A Bayesian Network Meta-analysis of Add-on Drug Therapies Specific for Pulmonary Arterial Hypertension
Abstract
Background: Recently published meta-analyses did not discriminate between drug agents used for initial and sequential combination therapy. Objective: 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). Methods: EMBASE, PubMed, Cochrane Library, and ClinicalTrials.gov 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. Results: 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. Conclusion and Relevance: Our NMA evaluated efficacy and safety of add-on therapies in patients…
How strong is the evidence?
Evidence Hub reads this as a meta-analysis, done in people. Its evidence level is 1 of 5 (Highest · pooled evidence). Pooled evidence from several studies sits at the top of the evidence pyramid. Reported size: 4,112 participants or records.
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