Comparison between the efficacy of combination therapy and monotherapy in connective tissue disease associated pulmonary arterial hypertension: a systematic review and meta-analysis.

OBJECTIVES: Although the efficacy of combined treatment targeting pulmonary arterial hypertension (PAH) has been suggested to be preferable, the comparative efficacy of combination therapy versus monotherapy in connective tissue disease (CTD)-associated PAH (CTD-PAH) remains undetermined. We performed a meta-analysis regarding this topic. METHODS: The Cochrane Library, MEDLINE, PubMed, and EMBASE databases were searched for randomised controlled trials (RCTs) that directly compared the efficacies of combination therapy and monotherapy targeting PAH in patients with CTD-PAH. The risk of the clinical worsening of PAH and changes in 6-minute walk distance (6MWD) were evaluated. The Mantel-Hansel method was used to pool the results with a random-effects model. RESULTS: Six RCTs with 963 patients were included. The results of the meta-analysis showed that combination therapy significantly reduced the risk of clinical worsening events by 27% (pooled relative risk of 0.73, 95% confidence interval (CI) [0.60-0.89], p=0.002) with no significant heterogeneity (I2=13%, Ph=0.33) and tended to increase 6MWD by 21.38 m (95% CI [-20.38 to 63.14]; p=0.32; I2=58, Ph=0.09). No significant heterogeneity was indicated with funnel plots. CONCLUSIONS: Combination therapy targeting PAH may confer preferable therapeutic efficacy compared with monotherapy in patients with CTD-PAH as evidenced by a more remarkable reduction in the risk of clinical worsening and a probable improvement of exercise capacity in these patients.