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Original Research |

Comparative Effectiveness of Pharmacological Interventions for Pulmonary Arterial Hypertension: A Systematic Review and Network Meta-Analysis

Snigdha Jain, M.D; Rohan Khera, M.D; Saket Girotra, M.D., S.M; David Badesch, M.D; Zhen Wang, Ph.D; Mohammad Hassan Murad, M.D; Amy Blevins, M.A.L.S; Gregory A. Schmidt, M.D; Siddharth Singh, M.D; Alicia K. Gerke, M.D
Author and Funding Information

Financial Disclosures: Dr. Gerke is supported by a career development award from the NHLBI (K23HL114640). Dr. Girotra is supported by a career development award (K08HL122527) from the National Heart Lung, and Blood Institute (NHLBI). Dr. Singh is supported by the National Library of Medicine/National Institute of Health training grant T15LM011271. Dr. Khera received support from the National Center for Advancing Translational Sciences of the National Institutes of Health under award Number UL1TR001105. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH.

Conflict of Interest Disclosure: Dr. Badesch serves as a consultant / advisory board member / steering committee member for Actelion/ CoTherix, Gilead, Pfizer, United Therapeutics/ Lung Rx, Bayer, Arena and Ikaria / Belleraphon. No conflicts of interest exist for authors SJ, RK, SS, AB, MHM, ZW, GS and AG.

Registration: PROSPERO CRD42016036803

1Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX

2Divsion of Cardiology, University of Texas Southwestern Medical Center, Dallas, TX

3Division of Cardiology, University of Iowa Carver College of Medicine, Iowa City, IA

4Division of Pulmonary Sciences and Critical Care Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO

5Knowledge and Evaluation Research Unit, Robert D. and Patricia E. Kern Center for the Science of Health Care Delivery, Mayo Clinic, Rochester, MN

6Hardin Library for the Health Sciences, University of Iowa Carver College of Medicine, Iowa City, IA

7Division of Pulmonary, Critical Care and Occupational Medicine, University of Iowa Carver College of Medicine, Iowa City, IA

8Division of Biomedical Informatics, Department of Internal Medicine, University of California San Diego, La Jolla, CA

∗∗Corresponding author: Snigdha Jain, MD, Assistant Professor, Internal Medicine, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd, Dallas, TX – 75390.


Copyright 2016, . All Rights Reserved.


Chest. 2016. doi:10.1016/j.chest.2016.08.1461
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Abstract

Background  We conducted a systematic review and network meta-analysis to examine comparative efficacy and tolerability of pharmacological interventions for pulmonary arterial hypertension (PAH).

Methods  MEDLINE, Cochrane register, EMBASE, CINAHL and clinicaltrials.gov were searched (January 1, 1990 - March 3, 2016). Randomized controlled trials (RCTs) of approved pharmacological agents - endothelin receptor antagonists (ERA), phosphodiesterase inhibitors (PDE5i), oral/inhaled and intravenous/subcutaneous prostanoids, riociguat, and selexipag, alone or in combination for pulmonary arterial hypertension (PAH) reporting at least one efficacy outcome were selected.

Results  31 RCTs with 6,565 patients were selected. In network meta-analysis, compared to 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), 3.9% with ERA+PDE5i (RR 0.27, 95% CI 0.14,0.52) and 5.7% with PDE5i (RR 0.39, 95% CI 0.24,0.62). For improvement in functional status, compared to 16.2% in the placebo group, improvement in at least 1 NYHA/WHO functional class was estimated at 81.8% with intravenous/subcutaneous prostanoids (RR 5.06, 95% CI 2.32,11.04), 28.3% with ERA+PDE5i (RR 1.75, 95% CI 1.05,2.92) and 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 oral/inhaled prostanoids (RR 2.92, 95% CI 1.68,5.06) and selexipag (RR 2.06, 95% CI 1.04,3.88) compared to placebo.

Conclusions  Currently approved pharmacological agents have varying effects on morbidity and functional status in patients with PAH. Future comparative effectiveness trials are warranted with a focus on patient-centered approach to therapy.


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