Trials of treatment of portopulmonary hypertension
| Portopulmonary Hypertension Treatment WIth Macitentan—a Randomized Clinical Trial (PORTICO)27 |
| Design: Multicenter, randomized, double-blind, placebo-controlled trial of macitentan 10 mg by mouth once daily (n = 43) vs placebo (n = 42) for 12 weeks. |
| Inclusion and exclusion criteria: Adults age ≥ 18 with portopulmonary hypertension, 6-minute walking distance ≥ 50 m, pulmonary vascular resistance > 320 dynes·sec·cm−5; excluded patients with Model for End-stage Liver Disease score ≥ 19 or Child-Pugh class C liver disease. |
| Results: 35% reduction in pulmonary vascular resistance in macitentan group compared with placebo. |
| Comments: No hepatic safety concerns; more adverse effects (such as peripheral edema) in the macitentan group. |
| Subgroup analysis from Pulmonary Arterial Hypertension Soluble Guanylate Cyclase–Stimulator Trial 1 (PATENT-1) and PATENT-233–35 |
| Design: Multicenter, randomized, double-blind, placebo-controlled trial of riociguat up to 2.5 mg 3 times daily vs placebo for 12 weeks in 443 patients with pulmonary arterial hypertension (PATENT-1), of whom 13 had portopulmonary hypertension, with open-label extension in 396 patients who had no side effects (PATENT-2). |
| Inclusion criteria. Adults age ≥ 18, pulmonary arterial hypertension due to any cause, never treated or treated with endothelin receptor antagonist or prostacyclin analogue (except intravenous). |
| Results: Improvement in 6-minute walking distance (+ 48 meters with riociguat compared with +3 meters with placebo) Secondary end point: Improvement in World Health Organization functional class |
| Sustained effect noted at the end of 2 years in PATENT-2. |
| Comments: No hepatic safety concerns, but dose adjustment needed; peripheral edema and headache were common adverse effects. |
| Open-label trial of ambrisentan36 |
| Design: Open-label comparison of ambrisentan 5 mg once daily (titrated up to 10 mg once daily at or after week 4 if tolerated) for 24 weeks (n = 23), followed by long-term extension for 24–28 weeks (n = 19). |
| Inclusion criteria: Adults age ≥ 18 with portopulmonary hypertension, Child-Pugh class A or B, alanine aminotransferase and aspartate aminotransferase levels less than 5 times the upper limit of normal. |
| Results: No change in 6-minute walking distance, improvement in pulmonary vascular resistance (7.1 ± 5 vs 3.8 ± 1.8 WU, P < .001). Secondary end points: improvement in World Health Organization functional class, right atrial pressure, mean pulmonary artery pressure, and cardiac index. |
| Comments: Peripheral edema and headaches were common side effects. |