PMID- 24815795
OWN - NLM
STAT- MEDLINE
DCOM- 20150331
LR  - 20191210
IS  - 1557-3117 (Electronic)
IS  - 1053-2498 (Linking)
VI  - 33
IP  - 7
DP  - 2014 Jul
TI  - Long-term sildenafil added to intravenous epoprostenol in patients with pulmonary 
      arterial hypertension.
PG  - 689-97
LID - S1053-2498(14)00997-8 [pii]
LID - 10.1016/j.healun.2014.02.019 [doi]
AB  - BACKGROUND: In pulmonary arterial hypertension (PAH), adding oral sildenafil to 
      intravenous epoprostenol improved 6-minute walk distance (6MWD) and hemodynamics 
      and delayed time to clinical worsening in a 16-week randomized, 
      placebo-controlled trial (Pulmonary Arterial Hypertension Combination Study of 
      Epoprostenol and Sildenafil [PACES-1]). METHODS: Patients completing PACES-1 
      could receive sildenafil (titrated to 80 mg, three times daily, as tolerated) in 
      an open-label extension study (PACES-2) for >/= 3 years; additional therapy was 
      added according to investigator judgment. Survival and changes from PACES-1 
      baseline in World Health Organization Functional Class and 6MWD were captured. 
      RESULTS: In an open-label setting, 6MWD, an effort-dependent outcome measure, was 
      known to have improved or to have been maintained in 59%, 44%, and 33% of 
      patients at 1, 2, and 3 years, respectively; functional class was known to have 
      improved or to have been maintained in 73%, 59%, and 46%. At 3 years, 66% of 
      patients were known to be alive, 24% were known to have died, and 10% were lost 
      to follow-up. Patients with PACES-1 baseline 6MWD < 325 meters without 6MWD 
      improvement during the first 20 weeks of sildenafil treatment subsequently had 
      poorer survival. CONCLUSIONS: Although reliable assessments of safety and 
      efficacy require a long-term randomized trial, the addition of sildenafil to 
      background intravenous epoprostenol therapy appeared generally to be well 
      tolerated in PAH patients.
CI  - Copyright (c) 2014 International Society for Heart and Lung Transplantation. 
      Published by Elsevier Inc. All rights reserved.
FAU - Simonneau, Gerald
AU  - Simonneau G
AD  - University Paris-Sud, National Reference Center for Severe Pulmonary 
      Hypertension, Hopital de Bicetre, Le Kremlin-Bicetre, France. Electronic address: 
      gerald.simonneau@bct.aphp.fr.
FAU - Rubin, Lewis J
AU  - Rubin LJ
AD  - Department of Medicine, University of California at San Diego, La Jolla, 
      California.
FAU - Galie, Nazzareno
AU  - Galie N
AD  - Institute of Cardiology, Bologna University Hospital, Bologna, Italy.
FAU - Barst, Robyn J
AU  - Barst RJ
AD  - Division of Pediatric Cardiology, Columbia University, New York, New York.
FAU - Fleming, Thomas R
AU  - Fleming TR
AD  - Department of Biostatistics, University of Washington, Seattle, Washington.
FAU - Frost, Adaani
AU  - Frost A
AD  - Department of Medicine, Section of Pulmonary and Critical Care, Baylor College of 
      Medicine, Houston, Texas.
FAU - Engel, Peter
AU  - Engel P
AD  - Pulmonary Hypertension Program, The Christ Hospital, Cincinnati, Ohio.
FAU - Kramer, Mordechai R
AU  - Kramer MR
AD  - Pulmonary Institute, Rabin Medical Center, Petah Tikva, Israel.
FAU - Serdarevic-Pehar, Marjana
AU  - Serdarevic-Pehar M
AD  - Pfizer Inc, New York, New York.
FAU - Layton, Gary R
AU  - Layton GR
AD  - Worldwide Pharmaceutical Operations, Pfizer Ltd, Sandwich, Kent, United Kingdom.
FAU - Sitbon, Olivier
AU  - Sitbon O
AD  - University Paris-Sud, National Reference Center for Severe Pulmonary 
      Hypertension, Hopital de Bicetre, Le Kremlin-Bicetre, France.
FAU - Badesch, David B
AU  - Badesch DB
AD  - Division of Pulmonary Sciences and Critical Care Medicine, and Cardiology 
      Director, Pulmonary Hypertension Program, University of Colorado Denver, Denver, 
      Colorado.
CN  - PACES Study Group
LA  - eng
SI  - ClinicalTrials.gov/NCT00147641
PT  - Journal Article
PT  - Multicenter Study
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
DEP - 20140222
PL  - United States
TA  - J Heart Lung Transplant
JT  - The Journal of heart and lung transplantation : the official publication of the 
      International Society for Heart Transplantation
JID - 9102703
RN  - 0 (Antihypertensive Agents)
RN  - 0 (Phosphodiesterase 5 Inhibitors)
RN  - 0 (Piperazines)
RN  - 0 (Purines)
RN  - 0 (Sulfonamides)
RN  - BW9B0ZE037 (Sildenafil Citrate)
RN  - DCR9Z582X0 (Epoprostenol)
SB  - IM
MH  - Administration, Intravenous
MH  - Adult
MH  - Antihypertensive Agents/*administration & dosage/*therapeutic use
MH  - Dose-Response Relationship, Drug
MH  - Drug Therapy, Combination
MH  - Epoprostenol/*administration & dosage/*therapeutic use
MH  - Female
MH  - Follow-Up Studies
MH  - Hemodynamics/physiology
MH  - Humans
MH  - Hypertension, Pulmonary/*drug therapy/mortality/physiopathology
MH  - Longitudinal Studies
MH  - Male
MH  - Middle Aged
MH  - Outcome Assessment, Health Care
MH  - Phosphodiesterase 5 Inhibitors/*therapeutic use
MH  - Piperazines/*therapeutic use
MH  - Purines/therapeutic use
MH  - Sildenafil Citrate
MH  - Sulfonamides/*therapeutic use
MH  - Survival Rate
MH  - Time Factors
MH  - Treatment Outcome
MH  - Walking/physiology
OTO - NOTNLM
OT  - clinical trial
OT  - epoprostenol
OT  - pulmonary arterial hypertension
OT  - sildenafil
OT  - survival
EDAT- 2014/05/13 06:00
MHDA- 2015/04/01 06:00
CRDT- 2014/05/13 06:00
PHST- 2013/10/10 00:00 [received]
PHST- 2014/02/15 00:00 [revised]
PHST- 2014/02/16 00:00 [accepted]
PHST- 2014/05/13 06:00 [entrez]
PHST- 2014/05/13 06:00 [pubmed]
PHST- 2015/04/01 06:00 [medline]
AID - S1053-2498(14)00997-8 [pii]
AID - 10.1016/j.healun.2014.02.019 [doi]
PST - ppublish
SO  - J Heart Lung Transplant. 2014 Jul;33(7):689-97. doi: 
      10.1016/j.healun.2014.02.019. Epub 2014 Feb 22.