• Snigdha Jain, Rohan Khera, Saket Girotra, David Badesch, Zhen Wang, Mohammad Hassan Murad, Amy Blevins, Gregory A Schmidt, Siddharth Singh, and Alicia K Gerke.
• Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX. Electronic address: snigdha.jain@utsouthwestern.edu.
• Chest. 2017 Jan 1; 151 (1): 90-105.

BackgroundWe conducted a systematic review and network meta-analysis to examine comparative efficacy and tolerability of pharmacologic interventions for pulmonary arterial hypertension (PAH).MethodsMEDLINE, the Cochrane Register, EMBASE, CINAHL, and clinicaltrials.gov were searched (January 1, 1990 to March 3, 2016). Randomized controlled trials (RCTs) studying the approved pharmacologic agents endothelin receptor antagonists (ERA), phosphodiesterase inhibitors (PDE5i), the oral/inhaled (PO/INH) and IV/subcutaneous (SC) prostanoids, and riociguat and selexipag, alone or in combination, for pulmonary arterial hypertension (PAH) and reporting at least one efficacy outcome were selected.ResultsThirty-one RCTs with 6,565 patients were selected. In network meta-analysis, when compared with a median placebo rate of 14.5%, clinical worsening was estimated at 2.8% with riociguat (risk ratio [RR], 0.19; 95% CI, 0.05-0.76); at 3.9% with ERA + PDE5i (RR, 0.27; 95% CI, 0.14-0.52), and at 5.7% with PDE5i (RR, 0.39; 95% CI, 0.24-0.62). For improvement in functional status, when compared with 16.2% in the placebo group, improvement in at least one New York Heart Association/World Health Organization (NYHA/WHO) functional class was estimated at 81.8% with IV/SC prostanoids (RR, 5.06; 95% CI, 2.3211.04), at 28.3% with ERA + PDE5i (RR, 1.75; 95% CI, 1.05-2.92), and at 25.2% with ERA (RR, 1.56; 95% CI, 1.22-2.00). Differences in mortality were not significant. Adverse events leading to discontinuation of therapy were highest with the PO/INH prostanoids (RR, 2.92; 95% CI, 1.68-5.06) and selexipag (RR, 2.06; 95% CI, 1.04-3.88) compared with placebo.ConclusionsCurrently approved pharmacologic agents have varying effects on morbidity and functional status in patients with PAH. Future comparative effectiveness trials are warranted with a focus on a patient-centered approach to therapy.RegistrationPROSPERO CRD42016036803.Copyright © 2016 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.

26 keywords...

hide…