Figures
- Figure 1.
Established and putative mediators and pathways involved in the pathogenesis of pulmonary arterial hypertension. BMPR2: bone morphogenetic peptide receptor 2; VIP: vasoactive intestinal peptide; NO: nitric oxide; RANTES: regulated on activation, normal T-cell expressed and secreted; MCP: monocyte chemoattractant protein; IL: interleukin; PDGF: platelet-derived growth factor; EGF: epidermal growth factor; FGF: fibroblast growth factor; VEGF: vascular epidermal growth factor; PDK: pyruvate dehydrogenase kinase; PDH: pyruvate dehydrogenase.
- Figure 2.
Compounds acting on pathogenic pathways of pulmonary arterial hypertension. BMPR2: bone morphogenetic peptide receptor 2; VIP: vasoactive intestinal peptide; NO: nitric oxide; RANTES: regulated on activation, normal T-cell expressed and secreted; MCP: monocyte chemoattractant protein; IL: interleukin; PDGF: platelet-derived growth factor; EGF: epidermal growth factor; FGF: fibroblast growth factor; VEGF: vascular epidermal growth factor; PDK: pyruvate dehydrogenase kinase; PDH: pyruvate dehydrogenase; eNOS: endothelial nitric oxide synthase; BH4: tetrahydrobiopterin; ACE: angiotensin-converting enzyme; CCB: calcium channel blocker; HDAC: histone deacetylase; NFATc: nuclear factor of activated T-cells, cytoplasmic; PLC: phospholipase C; BMP: bone morphogenetic peptide; PPAR: peroxisome proliferator-activated receptor; NO2-FA: nitrated fatty acid; IP: prostaglandin receptor; ERA: endothelin receptor antagonist; PDE5-i: phosphodiesterase type-5 inhibitor.
- Figure 3.
Change in pulmonary vascular resistance (PVR) from baseline to week 17 (per protocol analysis). Data are presented as geometric means and error bars represent 95% confidence limits (CL). Baseline PVR values (mean±sd) for per protocol population for selexipag were 951.9±434.5 dyn·s·cm−5 and for placebo were 826.8±195.8 dyn·s·cm−5. TE: treatment effect. Reproduced from [31].
Tables
- Table 1. Efficacy parameters tested in historical registration trials of drugs approved for use in pulmonary arterial hypertension
Drug Study acronym Parameters that improved [Ref.] Exercise capacity FC Haemodynamics TTCW Signs and symptoms Survival Endothelin pathway Bosentan Study 351 BREATHE-1 ↑ ↑ ↑ ↑ ↑ NT [4, 5] Sitaxsentan# STRIDE-1 and 2 ↑ ↑ ↑ ↓ ↓ NT [6, 7] Ambrisentan ARIES-1 and 2 ↑ ↑ ↑ ↑ ↑ NT [8] NO pathway Sildenafil SUPER-1 ↑ ↑ ↑ ↓ ↓ NT [9] Tadalafil PHIRST ↑ ↓ ↑ ↑ ↓ NT [10] Prostacyclin pathway Intravenous epoprostenol ↑ ↑ ↑ NT NT ↑ [11, 12] Inhaled iloprost AIR ↑ ↑ ↑ ↑¶ ↑ NT [13] Subcutaneous treprostinil ↑ NT ↑ ↑ ↑ NT [14] Inhaled treprostinil TRIUMPH ↑ ↓ NT ↓ ↓ NT [15] Oral beraprost ALPHABET ↑ ↑ ↓ ↑ ↑ NT [16, 17] FC: functional class; TTCW: time to clinical worsening; NO: nitric oxide; NT: not tested; ↑: parameter improved; ↓: parameter did not improve. #: withdrawn from market in 2010 due to two cases of fatal hepatic failure linked to its use; ¶: TTCW was defined as a combination of ≥10% improvement in walking distance combined with an absence of clinical deterioration.
Disclosures
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