Functional and haemodynamic changes in response to pulmonary arterial hypertension medications among adults with congenital heart disease
| Study (reference) Trial | Drug | Mean duration | Sample size* | % improvement in mean 6MWD | % improvement in mean PVR | % improvement in mean mPAP |
| Rosenkranz et al
1 PATENT-1 | (a) Riociguat 1.5 mg three times daily (b) Riociguat 2.5 mg three times daily (c) Placebo | 12 weeks | (a) 8 (b) 15 (c) 12 | (a) 11.00 (b) 10.57 (c) No significant improvement | (a) 12.03 (b) 22.12 (c) −5.03 | (a) 4.48 (b) 6.78 (c) No significant improvement |
| Rosenkranz et al
1 PATENT-2 (open-label extension to PATENT-1) | Riociguat 2.5 mg three times daily | 2 years (an additional 45 months following the end of PATENT-1) | (a) 6 patients who were originally in the riociguat 1.5 mg arm of PATENT-1 (b) 10 patients who were originally in the riociguat 2.5 mg arm of PATENT-1 (c) 9 patients who were originally in the placebo arm of PATENT-1 (d) 25 (total number of patients who completed PATENT-2) | (a) 13.55† (b) 29.27† (c) 9.44† (d) 18.34† | Not reported | Not reported |
| Ibrahim et al 11 | Bosentan | 16 weeks | 10 | 9.21 | Not reported | Not reported |
| Gatzoulis et al 12 | Bosentan | 3 months | 10 | 39.76 | Not reported | Not reported |
| D’Alto et al 13 | Bosentan | 1 year | 24 | 23.13 | 36.36 | Not reported |
| Benza et al 14 | Bosentan | 1 year | 24 | 10.37 | 23.98 | 13.33 |
| Kotlyar et al 15 | Bosentan | 15 months | (a) 17 treatment-naive patients (b) 6 patients already receiving PAH-specific therapy | (a) 8.49 (b) No significant improvement | Not reported | Not reported |
| Sitbon et al 16 | Bosentan | 18.3 months | 27 | 22.15 | 28.28 | No significant improvement |
| Schulze-Neick et al 17 | Bosentan | 2.1 years | 33 | 19.89 | No significant improvement | No significant improvement |
| Diller et al 18 | Bosentan | 2 years | 18 | 43.66 | Not reported | Not reported |
| Galiè et al
19 BREATHE-5 | (a) Bosentan (b) Placebo | 16 weeks | (a) 37 (b) 17 | (a) 12.08 (b) −2.74 | (a) 9.30 (b) −5.40 | (a) 7.07 (b) No significant improvement |
| Gatzoulis et al
20 Open-label extension to BREATHE-5 (19) | Bosentan | 40 weeks (an additional 24 weeks following the end of BREATHE-5) | (a) 26 patients who were originally in the bosentan arm of BREATHE-5 (b) 11 patients who were originally in the placebo arm of BREATHE-5 | (a) 14.20† (b) 8.30† | Not reported | Not reported |
| Apostolopoulou et al 21 | Bosentan | 16 weeks | 21 | 11.03 | 22.66 | 6.90 |
| Apostolopoulou et al
22 Extension to the 16-week-long study by Apostolopoulou21 | Bosentan | 2 years (an additional 44 months following the end of the initial 16-week-long study) | 19 | −3.73† | Not reported | Not reported |
| Van Loon et al 23 | Bosentan | (a) 1 year (b) 2.7 years | 20 | (a) 12.89 (b) 5.15† | Not reported | Not reported |
| Duffels et al 24 | Bosentan | (a) 6 months (b) 22 months | 58 | (a) 7.96 (b) 0† | Not reported | Not reported |
| Kermeen et al 25 | Bosentan or sitaxsentan | 1 year | 49 | 36.88 | Not reported | Not reported |
| D’Alto et al 26 | Bosentan | 13.6 months | (a) 19 patients with Down syndrome (b) 58 patients without Down syndrome | (a) 20.50 (b) 13.41 | (a) 25.00 (b) 23.10 | (a) 9.00 (b) 0 |
| Herbert et al 30 | Macitentan | 9.6 months (mean duration) | (a) 6 patients naive to bosentan (b) 9 patients previously treated with bosentan | (a) 58.85 (b) 7.71 | Not reported | Not reported |
| Blok et al 31 | Macitentan | 6 months | 40 | No significant improvement | Not reported | Not reported |
| Fernandes et al 32 | Epoprostenol | 3 months | 8 | 780.00 | 48.78 | Not reported |
| Rosenzweig et al 33 | Epoprostenol | 1 year | 20 | 12.75 | 52.00 | 20.78 |
| Galie et al
36 ALPHABET | (a) Beraprost (b) Placebo | 12 weeks | (a) 9 (b) 15 | (a) No significant improvement (b) No significant improvement | (a) No significant improvement (b) No significant improvement | (a) No significant improvement (b) No significant improvement |
| Chau et al 39 | Sildenafil | 6 weeks | 7 | No significant improvement | 43.08 | 25.71 |
| D’Alto et al 40 | Sildenafil | 6 months | 32 | 22.87 | 20.84% | No significant improvement |
| Zeng et al 41 | Sildenafil | 12 weeks | (a) 15 patients with ASD (b) 24 patients with VSD (c) 16 patients with PDA | (a) 15.65 (b) 11.32 (c) 14.58 | (a) 30.89 (b) 24.76 (c) 31.72 | (a) No significant improvement (b) 11.28 (c) No significant improvement |
| Mukhopadhyay et al 43 | Tadalafil | 12 weeks | 16 | 12.50 | 31.23 | 7.65 |
*Sample size may not reflect the total number of patients enrolled in each study as it only includes the number of adult patients with PAH-CHD (ie, this table excludes enrolled patients with other forms of PAH and it excludes all paediatric patients).
†Values reported reflect changes from baseline values.
6MWD, 6 min walking distance; ALPHABET, Arterial Pulmonary Hypertension and Beraprost European Trial; ASD, atrial septal defect; BREATHE-5, Bosentan Randomised Trial of Endothelin Antagonist THErapy-5; mPAP, mean pulmonary arterial pressure; PAH, pulmonary arterial hypertension; PAH-CHD, pulmonary arterial hypertension due to congenital heart disease; PATENT-1, Pulmonary Arterial hyperTENsion sGC-stimulator Trial-1; PATENT-2, Pulmonary Arterial hyperTENsion sGC-stimulator Trial-2; PDA patent ductus arteriosus; PVR, pulmonary vascular resistance; VSD, ventricular septal defect; WHO FC, WHO functional class.