• Hong-Da Zhang, Rui Zhang, Xin Jiang, Kai Sun, Dan-Chen Wu, and Zhi-Cheng Jing.
• Department of Cardio-Pulmonary Circulation, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China.
• Am. Heart J. 2015 Jul 1; 170 (1): 96-103, 103.e1-14.

BackgroundMany targeted therapies have been approved for pulmonary arterial hypertension (PAH), most of which are in oral forms. However, the effects of these drugs on lifesaving are unclear. Our objective was to evaluate the effects of oral treatments on clinical outcomes especially all-cause mortality in patients with PAH.MethodsMEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials were searched for relevant articles up to April 2014. Randomized, double-blind, parallel-group clinical trials that compared oral agents with placebo were selected. Data for populations, interventions, and outcomes were extracted independently by 2 investigators, and disagreements were resolved by consensus. Quality assessment was performed using the Cochrane risk-of-bias tool.ResultsTwenty-one randomized, controlled, clinical trials involving 5105 patients were identified in the primary analysis. The overall estimated odds ratio (OR) of combined clinical worsening (CCW) events between active treatment groups and control groups was 0.55 (95% CI 0.47-0.64, P < .001). However, the effect of oral treatments on reducing all-cause mortality was not statistically significant (OR 0.82, 95% CI 0.61-1.10, P = .192), which was consistent for approved drugs (OR 0.84, 95% CI 0.61-1.18, P = .316) and drugs that were not approved (OR 0.72, 95% CI 0.36-1.44, P = .352). In the sensitivity analysis, a significant reduction was achieved in CCW events (P < .001) but not in all-cause mortality (P = .057).ConclusionsThis pooled analysis shows the benefits of oral treatments on CCW events in patients with PAH. However, these drugs seem to exhibit less favorable effects on life expectancy in the short-term follow-up, suggesting further evaluation is required.Copyright © 2015 Elsevier Inc. All rights reserved.

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