Journal article
Comparative Effectiveness of Pharmacologic Interventions for Pulmonary Arterial Hypertension: A Systematic Review and Network Meta-Analysis
Chest, Vol.151(1), pp.90-105
01/2017
DOI: 10.1016/j.chest.2016.08.1461
PMCID: PMC5310124
PMID: 27615023
Abstract
We conducted a systematic review and network meta-analysis to examine comparative efficacy and tolerability of pharmacologic interventions for pulmonary arterial hypertension (PAH).
MEDLINE, 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.
Thirty-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.
Currently 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.
PROSPERO CRD42016036803.
Details
- Title: Subtitle
- Comparative Effectiveness of Pharmacologic Interventions for Pulmonary Arterial Hypertension: A Systematic Review and Network Meta-Analysis
- Creators
- Snigdha Jain - Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX. Electronic address: snigdha.jain@utsouthwestern.eduRohan Khera - Division of Cardiology, University of Texas Southwestern Medical Center, Dallas, TXSaket Girotra - Division of Cardiology, University of Iowa Carver College of Medicine, Iowa City, IADavid Badesch - Division of Pulmonary Sciences and Critical Care Medicine, University of Colorado Anschutz Medical Campus, Aurora, COZhen Wang - Knowledge and Evaluation Research Unit and the Robert D. and Patricia E. Kern Center for the Science of Health Care Delivery, Mayo Clinic, Rochester, MNMohammad Hassan Murad - Knowledge and Evaluation Research Unit and the Robert D. and Patricia E. Kern Center for the Science of Health Care Delivery, Mayo Clinic, Rochester, MNAmy Blevins - Hardin Library for the Health Sciences, University of Iowa Carver College of Medicine, Iowa City, IAGregory A Schmidt - Division of Pulmonary, Critical Care, and Occupational Medicine, University of Iowa Carver College of Medicine, Iowa City, IASiddharth Singh - Division of Biomedical Informatics, Department of Internal Medicine, University of California San Diego, La Jolla, CAAlicia K Gerke - Division of Pulmonary, Critical Care, and Occupational Medicine, University of Iowa Carver College of Medicine, Iowa City, IA
- Resource Type
- Journal article
- Publication Details
- Chest, Vol.151(1), pp.90-105
- DOI
- 10.1016/j.chest.2016.08.1461
- PMID
- 27615023
- PMCID
- PMC5310124
- ISSN
- 0012-3692
- eISSN
- 1931-3543
- Grant note
- P30 ES005605 / NIEHS NIH HHS T32 HL125247 / NHLBI NIH HHS T15 LM011271 / NLM NIH HHS K23 HL114640 / NHLBI NIH HHS K08 HL122527 / NHLBI NIH HHS UL1 TR001105 / NCATS NIH HHS
- Language
- English
- Date published
- 01/2017
- Academic Unit
- Pulmonary, Critical Care, and Occupational Medicine; Cardiovascular Medicine; Internal Medicine
- Record Identifier
- 9984094385102771
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