Sildenafil for pulmonary hypertension: need for evidence generation

BACKGROUND: The present meta-analysis was conducted with the aim of comparing the usefulness of sildenafil for the management of pulmonary hypertension (PH). METHODS: A systematic electronic and manual search was conducted to retrieve all published and unpublished randomized clinical trials of sildenafil in PH. Pertinent data related to various outcomes were extracted. Sildenafil was planned for comparison with placebo, prostacyclin analogs and endothelin receptor antagonists. For continuous data weighted mean difference was used while fixed or random effects models were used for dichotomous data. Revman (Version 4.2) was used for all calculations. RESULTS: Five studies with a total of 190 patients were included in the final analysis. As compared to placebo sildenafil showed a significant improvement in 6-min walk test (68.90 (95% CI 31.14 - 106.65), p = 0.0003), mean pulmonary artery pressure (-13.04 (95% CI - 25.94 to -0.15), p = 0.05), mean cardiac index (0.39 (95% CI 0.24 - 0.54), p < 0.00001), mean Borg dyspnea score (-1.23 (95% CI -1.36 to -1.10), p < 0.00001), mean pulmonary vascular resistance (-171 (95% CI -300 to -30.90), p = 0.02), improvement in functional class (6.48 (95% CI 2.74 - 15.33), p < 0.001) and a nonsignificant change in mean right atrial pressure and clinical worsening. No study satisfied inclusion criteria for comparison with prostacyclin analogs. In comparison with bosentan, sildenafil did not show a significant difference for any of the clinical outcomes of concern. CONCLUSION: In conclusion, sildenafil was shown to produce a significant improvement in functional and clinical outcomes as compared to placebo. There was no significant difference between sildenafil and bosentan for the study outcomes. There is a definite need for conducting adequately powered randomized controlled trials of sildenafil comparing it to placebo and also to other treatments approved for use in PH.