Pulmonary vasodilator therapies in pulmonary arterial hypertension associated with CHD: a systematic review and network meta-analysis.

The optimal treatment strategy using pulmonary vasodilators in pulmonary arterial hypertension associated with CHD (PAH-CHD) remains controversial. We aimed to compare the efficacy and safety of pulmonary vasodilators in PAH-CHD. PubMed and EMBASE databases were searched through May 2022 and a network meta-analysis was conducted. The primary outcomes were mean difference of changes in 6-minute walk distance, NYHA functional class, and N-terminal pro-brain natriuretic peptide. The secondary outcomes included pulmonary vascular resistance, mean pulmonary arterial pressure, and resting oxygen saturation. We identified 14 studies, yielding 807 patients with PAH-CHD. Bosentan and sildenafil were associated with a significant increase in 6-minute walk distance from baseline compared with placebo (MD 48.92 m, 95% CI 0.32 to 97.55 and MD 59.70 m, 95% CI 0.88 to 118.53, respectively). Bosentan, sildenafil, and combination of bosentan and sildenafil were associated with significant improvement in NYHA functional class compared with placebo (MD -0.33, 95% CI -0.51 to -0.14, MD -0.58, 95% CI -0.75 to -0.22 and MD -0.62, 95% CI -0.92 to -0.31, respectively). Bosentan and sildenafil were also associated with significant improvements in secondary outcomes. These findings were largely confirmed in the subgroup analysis. Various adverse events were reported; however, serious adverse event rates were relatively low (4.8-8.7%), including right heart failure, acute kidney injury, respiratory failure, hypotension, and discontinuation of pulmonary vasodilators. In conclusion, bosentan and sildenafil were the most effective in improving prognostic risk factor such as 6-minute walk distance and NYHA class. Overall, pulmonary vasodilators were well tolerated in PAH-CHD.