas “dominated” denotes bosentan producing less QALYs at a higher cost. ICER: incremental cost-effectiveness ratio; QALY: quality-adjusted life-year; yr: year; PAH: pulmonary arterial hypertension; FC: functional class; NA: not applicable; CTD: connective tissue disease.