PMID- 28279499
OWN - NLM
STAT- MEDLINE
DCOM- 20171130
LR  - 20171130
IS  - 1874-1754 (Electronic)
IS  - 0167-5273 (Linking)
VI  - 235
DP  - 2017 May 15
TI  - Tadalafil in idiopathic or heritable pulmonary arterial hypertension (PAH) 
      compared to PAH associated with connective tissue disease.
PG  - 67-72
LID - S0167-5273(17)31124-5 [pii]
LID - 10.1016/j.ijcard.2017.02.094 [doi]
AB  - BACKGROUND: The primary objective of this post hoc analysis was to evaluate 
      clinical outcomes of tadalafil in patients with pulmonary arterial hypertension 
      (PAH) associated with connective tissue disease (CTD-PAH) compared with patients 
      with idiopathic/heritable PAH (I/H-PAH) for primary and key secondary efficacy 
      endpoints, and safety. This analysis included adult patients with CTD-PAH or 
      I/H-PAH who participated in the PHIRST and PHIRST-2 studies. METHODS: Patients 
      were randomized 1:1:1:1:1 to tadalafil (2.5, 10, 20, or 40mg) or placebo in the 
      PHIRST study and the majority of these patients were subsequently assigned 40mg 
      in PHIRST-2. Patients taking 20mg in PHIRST without demonstrating clinical 
      worsening continued on 20mg in PHIRST-2. Outcomes analyzed included 6MWD, WHO-FC, 
      and incidence and time to first occurrence of clinical worsening. Safety was 
      assessed through evaluation of adverse events (AEs), clinical laboratory data, 
      electrocardiograms, and physical examinations. RESULTS: Increased 6MWD in PHIRST 
      was maintained in both CTD-PAH and I/H-PAH subgroups for 52weeks. Patients with 
      CTD-PAH tended to be older, were more likely female, had lower exercise capacity, 
      were more likely to have clinical worsening, and experienced AEs more frequently 
      than patients with I/H-PAH. CONCLUSION: The effect of tadalafil treatment in 
      patients enrolled in both PHIRST studies was detectable for both I/H-PAH and 
      CTD-PAH subgroups. In general, subgroup differences were modest. Patients with 
      CTD-PAH may perform less well than patients with I/H-PAH in safety and efficacy 
      measures in all treatment groups, which is similar to other studies demonstrating 
      a worse prognosis for patients with CTD-PAH.
CI  - Copyright (c) 2017. Published by Elsevier B.V.
FAU - Galie, Nazzareno
AU  - Galie N
AD  - Department of Experimental, Diagnostic and Specialty Medicine (DIMES), University 
      of Bologna, Bologna, Italy. Electronic address: nazzareno.galie@unibo.it.
FAU - Denton, Christopher P
AU  - Denton CP
AD  - Centre for Rheumatology at the Royal Free, and University College Medical School, 
      Hampstead, London, United Kingdom.
FAU - Dardi, Fabio
AU  - Dardi F
AD  - Department of Experimental, Diagnostic and Specialty Medicine (DIMES), University 
      of Bologna, Bologna, Italy.
FAU - Manes, Alessandra
AU  - Manes A
AD  - Department of Experimental, Diagnostic and Specialty Medicine (DIMES), University 
      of Bologna, Bologna, Italy.
FAU - Mazzanti, Gaia
AU  - Mazzanti G
AD  - Department of Experimental, Diagnostic and Specialty Medicine (DIMES), University 
      of Bologna, Bologna, Italy.
FAU - Li, Baohui
AU  - Li B
AD  - Eli Lilly and Company, Indianapolis, IN, USA.
FAU - Varanese, Lucio
AU  - Varanese L
AD  - Eli Lilly and Company, Indianapolis, IN, USA.
FAU - Esler, Anne
AU  - Esler A
AD  - inVentiv Clinical Solutions, LLC, Indianapolis, IN, USA.
FAU - Harmon, Cathi
AU  - Harmon C
AD  - Eli Lilly and Company, Indianapolis, IN, USA.
FAU - Palazzini, Massimiliano
AU  - Palazzini M
AD  - Department of Experimental, Diagnostic and Specialty Medicine (DIMES), University 
      of Bologna, Bologna, Italy.
LA  - eng
PT  - Journal Article
PT  - Randomized Controlled Trial
DEP - 20170222
PL  - Netherlands
TA  - Int J Cardiol
JT  - International journal of cardiology
JID - 8200291
RN  - 0 (Vasodilator Agents)
RN  - 742SXX0ICT (Tadalafil)
SB  - IM
MH  - Connective Tissue Diseases/*complications
MH  - Dose-Response Relationship, Drug
MH  - Drug Monitoring/methods
MH  - Drug-Related Side Effects and Adverse Reactions/*diagnosis
MH  - Electrocardiography/methods
MH  - *Familial Primary Pulmonary Hypertension/diagnosis/drug therapy
MH  - Female
MH  - Humans
MH  - *Hypertension, Pulmonary/diagnosis/drug therapy/etiology
MH  - Male
MH  - Middle Aged
MH  - Physical Examination/methods
MH  - *Tadalafil/administration & dosage/adverse effects
MH  - Treatment Outcome
MH  - Vasodilator Agents/administration & dosage/adverse effects
OTO - NOTNLM
OT  - Associated PAH
OT  - Heritable
OT  - Idiopathic
OT  - PHIRST
OT  - PHIRST-2
EDAT- 2017/03/11 06:00
MHDA- 2017/12/01 06:00
CRDT- 2017/03/11 06:00
PHST- 2016/08/18 00:00 [received]
PHST- 2017/01/13 00:00 [revised]
PHST- 2017/02/20 00:00 [accepted]
PHST- 2017/03/11 06:00 [pubmed]
PHST- 2017/12/01 06:00 [medline]
PHST- 2017/03/11 06:00 [entrez]
AID - S0167-5273(17)31124-5 [pii]
AID - 10.1016/j.ijcard.2017.02.094 [doi]
PST - ppublish
SO  - Int J Cardiol. 2017 May 15;235:67-72. doi: 10.1016/j.ijcard.2017.02.094. Epub 
      2017 Feb 22.