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

Bosentan is an effective drug for the treatment of pulmonary arterial hypertension (PAH). The aim of the present meta-analysis was to examine the evidence concerning the efficacy and safety of bosentan therapy combined with prostacyclin analogues or phosphodiesterase type 5 (PDE-5) inhibitors for treating PAH. Eligible published studies were collected from Embase, PubMed, The Cochrane Library and the www.clinicaltrials.gov website. Heterogeneity was assessed using the Cochran Q-statistic test. Results were presented as risk ratios or mean differences with 95% confidence intervals (CI). A total of five studies, comprising 310 patients were included for analysis. No significant improvements in six-minute walk distance (6MWD; mean difference, 16.43 m), clinical worsening (risk ratio, 0.54) and the World Health Organization functional classification (class I: risk ratio, 1.17; class II: risk ratio, 1.18) were observed in patients treated with bosentan in combination with prostacyclin analogues or PDE-5 inhibitors. However, a significant reduction in the mean pulmonary artery pressure (mPAP; 95% CI: -17.06, -6.83; P<0.0001) following bosentan combination therapy was observed. Comparisons of adverse event rates in the bosentan combination therapy (55.6%) and monotherapy (51.8%) suggested that there is no reduction in adverse events (risk ratio, 1.10). The results indicated that bosentan combined with prostacyclin analogues or PDE-5 inhibitors may not improve 6MWD, cardiac function, clinical worsening and adverse events. However, bosentan combined with prostacyclin analogues or PDE-5 inhibitor therapy was able to significantly reduce mPAP compared with the effect of bosentan monotherapy.