Atrial septal defects versus ventricular septal defects in BREATHE-5, a placebo-controlled study of pulmonary arterial hypertension related to Eisenmenger's syndrome: a subgroup analysis.
BACKGROUND
Eisenmenger's syndrome (ES) is the most advanced form of pulmonary arterial hypertension related to congenital heart disease. Evolution of pulmonary vascular disease differs markedly between patients with atrial septal defects (ASD) versus ventricular septal defects (VSD), potentially affecting response to treatment. We compared the effects of bosentan and placebo in patients with isolated ASD (ASD subgroup) versus patients with isolated VSD or both defects (VSD subgroup).


METHODS
Post-hoc analysis of a 16-week, multicenter, randomized, double-blind, placebo-controlled trial was performed. Fifty-four patients (13: ASDs, 36: VSDs, 5: VSD+ASD) were randomized to bosentan 62.5 mg bid for four weeks (uptitrated to 125 mg bid thereafter) or placebo. Main outcome measures were: indexed pulmonary vascular resistance (PVRi), exercise capacity, mean pulmonary artery pressure (mPAP), pulmonary blood flow index (Qpi), and changes in oxygen saturation (SpO₂).


RESULTS
Placebo-corrected median (95% CI) treatment effects on PVRi were -544.0 dyn·s·cm⁻⁵ (-1593.8, 344.7) and -436.4 dyn·s·cm⁻⁵ (-960.0, 167.0) in the ASD and VSD subgroups, respectively. Effects of bosentan on exercise capacity and mPAP were similar in both subgroups. No changes in SpO₂ or Qpi were observed in either bosentan or placebo subgroups.


CONCLUSIONS
Improvements in exercise capacity and cardiopulmonary hemodynamics, without desaturation, were observed in ES patients with both ASDs and VSDs. Although not reaching statistical significance, improvements were similar to those in the BREATHE-5 analyses, suggesting that the location of septal defects is not a key determinant of treatment response. These data further support the use of bosentan for the treatment of ES, independent of shunt location.
Berger
Rolf M F
RM
University Medical Center, University of Groningen, Groningen, The Netherlands. r.m.f.berger@bkk.umcg.nl
Beghetti
Maurice
M
Galiè
Nazzareno
N
Gatzoulis
Michael A
MA
Granton
John
J
Lauer
Andrea
A
Chiossi
Eleonora
E
Landzberg
Michael
M
D000328:Adult; D000959:Antihypertensive Agents / Q000627:therapeutic use*; D000077300:Bosentan; D001900:Boston; D002170:Canada; D004311:Double-Blind Method; D004541:Eisenmenger Complex / Q000150:complications* / Q000503:physiopathology; D015444:Exercise; D005260:Female; D006344:Heart Septal Defects, Atrial / Q000150:complications* / Q000503:physiopathology; D006345:Heart Septal Defects, Ventricular / Q000150:complications* / Q000503:physiopathology; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D006976:Hypertension, Pulmonary / Q000188:drug therapy* / Q000209:etiology* / Q000503:physiopathology; D007558:Italy; D008297:Male; D008875:Middle Aged; D009426:Netherlands; D009864:Ontario; D010092:Oximetry; D011652:Pulmonary Circulation / Q000187:drug effects; D011669:Pulmonary Wedge Pressure / Q000187:drug effects; D013449:Sulfonamides / Q000627:therapeutic use*; D013557:Switzerland; D016896:Treatment Outcome; D006113:United Kingdom; D014655:Vascular Resistance / Q000187:drug effects
D000959:Antihypertensive Agents; D013449:Sulfonamides; D000077300:Bosentan