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BASELINE VENOUS ENDOTHELIN-1 (ET1) PLASMA LEVELS DOES NOT PREDICT CLINICAL RESPONSE TO BOSENTAN IN PULMONARY ARTERIAL HYPERTENSION FREE TO VIEW

Carmine D. Vizza, MD*; Claudio Letizia, MD; Roberto Badagliacca, MD; Susanna Sciomer, MD; Roberto Poscia, MD; Roberto Ciuffa, MD; Mariella Montano, MD; Michele D’Alto, MD; Luigi Petramala, MD; Dario Cotesta, MD; Francesco Fedele, MD
Author and Funding Information

Dept Cardio Resp Sciences Univ Rome La Sapienza, Rome, Italy


Chest


Chest. 2005;128(4_MeetingAbstracts):202S. doi:10.1378/chest.128.4_MeetingAbstracts.202S
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Abstract

PURPOSE:  ET-1 is a key mediator in the pathogenesis of pulmonary hypertension, and ET-1 venous plasma levels are a strong prognostic factor in patients with pulmonary arterial hypertension (PAH). Bosentan, a dual ETA and ETB receptor antagonist, is an effective therapy for idiopathic PAH and PAH related to connective tissue disease (CTD). The purpose of this study was to evaluate the clinical efficacy of Bosentan in relationship to baseline ET1 plasma levels in patients with PAH.

METHODS:  Twenty-four patients with PAH (idiopathic n=16, CTD n=8) in WHO functional class II-III were included in this study. All patients had a baseline venous ET1 plasma levels and were treated with oral bosentan (62.5 mg b.i.d for the first month and then 125 mg b.i.d.). Patient clinical status (WHO class), 6-minutes walking test (6MWT) and 2D-echo Doppler estimation of pulmonary artery pressure (PAPs) were assessed at baseline and at 6- month. On the basis of the median value of ET-1 plasma levels the population was divided in two groups (Gr1 <19.4 pg/ml, Gr2 >19.4 pg/ml).

RESULTS:  We did not find significant differences between the two groups’ baseline characteristics regarding gender, WHO functional class (Gr1: 2.5+0.5, Gr2: 2.8+0.5), effort capacity (6MWT distance Gr1: 427+77 meters, Gr2: 372+99 meters) and PAPs (Gr1: 85+22 mmHg, Gr2: 90+22 mmHg). After 6 months treatment both groups showed a significant improvement (ANOVA for repeated measures) in 6MWT (Gr1: +34+19 meters, Gr2: +30+21 meters) without differences between groups. WHO class had a trend towards lower class (Gr1: -0.5+0.2, Gr2: -0.4+0.2) while PAPs did not show significant changes (Gr1: -4+8 mHg, Gr2: -2+9 mmHg).

CONCLUSION:  These preliminary data suggest that the clinical efficacy of bosentan is independent to baseline venous ET1 plasma levels.

CLINICAL IMPLICATIONS:  Circulating ET1 is probably the expression of systemic neuro-hormonal activation and does not reflect the paracrine activation at pulmonary circulation. ET1 pulmonary uptake/production should be investigated further in order to clarify if there is a relationship with the clinical efficacy of bosentan.

DISCLOSURE:  Carmine Vizza, None.

2:30 PM - 4:00 PM


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