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Ambrisentan and Tadalafil Synergistically Relax Endothelin-Induced Contraction of Rat Pulmonary Arteries

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Conference: 2014 International PHA Conference and Scientific Sessions

Release Date: 06.22.2014

Presentation Type: Abstracts

File Download: 2014 Conference Abstract - Liang

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Background: The question of which drug should be preferred for the treatment of pulmonary arterial hypertension (PAH) is unclear, and conventional meta-analyses cannot provide a hierarchy based on the randomised controlled trials. We aimed to integrate the available evidence to create hierarchies of the comparative efficacy and risk of all-cause discontinuation of PAH drugs.

Methods: We did a systematic review and network meta-analysis (which uses both direct and indirect comparisons) of randomised controlled trials to compare 13 drugs and placebo in the treatment of PAH. We searched MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials (CENTRAL) to identify relevant studies published from inception to October, 2013. Randomised controlled trials of patients with PAH were eligible. Data for interested outcomes were independently extracted by two reviewers. The primary outcome was efficacy and tolerability, as measured by 6-min walk test (6MWT) and all-cause discontinuation, respectively. We also examined WHO/NYHA function class, time to clinical worsening and hemodynamic parameters included mean pulmonary arterial pressure (MPAP) and mean right arterial pressure (MRAP).

Results: We identified 29 suitable studies, with data for 5412 participants. For efficacy, direct comparison showed that every drug except epoprostenol was better than placebo and vardenafil was better than others (Mean difference (MD) 69.00; 95%CI 40.08, 97.92) among different active drugs; network meta-analysis showed that ambrisentan, bosentan, iloprost, riociguat, sildenafil, sitaxsentan and vardenafil were superior to placebo and vardenafil was significantly more efficacious than beraprost, bosentan, macitentan, sitaxsentan and tadalafil. Besides, vardenafil might be the best in efficacy for PAH. For tolerability, vardenafil had the best tolerability than other drugs and placebo (Odds ratio (OR) 0.06; 95%CI 0.01, 0.56) from direct comparison, network meta-analysis showed that vardenafil were significantly better than other drugs apart from ambrisentan, epoprostenol, iloprost. Similarly, vardenafil might be the best in tolerability for PAH.

Conclusion: Our analysis suggested that vardenafil was better than other PAH drugs in terms of efficacy and tolerability, and could be used as a standard comparator in phase III and also in pragmatic (or effectiveness) trials to increase the real-world applicability of the results.