A meta‑analysis of the safety and efficacy of bosentan therapy combined with prostacyclin analogues or phosphodiesterase type‑5 inhibitors for pulmonary arterial hypertension

Figures

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  Figure 1.. Flow diagram for the studies included in the meta-analysis concerning the therapy effect of bosentan combined with either prostacyclin analogues or phosphodiesterase type 5 inhibitors in PAH. PAH, pulmonary arterial hypertension.

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  Figure 2.. Risk of bias summary. (A) Risk of bias for each included RCT, representing low risk of bias (+), high risk of bias (−), and unclear risk of bias (?). (B) Bar chart comparing percentage risk of bias for each included RCT. Green, low risk of bias high; red, risk of bias; yellow, unclear risk of bias. RCT, randomized controlled trial.

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  Figure 3.. Effect of bosentan combined with prostacyclin analogues or phosphodiesterase type 5 inhibitors vs. bosentan monotherapy on 6MWD. There was no significant heterogeneity (I2=0%; P=0.81) The mean difference of 6MWD was not significant between bosentan combination and bosentan monotherapy (P=0.13). 6MWD, six-minute walking distance; CI, confidence intervals; CT, combination therapy; IV, inverse variance; MT, monotherapy.

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  Figure 4.. Effect of bosentan combined with prostacyclin analogues or phosphodiesterase type 5 inhibitors vs. bosentan monotherapy on WHO functional class improvement. (A) WHO functional class improvement I and (B) WHO functional class improvement II. Functional class improvement I and II from baseline to endpoint of study were not significantly different in bosentan monotherapy and bosentan combination therapy (P>0.05). CI, confidence intervals; CT, combination therapy; M-H, Mantel-Haenszel; MT, monotherapy; WHO, World Health Organization.

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  Figure 5.. Effect of bosentan combined with prostacyclin analogues or phosphodiesterase type 5 inhibitors vs. bosentan monotherapy on mean pulmonary artery pressure. Compared with bosentan monotherapy, combination therapy may significantly reduce mPAP (P<0.05). CI, confidence intervals; CT, combination therapy; IV, inverse variance; MT, monotherapy; SD, standard deviation; mPAP, mean pulmonary artery pressure.

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  Figure 6.. Effect of bosentan combined with prostacyclin analogues or phosphodiesterase type 5 inhibitors vs. bosentan monotherapy on clinical worsening. The heterogeneity between the groups was found to be non-significant. Clinical worsening incidence in the combination therapy was below that of monotherapy, but without statistical significance (P>0.05). CI, confidence intervals; CT, combination therapy; M-H, Mantel-Haenszel; MT, monotherapy.

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  Figure 7.. Effect of bosentan combined with prostacyclin analogues or phosphodiesterase type 5 inhibitors vs. bosentan monotherapy on adverse events. The incidence of adverse events was not significantly different between the bosentan combination therapy and the monotherapy groups (P>0.05). CI, confidence intervals; CT, combination therapy; M-H, Mantel-Haenszel; MT, monotherapy.