Pulmonary artery hypertension (PAH) is an uncommon condition that worsens with time and is difficult to cure. In previous trials, active pharmacological treatments were found to enhance hemodynamics, surrogate outcomes, and mortality when compared to placebo. There are few direct trials of active therapies, thus comparisons of direct and indirect treatment effects can be made using a mixed treatment comparison network meta-analysis. The Oxford score was used to randomized controlled studies of patients with idiopathic or secondary PAH treated with epoprostenol, treprostinil, iloprost, beraprost, bosentan, ambrisentan, macitentan, sildenafil, tadalafil, vardenafil, or riociguat monotherapy. Data on 6-minute walk distance, cardiac index, pulmonary artery pressure, pulmonary vascular resistance, clinical deterioration, and mortality, as well as safety endpoints, were abstracted by reviewers. To create network geometry and assess treatments, a Bayesian mixed treatment comparison network meta-analysis employing Markov chain Monte Carlo analysis was performed. Twenty trials satisfied the requirements and were included in the analysis, resulting in a star-shaped evidence network with moderate variety and low co-occurrence.
There were 4,328 patients with idiopathic hypertension in World Health Organization functional class II (34%) or III (60%) PAH, with an average age of 51. Every treatment arm experienced significant disease progression, and no single treatment consistently outperformed placebo (direct comparisons) or any other active treatment (indirect comparisons) in terms of 6-minute walk distance, cardiac index, pulmonary artery pressure, pulmonary vascular resistance, clinical worsening, death, or any other safety endpoint.
For each objective, no therapy was clearly superior above placebo, either directly or indirectly. PAH therapy should be chosen based on individual treatment results, preferences, and tolerability.
Reference:journals.lww.com/clinpulm/Abstract/2017/07000/A_Mixed_Treatment_Comparison_Meta_Analysis_of.2.aspx
