Key result
Ambrisentan plus tadalafil significantly improved 6-minute walking distance by a mean difference of 79 meters compared to placebo, while vardenafil and iloprost plus bosentan showed the best overall balance of efficacy and safety.
Why the study?
Do targeted drugs or drug combinations improve 6-minute walking distance and other clinical/hemodynamic outcomes in patients with pulmonary arterial hypertension?
Meta-Analysis (n=10,230)
Do targeted drugs or drug combinations improve 6-minute walking distance and other clinical/hemodynamic outcomes in patients with pulmonary arterial hypertension?
Mean Difference: 79 (95% CI 15–140)
In a network meta-analysis of PAH therapies, vardenafil and the combination of iloprost plus bosentan demonstrated relatively better performance in both efficacy and safety, though therapeutic choices should remain individualized.
May guide PAH therapy selection toward vardenafil or iloprost-bosentan; extends network meta-analytic comparisons of efficacy-safety balance.
, soluble guanylate cyclase stimulator and selective non-prostanoid prostacyclin receptor agonist. To solve the contradictions existing in reported trials and provide a comprehensive guideline for clinical practice. PubMed, Embase, Cochrane library, and clinicaltrials.gov were searched. The basic information about the article, trial, arm, intervention, and the detailed data of outcome, including 6 minutes walking distance (6MWD) change, WHO functional class (FC) improvement, Borg dyspnea score (BDS) change, cardiac index (CI) change, mean pulmonary arterial pressure (mPAP) change, mean right arterial pressure (mRAP) change, pulmonary vascular resistance (PVR) change, clinical worsening, hospitalization, death, severe adverse events (SAEs), and withdrawal were extracted. The rank of treatments was estimated. 10,230 cases provided the firsthand comparison data about targeted drugs for treating PAH. For 6MWD, ambrisentan + tadalafil, vardenafil, and sildenafil + bosentan were better than others. Epoprostenol, macitentan, and sildenafil represented a greater WHO FC improvement. Vardenafil and treprostinil were better for BDS. So were bosentan + epoprostenol and bosentan alone for CI. Iloprost plus bosentan, bosentan + epoprostenol, and epoprostenol were better for mPAP. Iloprost plus bosentan, bosentan alone, and selexipag could reduce PVR. Sildenafil, epoprostenol, and vardenafil had the highest probability to reduce the incidence of death and withdrawal. To conclude, vardenafil and iloprost + bosentan showed relatively better performance in both efficacy and safety. However, the therapeutic choice should be made according to both the feature of each therapy and the individual condition.
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Wang et al. (2018) conducted a meta-analysis in Pulmonary arterial hypertension (PAH) (n=10,230). Targeted drugs or drug combinations (e.g., ambrisentan + tadalafil, vardenafil, iloprost + bosentan) vs. Placebo or other targeted therapies was evaluated on 6 minutes walking distance (6MWD) change (MD 79, 95% CI 15-140). Ambrisentan plus tadalafil significantly improved 6-minute walking distance by a mean difference of 79 meters compared to placebo, while vardenafil and iloprost plus bosentan showed the best overall balance of efficacy and safety.
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