The effects of oral treatment for systemic sclerosis related pulmonary arterial hypertension: A systematic review and meta-analysis

Mod Rheumatol. 2021 Jan;31(1):151-161. doi: 10.1080/14397595.2019.1704125. Epub 2020 Jan 4.

Abstract

Objectives: The usage of oral therapies, endothelin receptor antagonists (ERAs), phosphodiesterase type-5 (PDE-5) inhibitors and prostaglandin analogs has resulted in improved outcomes in patients with pulmonary arterial hypertension related to systemic sclerosis (SSc-PAH). However, the optimal therapeutics have not been determined.

Methods: A systematic searching in the databases of Medline (PubMed), Embase, the Cochrane Library (Central) and unpublished clinical trials (clinicaltrials.gov) was conducted to identify the clinical studies with oral treatment for SSc-PAH patients published before 1 June 2019. The data were extracted and the quality was assessed. The main outcomes are exercise capacity and hemodynamic parameters, which were synthesized and analyzed.

Results: In total, 27 clinical trials were enrolled for further analysis. It was demonstrated that bosentan treatment, the widely used drug for PAH, might improve the exercise capacity and pulmonary arterial pressure (PAP) and pulmonary vascular resistance (PVR) in this clinical setting, although without significant difference. Meanwhile, the usage of prostaglandin analogs could improve the parameters mentioned above. Furthermore, combined therapy with ambrisentan and tadalafil significantly increased the treatment efficacy of key parameters in SSc-PAH patients compared with basic treatment.

Conclusion: This meta-analysis reveals that combination therapy might provide more benefits to exercise capacity and hemodynamic parameters in SSc-PAH patients. Still more RCTs are needed to provide more solid evidence.

Keywords: Systemic sclerosis; exercise capacity; hemodynamics functions; meta-analysis; pulmonary arterial hypertension.

Publication types

  • Meta-Analysis
  • Systematic Review

MeSH terms

  • Administration, Oral
  • Drug Therapy, Combination
  • Endothelin Receptor Antagonists / pharmacology*
  • Humans
  • Phosphodiesterase 5 Inhibitors / pharmacology*
  • Prostaglandins, Synthetic / pharmacology*
  • Pulmonary Arterial Hypertension* / drug therapy
  • Pulmonary Arterial Hypertension* / etiology
  • Pulmonary Arterial Hypertension* / physiopathology
  • Scleroderma, Systemic / complications*

Substances

  • Endothelin Receptor Antagonists
  • Phosphodiesterase 5 Inhibitors
  • Prostaglandins, Synthetic