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

Abstract

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 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.

A Network Meta-analysis of the Efficacy and Safety of Targeted Drug Combinations in the Treatment of Pulmonary Arterial Hypertension

“…The results of previous meta-analysis showed that sildenafil combined with bosentan for PAH was effective in reducing mPAP, increasing 6MWD, reducing Borg dyspnea score, and improving WHO functional class, which is consistent with the results of this study. [48] However, when selecting the combination of bosentan and sildenafil, the drug-drug interactions should also be considered. Studies have shown that prolonged co-administration of bosentan and sildenafil results in lower plasma concentrations of sildenafil, and that the combination of sildenafil with P450 isoenzyme inducers such as bosentan results in increased clearance and a weaker therapeutic effect.…”

Secundum Atrial Septal Defect With Early Presentation of Eisenmenger Syndrome and Right-Heart Failure: A Rare Case Report and Literature Review

“…The conservative management focuses on monotherapy including endothelin receptor antagonists, phosphodiesterase-5 inhibitors, and prostanoids. In a meta-analysis of eight studies, it was shown that bosentan and phosphodiesterase-5 inhibitors improved exercise tolerance and reduced vascular remodeling in patients, at the cost of a few adverse effects [16].…”