Table 1.
Characteristics of the trials included in the meta-analysis.
| Studies | Study design | Drug | Sample size | Patient age | Outcomes | Conclusions |
|---|---|---|---|---|---|---|
| Giardini A, 2008 | RCT | Sildenafil (0.7 mg/kg, range 25–50 mg) | 55 | 22.8 ± 4.9 (16–32) | Peak VO2 | Sildenafil improves exercise capacity and increases PBF and CI |
| Goldberg DJ, 2011 | RCT | Sildenafil (20 mg 3 × daily) | 55 | 14.9 ± 5.1 | Peak VO2 | Sildenafil did not cause an improvement in VO2 max; but there was an increase in ventilatory efficiency and a suggestion of improved oxygen consumption in two subgroups |
| Giordano R, 2015 | Retrospective RCT | Sildenafil (0.35 mg/kg × 4 h) | 30 | >18 years | Mortality, mPAP | Sildenafil may be used in postoperative Fontan operations, with positive effectiveness |
| Mendoza A, 2015 | Prospective RCT | Sildenafil and nitric oxide (4.6 ± 1.6 mg/kg/day) | 48 | 5.4 ± 1.7(man) 5.7 ± 2.7 (woman) | Mortality | Postoperative administration of sildenafil and nitric oxide had no influence on early postoperative outcomes after the modified Fontan procedure, in terms of duration of pleural effusions, mechanical ventilation time, length of stay in the ICU, and length of hospital stay |
| Mark JS, 2013 | RCT | Bosentan (125 mg 2 × daily) | 48 | 28 (18–55) | NYHA class, peak VO2, BNP | An increased NT-proBNP level was present in the majority of Fontan patients. Six months of bosentan treatment was not beneficial |
| Shang SK, 2013 | RCT | Bosentan (≤10 kg: 7.8125 mg 2× daily; 10–20 kg: 15.625 mg 2× daily; 20–30 kg: 31.25 mg 2× daily; >30 kg: 62.5 mg 2× daily) | 39 | 2.5–18 | Mortality, NYHA class. 6MWD, BNP, | Bosentan reduces the incidence of pulmonary arteriovenous fistulae and protein-losing enteropathy and improve heart function |
| Hebert A, 2014 | RCT | Bosentan (62.5 mg 2× daily for 2 weeks; 125 mg 2× daily for 12 weeks) | 69 | 20 ± 7.4 | NYHA class, Peak VO2, BNP | Bosentan improves exercise capacity and time, as well as NYHA functional class, without serious adverse effects |
| Cedars AM, 2016 | RCT | Ambrisentan (5 mg × daily) | 28 | >18 years | Peak VO2 | Ambrisentan improves exercise capacity in adult Fontan patients |
| Shang SK, 2016 | RCT | Bosentan (≤10 kg: 7.8125 mg, ×2 daily; 10–20 kg: 15.625 mg × 2 daily; 20–30 kg: 31.25 mg × 2 daily; >30 kg: 62.5 mg × 2 daily) | 9 | 11.13 ± 4.13 (6.5–16) | Mortality, mPAP, NYHA class, 6MWD | Bosentan improves NYHA functional status and improves the results of the 6-min walking test (6MWT) in Fontan patients post-surgery, and no other benefits were observed |
BNP: brain natriuretic peptide; mPAP: mean pulmonary artery pressure; NYHA: New York Heart Association; peak VO2: peak oxygen uptake; RCT: randomized controlled trials; 6MWD: six-minute walking distance.