Comparative Effectiveness of Pharmacologic Interventions for Pulmonary Arterial Hypertension

A Systematic Review and Network Meta-Analysis

Snigdha Jain, Rohan Khera, Saket Girotra, David Badesch, Zhen Wang, Mohammad Hassan Murad, Amy Blevins, Gregory A. Schmidt, Siddharth Singh, Alicia K. Gerke

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

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. Registration PROSPERO CRD42016036803

Original languageEnglish (US)
Pages (from-to)90-105
Number of pages16
JournalChest
Volume151
Issue number1
DOIs
StatePublished - Jan 1 2017

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Pulmonary Hypertension
Odds Ratio
Prostaglandins
Placebos
Randomized Controlled Trials
Phosphodiesterase Inhibitors
Network Meta-Analysis
MEDLINE
Morbidity
Mortality
Endothelin Receptor Antagonists
Therapeutics

Keywords

  • comparative efficacy
  • network meta-analysis
  • pulmonary arterial hypertension

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine
  • Critical Care and Intensive Care Medicine
  • Cardiology and Cardiovascular Medicine

Cite this

Comparative Effectiveness of Pharmacologic Interventions for Pulmonary Arterial Hypertension : A Systematic Review and Network Meta-Analysis. / Jain, Snigdha; Khera, Rohan; Girotra, Saket; Badesch, David; Wang, Zhen; Murad, Mohammad Hassan; Blevins, Amy; Schmidt, Gregory A.; Singh, Siddharth; Gerke, Alicia K.

In: Chest, Vol. 151, No. 1, 01.01.2017, p. 90-105.

Research output: Contribution to journalArticle

Jain, S, Khera, R, Girotra, S, Badesch, D, Wang, Z, Murad, MH, Blevins, A, Schmidt, GA, Singh, S & Gerke, AK 2017, 'Comparative Effectiveness of Pharmacologic Interventions for Pulmonary Arterial Hypertension: A Systematic Review and Network Meta-Analysis', Chest, vol. 151, no. 1, pp. 90-105. https://doi.org/10.1016/j.chest.2016.08.1461
Jain, Snigdha ; Khera, Rohan ; Girotra, Saket ; Badesch, David ; Wang, Zhen ; Murad, Mohammad Hassan ; Blevins, Amy ; Schmidt, Gregory A. ; Singh, Siddharth ; Gerke, Alicia K. / Comparative Effectiveness of Pharmacologic Interventions for Pulmonary Arterial Hypertension : A Systematic Review and Network Meta-Analysis. In: Chest. 2017 ; Vol. 151, No. 1. pp. 90-105.
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AU - Badesch, David

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AU - Murad, Mohammad Hassan

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N2 - 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. Registration PROSPERO CRD42016036803

AB - 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. Registration PROSPERO CRD42016036803

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