A Bayesian Network Meta-analysis of Add-on Drug Therapies Specific for Pulmonary Arterial Hypertension

Published on 2019-11-20T01:07:02Z (GMT) by
<div><p><b>Background:</b> Recently published meta-analyses did not discriminate between drug agents used for initial and sequential combination therapy. <b>Objective:</b> To assess the comparative efficacy of drugs specific for the treatment of pulmonary arterial hypertension (PAH) as add-on therapies based on 6-minute walk distance (6MWD), all-cause mortality, and discontinuation due to adverse events (AEs). <b>Methods:</b> EMBASE, PubMed, Cochrane Library, and <a href="https://ClinicalTrials.gov" target="_blank">ClinicalTrials.gov</a> were searched until December 9, 2018, for the randomized, placebo-controlled clinical trials (RCTs) conducted on primarily adult patients diagnosed with PAH. Data extracted from applicable RCTs were as follows: for 6MWD mean change from baseline, the total number of patients, and the number of patients with events, per treatment. Network meta-analysis (NMA) was conducted in a Bayesian framework. <b>Results:</b> A total of 16 RCTs were eligible for analysis, with 4112 patients. Add-on therapy with tadalafil or inhaled treprostinil performed better than endothelin receptor antagonists alone [27 m; 95% credible interval (CrI): (11, 43); and 19 m; 95% CrI: (10, 27); respectively]. Add-on therapy with macitentan or bosentan performed better than phosphodiesterase type 5 inhibitors alone [26 m; 95% CrI: (6.4, 45); and 22 m; 95% CrI: (5.1, 38); respectively]. Differences in all-cause mortality and discontinuation due to AEs were nonsignificant. <b>Conclusion and Relevance:</b> Our NMA evaluated efficacy and safety of add-on therapies in patients with PAH. None of the previous meta-analyses evaluated RCTs focusing solely on patients pretreated with another PAH-specific drug therapy. Our results support guideline recommendations on combination therapy in PAH patients and add the quantitative perspective on which sequential therapy demonstrated the greatest effect size.</p></div>

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Petrovič, Maja; Locatelli, Igor (2019): A Bayesian Network Meta-analysis of Add-on Drug Therapies Specific for Pulmonary Arterial Hypertension. SAGE Journals. Collection. https://doi.org/10.25384/SAGE.c.4745531.v1