PMID- 15750042
OWN - NLM
STAT- MEDLINE
DCOM- 20050708
LR  - 20220409
IS  - 1073-449X (Print)
IS  - 1073-449X (Linking)
VI  - 171
IP  - 11
DP  - 2005 Jun 1
TI  - Sildenafil versus Endothelin Receptor Antagonist for Pulmonary Hypertension 
      (SERAPH) study.
PG  - 1292-7
AB  - RATIONALE: Phosphodiesterase type 5 (PDE5) inhibition has been proposed for the 
      treatment for pulmonary arterial hypertension (PAH). OBJECTIVE: This study 
      compared adding sildenafil, a PDE5 inhibitor, to conventional treatment with the 
      current practice of adding bosentan, an endothelin receptor antagonist. METHODS: 
      Twenty-six patients with PAH, idiopathic or associated with connective tissue 
      disease, World Health Organization (WHO) functional class III, were randomized in 
      a double-blind fashion to receive sildenafil (50 mg twice daily for 4 weeks, then 
      50 mg three times daily) or bosentan (62.5 mg twice daily for 4 weeks, then 125 
      mg twice daily) over 16 weeks. MEASUREMENTS: Changes in right ventricular (RV) 
      mass (using cardiovascular magnetic resonance), 6-minute walk distance, cardiac 
      function, brain natriuretic peptide, and Borg dyspnea index. MAIN RESULTS: When 
      analyzed by intention to treat, there were no significant differences between the 
      two treatment groups. One patient on sildenafil died suddenly. Patients on 
      sildenafil who completed the protocol showed significant changes from baseline, 
      namely, reductions in RV mass (-8.8 g; 95% confidence interval [CI], -2, -16; n = 
      13, p = 0.015) and plasma brain natriuretic peptide levels (-19.4 fmol x ml(-1); 
      95% CI, -5, -34; p = 0.014) and improvements in 6-minute walk distance (114 m; 
      95% CI, 67, 160; p = 0.0002), cardiac index (0.3 L x min(-1) x m(-2); 95% CI, 
      0.1, 0.4; p = 0.008), and systolic left ventricular eccentricity index (-0.2; 95% 
      CI, -0.02, -0.37; p = 0.031). Bosentan improved 6-minute walk distance (59 m; 95% 
      CI, 29, 89; n = 12, p = 0.001) and cardiac index (0.3; 95% CI, 0.1, 0.4; p = 
      0.008). CONCLUSIONS: Sildenafil added to conventional treatment reduces RV mass 
      and improves cardiac function and exercise capacity in patients with PAH, WHO 
      functional class III. Safety monitoring is important until more experience is 
      obtained.
FAU - Wilkins, Martin R
AU  - Wilkins MR
AD  - Experimental Medicine and Toxicology, Imperial College London, W12 0NN, UK. 
      m.wilkins@imperial.ac.uk
FAU - Paul, Gideon A
AU  - Paul GA
FAU - Strange, Julian W
AU  - Strange JW
FAU - Tunariu, Nina
AU  - Tunariu N
FAU - Gin-Sing, Wendy
AU  - Gin-Sing W
FAU - Banya, Winston A
AU  - Banya WA
FAU - Westwood, Mark A
AU  - Westwood MA
FAU - Stefanidis, Alexander
AU  - Stefanidis A
FAU - Ng, Leong L
AU  - Ng LL
FAU - Pennell, Dudley J
AU  - Pennell DJ
FAU - Mohiaddin, Raad H
AU  - Mohiaddin RH
FAU - Nihoyannopoulos, Petros
AU  - Nihoyannopoulos P
FAU - Gibbs, J Simon R
AU  - Gibbs JS
LA  - eng
PT  - Clinical Trial
PT  - Comparative Study
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
DEP - 20050304
PL  - United States
TA  - Am J Respir Crit Care Med
JT  - American journal of respiratory and critical care medicine
JID - 9421642
RN  - 0 (Antihypertensive Agents)
RN  - 0 (Endothelin Receptor Antagonists)
RN  - 0 (Phosphodiesterase Inhibitors)
RN  - 0 (Piperazines)
RN  - 0 (Purines)
RN  - 0 (Sulfonamides)
RN  - 0 (Sulfones)
RN  - 114471-18-0 (Natriuretic Peptide, Brain)
RN  - BW9B0ZE037 (Sildenafil Citrate)
RN  - Q326023R30 (Bosentan)
SB  - IM
CIN - Am J Respir Crit Care Med. 2005 Jun 1;171(11):1199-201. PMID: 15914567
MH  - Adult
MH  - Antihypertensive Agents/*therapeutic use
MH  - Bosentan
MH  - Double-Blind Method
MH  - *Endothelin Receptor Antagonists
MH  - Exercise Tolerance/drug effects
MH  - Female
MH  - Heart Ventricles/pathology
MH  - Humans
MH  - Hypertension, Pulmonary/blood/*drug therapy/pathology
MH  - Male
MH  - Middle Aged
MH  - Natriuretic Peptide, Brain/blood
MH  - Organ Size/drug effects
MH  - Phosphodiesterase Inhibitors/*therapeutic use
MH  - Piperazines/*therapeutic use
MH  - Purines
MH  - Quality of Life
MH  - Sildenafil Citrate
MH  - Sulfonamides/*therapeutic use
MH  - Sulfones
MH  - Treatment Outcome
EDAT- 2005/03/08 09:00
MHDA- 2005/07/09 09:00
CRDT- 2005/03/08 09:00
PHST- 2005/03/08 09:00 [pubmed]
PHST- 2005/07/09 09:00 [medline]
PHST- 2005/03/08 09:00 [entrez]
AID - 200410-1411OC [pii]
AID - 10.1164/rccm.200410-1411OC [doi]
PST - ppublish
SO  - Am J Respir Crit Care Med. 2005 Jun 1;171(11):1292-7. doi: 
      10.1164/rccm.200410-1411OC. Epub 2005 Mar 4.