PMID- 31735058
OWN - NLM
STAT- MEDLINE
DCOM- 20200907
LR  - 20200907
IS  - 1542-6270 (Electronic)
IS  - 1060-0280 (Linking)
VI  - 54
IP  - 5
DP  - 2020 May
TI  - A Bayesian Network Meta-analysis of Add-on Drug Therapies Specific for Pulmonary 
      Arterial Hypertension.
PG  - 423-433
LID - 10.1177/1060028019888760 [doi]
AB  - Background: Recently published meta-analyses did not discriminate between drug 
      agents used for initial and sequential combination therapy. Objective: To assess 
      the comparative efficacy of drugs specific for the treatment of pulmonary 
      arterial hypertension (PAH) as add-on therapies based on 6-minute walk distance 
      (6MWD), all-cause mortality, and discontinuation due to adverse events (AEs). 
      Methods: EMBASE, PubMed, Cochrane Library, and ClinicalTrials.gov were searched 
      until December 9, 2018, for the randomized, placebo-controlled clinical trials 
      (RCTs) conducted on primarily adult patients diagnosed with PAH. Data extracted 
      from applicable RCTs were as follows: for 6MWD mean change from baseline, the 
      total number of patients, and the number of patients with events, per treatment. 
      Network meta-analysis (NMA) was conducted in a Bayesian framework. Results: A 
      total of 16 RCTs were eligible for analysis, with 4112 patients. Add-on therapy 
      with tadalafil or inhaled treprostinil performed better than endothelin receptor 
      antagonists alone [27 m; 95% credible interval (CrI): (11, 43); and 19 m; 95% 
      CrI: (10, 27); respectively]. Add-on therapy with macitentan or bosentan 
      performed better than phosphodiesterase type 5 inhibitors alone [26 m; 95% CrI: 
      (6.4, 45); and 22 m; 95% CrI: (5.1, 38); respectively]. Differences in all-cause 
      mortality and discontinuation due to AEs were nonsignificant. Conclusion and 
      Relevance: Our NMA evaluated efficacy and safety of add-on therapies in patients 
      with PAH. None of the previous meta-analyses evaluated RCTs focusing solely on 
      patients pretreated with another PAH-specific drug therapy. Our results support 
      guideline recommendations on combination therapy in PAH patients and add the 
      quantitative perspective on which sequential therapy demonstrated the greatest 
      effect size.
FAU - Petrovic, Maja
AU  - Petrovic M
AUID- ORCID: 0000-0002-5483-0179
AD  - Krka, d. d., Novo mesto, Slovenia.
AD  - University of Ljubljana, Slovenia.
FAU - Locatelli, Igor
AU  - Locatelli I
AUID- ORCID: 0000-0002-0052-8986
AD  - University of Ljubljana, Slovenia.
LA  - eng
PT  - Journal Article
PT  - Systematic Review
DEP - 20191118
PL  - United States
TA  - Ann Pharmacother
JT  - The Annals of pharmacotherapy
JID - 9203131
RN  - 0 (Antihypertensive Agents)
RN  - 0 (Endothelin Receptor Antagonists)
RN  - 0 (Phosphodiesterase 5 Inhibitors)
RN  - 0 (Pyrimidines)
RN  - 0 (Sulfonamides)
RN  - DCR9Z582X0 (Epoprostenol)
RN  - Q326023R30 (Bosentan)
RN  - RUM6K67ESG (treprostinil)
RN  - Z9K9Y9WMVL (macitentan)
SB  - IM
MH  - Adult
MH  - Antihypertensive Agents/administration & dosage/adverse effects/*therapeutic use
MH  - Bayes Theorem
MH  - Bosentan/administration & dosage/adverse effects/therapeutic use
MH  - Drug Therapy, Combination
MH  - Endothelin Receptor Antagonists/administration & dosage/adverse 
      effects/*therapeutic use
MH  - Epoprostenol/administration & dosage/adverse effects/analogs & 
      derivatives/therapeutic use
MH  - Humans
MH  - Male
MH  - *Network Meta-Analysis
MH  - Phosphodiesterase 5 Inhibitors/administration & dosage/adverse 
      effects/*therapeutic use
MH  - Practice Guidelines as Topic
MH  - Pulmonary Arterial Hypertension/*drug therapy
MH  - Pyrimidines/administration & dosage/adverse effects/therapeutic use
MH  - Sulfonamides/administration & dosage/adverse effects/therapeutic use
MH  - Treatment Outcome
OTO - NOTNLM
OT  - add-on therapy
OT  - combination
OT  - comparative effectiveness research
OT  - drug therapy
OT  - network meta-analysis
OT  - pulmonary arterial hypertension
EDAT- 2019/11/19 06:00
MHDA- 2020/09/08 06:00
CRDT- 2019/11/19 06:00
PHST- 2019/11/19 06:00 [pubmed]
PHST- 2020/09/08 06:00 [medline]
PHST- 2019/11/19 06:00 [entrez]
AID - 10.1177/1060028019888760 [doi]
PST - ppublish
SO  - Ann Pharmacother. 2020 May;54(5):423-433. doi: 10.1177/1060028019888760. Epub 
      2019 Nov 18.