Comparative Effectiveness of Pharmacologic Interventions for Pulmonary Arterial Hypertension: A Systematic Review and Network Meta-Analysis.
BACKGROUND
We conducted a systematic review and network meta-analysis to examine comparative efficacy and tolerability of pharmacologic interventions for pulmonary arterial hypertension (PAH).


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.


BACKGROUND
PROSPERO CRD42016036803.
Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX. Electronic address: snigdha.jain@utsouthwestern.edu.
Snigdha
S
Jain
Division of Cardiology, University of Texas Southwestern Medical Center, Dallas, TX.
Rohan
R
Khera
Division of Cardiology, University of Iowa Carver College of Medicine, Iowa City, IA.
Saket
S
Girotra
Division of Pulmonary Sciences and Critical Care Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO.
David
D
Badesch
Knowledge and Evaluation Research Unit and the Robert D. and Patricia E. Kern Center for the Science of Health Care Delivery, Mayo Clinic, Rochester, MN.
Zhen
Z
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, MN.
Mohammad Hassan
MH
Murad
Hardin Library for the Health Sciences, University of Iowa Carver College of Medicine, Iowa City, IA.
Amy
A
Blevins
Division of Pulmonary, Critical Care, and Occupational Medicine, University of Iowa Carver College of Medicine, Iowa City, IA.
Gregory A
GA
Schmidt
Division of Biomedical Informatics, Department of Internal Medicine, University of California San Diego, La Jolla, CA.
Siddharth
S
Singh
Division of Pulmonary, Critical Care, and Occupational Medicine, University of Iowa Carver College of Medicine, Iowa City, IA.
Alicia K
AK
Gerke
D006801:Humans; D000959:Antihypertensive Agents / Q000145:classification / Q000494:pharmacology; D057186:Comparative Effectiveness Research; D006976:Hypertension, Pulmonary / Q000188:drug therapy
D000959:Antihypertensive Agents
comparative efficacy; network meta-analysis; pulmonary arterial hypertension