Five randomised controlled trials (RCTs) were included in the review (n=190 participants). Three RCTs were cross-over design, while the other two were parallel group trials.
Sildenafil versus placebo: Patients in the sildenafil group showed significantly greater improvements in the six minutes walk test (weighted mean difference 68.90 metres, 95% confidence interval (CI): 31.14 to 106.65; three RCTs); mean pulmonary artery pressure (weighted mean difference -13.04 mmHg, 95% CI: -25.94 to -0.15; three RCTs); mean cardiac index (weighted mean difference 0.39 l/min/m2, 95% CI: 0.24 to 0.54; one RCT); mean Borg dyspnea score (weighted mean difference -1.23, 95% CI: -1.36 to -1.10; two RCTs); mean pulmonary vascular resistance (weighted mean difference -171 dyn.sec.cm-5, 95% CI: -300 to -30.90; one RCT) and improvement in functional class (odd ratio 6.48, 95% CI: 2.74 to 15.33; two RCTs). There were no significant differences between groups for mean right atrial pressure or number of patients with clinical worsening.
In the comparison of sildenafil with placebo for improvements in the six minutes walk test, publication bias could not be ruled out and 11 studies would be required to reverse the direction of study results according to Rosenthal's File Drawer Method.
Sildenafil versus bosentan: There were no significant differences between groups for the six minutes walk test, mean cardiac index or mean Borg dyspnea score.