PMID- 32691518
OWN - NLM
STAT- MEDLINE
DCOM- 20211102
LR  - 20211102
IS  - 1756-185X (Electronic)
IS  - 1756-1841 (Linking)
VI  - 23
IP  - 10
DP  - 2020 Oct
TI  - Effectiveness and safety of endothelin receptor antagonists, alone and in 
      combination therapy, in the pulmonary arterial hypertension-connective tissue 
      disease subtype: A systematic review and meta-analysis.
PG  - 1276-1287
LID - 10.1111/1756-185X.13916 [doi]
AB  - INTRODUCTION: There is limited information regarding the effectiveness of 
      endothelin receptor antagonists (ERA) in patients with connective tissue 
      disease-pulmonary arterial hypertension (CTD-PAH), a condition that is 
      characterized by poorer clinical outcomes compared to other PAH subtypes. 
      OBJECTIVE: To conduct a systematic review and meta-analysis of the effectiveness 
      and safety of ERA in CTD-PAH. METHODS: A literature search, using MEDLINE, 
      COCHRANE, CINAHL and EMBASE databases was conducted, from inception to May 2019 
      to identify randomized control studies of ERA, as monotherapy or in combination 
      with phosphodiesterase type 5 inhibitors (PDE5i), in CTD-PAH. A protocol was 
      registered in PROSPERO (CRD42019136956). Efficacy outcomes, including the 
      6-minute walk distance (6MWD) and composite clinical failure endpoints (CFE), and 
      safety outcomes were evaluated. RESULTS: A total of 13 studies, including 784 
      CTD-PAH participants, were identified. ERA, as monotherapy, did not reduce the 
      risk of CFE compared to placebo (odds ratio [OR] 0.77, 95% CI 0.50-1.19, P = 
      .25). By contrast, combination therapy (ERA + PDE5i) significantly reduced the 
      risk of developing CFE vs monotherapy (OR 0.54, 95% CI 0.32-0.90, P = .02). 6MWD 
      did not improve when comparing monotherapy vs placebo (+17.41 m; 95% CI 
      -19.83-54.66) P = .36) or combination therapy vs monotherapy (+13.17 m; 95% CI 
      -16.44-42.78, P = .38). ERA-related adverse events rates in CTD-PAH and general 
      PAH cohorts were comparable. CONCLUSIONS: ERA, when used in combination with 
      PDE5is, are associated with reduced risk of CFE, but no significant changes in 
      6MWD, in CTD-PAH. This warrants further studies investigating early combination 
      therapy as a standard of care in this group.
CI  - (c) 2020 Asia Pacific League of Associations for Rheumatology and John Wiley & Sons 
      Australia, Ltd.
FAU - Shivakumar, Senthuran
AU  - Shivakumar S
AUID- ORCID: 0000-0003-4855-0493
AD  - Department of Clinical Pharmacology, Flinders Medical Centre, Adelaide, South 
      Australia, Australia.
FAU - Thynne, Tilenka R
AU  - Thynne TR
AD  - Department of Clinical Pharmacology, Flinders Medical Centre, Adelaide, South 
      Australia, Australia.
AD  - Discipline of Clinical Pharmacology, College of Medicine and Public Health, 
      Flinders University, Adelaide, South Australia, Australia.
FAU - Mohammadi, Leila
AU  - Mohammadi L
AD  - Flinders University, Adelaide, South Australia, Australia.
FAU - Burdeniuk, Christine
AU  - Burdeniuk C
AD  - Department of Cardiology, Flinders Medical Centre, Adelaide, South Australia, 
      Australia.
FAU - Mangoni, Arduino A
AU  - Mangoni AA
AUID- ORCID: 0000-0001-8699-1412
AD  - Department of Clinical Pharmacology, Flinders Medical Centre, Adelaide, South 
      Australia, Australia.
AD  - Discipline of Clinical Pharmacology, College of Medicine and Public Health, 
      Flinders University, Adelaide, South Australia, Australia.
LA  - eng
PT  - Journal Article
PT  - Meta-Analysis
PT  - Systematic Review
DEP - 20200721
PL  - England
TA  - Int J Rheum Dis
JT  - International journal of rheumatic diseases
JID - 101474930
RN  - 0 (Antihypertensive Agents)
RN  - 0 (Endothelin Receptor Antagonists)
RN  - 0 (Phosphodiesterase 5 Inhibitors)
SB  - IM
MH  - Antihypertensive Agents/*therapeutic use
MH  - Connective Tissue Diseases/*complications/drug therapy
MH  - Drug Therapy, Combination
MH  - Endothelin Receptor Antagonists/*therapeutic use
MH  - Humans
MH  - Phosphodiesterase 5 Inhibitors/*therapeutic use
MH  - Pulmonary Arterial Hypertension/*drug therapy/*etiology
MH  - Treatment Outcome
OTO - NOTNLM
OT  - combination therapy
OT  - connective tissue disease
OT  - endothelin receptor antagonist
OT  - phosphodiesterase inhibitors
OT  - pulmonary arterial hypertension
EDAT- 2020/07/22 06:00
MHDA- 2021/11/03 06:00
CRDT- 2020/07/22 06:00
PHST- 2020/01/25 00:00 [received]
PHST- 2020/05/19 00:00 [revised]
PHST- 2020/06/18 00:00 [accepted]
PHST- 2020/07/22 06:00 [pubmed]
PHST- 2021/11/03 06:00 [medline]
PHST- 2020/07/22 06:00 [entrez]
AID - 10.1111/1756-185X.13916 [doi]
PST - ppublish
SO  - Int J Rheum Dis. 2020 Oct;23(10):1276-1287. doi: 10.1111/1756-185X.13916. Epub 
      2020 Jul 21.