Short and long term anti-inflammatory effects of bosentan therapy in patients with pulmonary arterial hypertension: relation to clinical and hemodynamic responses.
OBJECTIVE
We sought to investigate the short- and long- term effects of bosentan therapy on endothelial, inflammatory and fibrotic markers in patients with pulmonary arterial hypertension (PAH) and the relation to clinical and hemodynamic responses.


METHODS
We studied 16 patients with moderate-severe idiopathic PAH, in WHO functional class II-IV, despite conventional treatment. Patients received additional treatment with bosentan, 62.5 mg twice daily for 1 month, followed by 125 mg twice daily for 11 months. Study endpoints included 6-min walking distance (6MWD), mean pulmonary artery pressure (mPAP), pulmonary vascular resistance (PVR) and plasma levels of intracellular cell adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule 1 (VCAM-1), IL-6 and brain natriuretic peptide (BNP). Patients were assessed at baseline, 2 months and 12 months after initiation of bosentan.


RESULTS
At 2 months there was an improvement in 6MWD (p < 0.001) and functional class (p < 0.001) and a marked fall in PVR (p < 0.001), ICAM-1 (p < 0.001), IL-6 (p < 0.001)and BNP (p = 0.001). At 12 months, 6MWD was further improved (p < 0.001), PVR remained significantly improved (p < 0.001), mPAP was significantly decreased (p < 0.001) and ICAM-1, IL-6 and BNP remained significantly lower (p < 0.001). Significant correlations were found between changes in ICAM-1 and cardiac index (r = 0.59, p = 0.01), IL-6 and PVR (r = 0.51, p = 0.04), BNP and 6MWD (r = -0.53, p = 0.03) and BNP and PAP (r = 0.51, p = 0.04) between 2- and 12-months treatment.


CONCLUSIONS
In patients with moderate-severe PAH, the addition of bosentan to therapy, exerts favorable anti-inflammatory effects, which are associated with clinical and hemodynamic improvement.
Onassis Cardiac Surgery Centre, Second Cardiology Division, Athens, Greece.
George K
GK
Karavolias
Panagiota
P
Georgiadou
Angeliki
A
Gkouziouta
Panagiotis
P
Kariofillis
Georgia
G
Karabela
Dimitrios
D
Tsiapras
Eftihia
E
Sbarouni
Antigoni
A
Chaidaroglou
Dimitrios
D
Degiannis
Stamatis
S
Adamopoulos
Vassilis
V
Voudris
D000328:Adult; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use*; D000959:Antihypertensive Agents / Q000627:therapeutic use*; D054316:Biomarkers, Pharmacological / Q000097:blood; D000077300:Bosentan; D019332:Endothelin-1 / Q000378:metabolism; D011464:Epoprostenol / Q000627:therapeutic use; D005260:Female; D006439:Hemodynamics / Q000187:drug effects*; D006801:Humans; D006976:Hypertension, Pulmonary / Q000188:drug therapy* / Q000503:physiopathology; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism / Q000502:physiology; D008297:Male; D008875:Middle Aged; D013449:Sulfonamides / Q000627:therapeutic use*; D013997:Time Factors; D016896:Treatment Outcome; D014655:Vascular Resistance / Q000187:drug effects; D055815:Young Adult
D000894:Anti-Inflammatory Agents, Non-Steroidal; D000959:Antihypertensive Agents; D054316:Biomarkers, Pharmacological; D019332:Endothelin-1; D015850:Interleukin-6; D013449:Sulfonamides; D018799:Intercellular Adhesion Molecule-1; D011464:Epoprostenol; D000077300:Bosentan