Targeted drugs for pulmonary arterial hypertension: a network meta-analysis of 32 randomized clinical trials

• Published in: Patient preference and adherence 2017-01, Vol.11, p.871-885
• Main Authors: Gao, Xiao-Fei, Zhang, Jun-Jie, Jiang, Xiao-Min, Ge, Zhen, Wang, Zhi-Mei, Li, Bing, Mao, Wen-Xing, Chen, Shao-Liang
• Format: Article
• Language: English
• Subjects: 6-minute walk distance; Ambrisentan; Antihypertensive agents; Bosentan; Comparative analysis; Complications and side effects; Diseases; Dosage and administration; Drug therapy; Drugs; Endothelin; Epoprostenol; Heart failure; Hypertension; Iloprost; Macitentan; Mortality; network meta-analysis; Original Research; Patient outcomes; Platelet aggregation inhibitors; Product development; prostanoids; Pulmonary arterial hypertension; Pulmonary hypertension; Riociguat; Sitaxsentan; targeted drugs; Treprostinil; Vardenafil; Vasodilator agents
• ISSN: 1177-889X; 1177-889X
• DOI: 10.2147/PPA.S133288

Pulmonary arterial hypertension (PAH) is a devastating disease and ultimately leads to right heart failure and premature death. A total of four classical targeted drugs, prostanoids, endothelin receptor antagonists (ERAs), phosphodiesterase 5 inhibitors (PDE-5Is), and soluble guanylate cyclase stimulator (sGCS), have been proved to improve exercise capacity and hemodynamics compared to placebo; however, direct head-to-head comparisons of these drugs are lacking. This network meta-analysis was conducted to comprehensively compare the efficacy of these targeted drugs for PAH. Medline, the Cochrane Library, and other Internet sources were searched for randomized clinical trials exploring the efficacy of targeted drugs for patients with PAH. The primary effective end point of this network meta-analysis was a 6-minute walk distance (6MWD). Thirty-two eligible trials including 6,758 patients were identified. There was a statistically significant improvement in 6MWD, mean pulmonary arterial pressure, pulmonary vascular resistance, and clinical worsening events associated with each of the four targeted drugs compared with placebo. Combination therapy improved 6MWD by 20.94 m (95% confidence interval [CI]: 6.94, 34.94; =0.003) vs prostanoids, and 16.94 m (95% CI: 4.41, 29.47; =0.008) vs ERAs. PDE-5Is improved 6MWD by 17.28 m (95% CI: 1.91, 32.65; =0.028) vs prostanoids, with a similar result with combination therapy. In addition, combination therapy reduced mean pulmonary artery pressure by 3.97 mmHg (95% CI: -6.06, -1.88;