Bosentan therapy for chronic thromboembolic pulmonary hypertension. A national open label study assessing the effect of Bosentan on haemodynamics, exercise capacity, quality of life, safety and tolerability in patients with chronic thromboembolic pulmonary hypertension (BOCTEPH-Study).

L Huber,U Treder

doi:10.4414/smw.2007.11819

Abstract

we performed an open-label national study to evaluate the effects of Bosentan on haemodynamics, exercise capacity, quality of life, safety and tolerability in patients with chronic thromboembolic pulmonary hypertension (CTEPH). fifteen patients with CTEPH not eligible or waiting for surgery were enrolled. The primary endpoint was the change in pulmonary vascular resistance (PVR). Secondary endpoints included quality of life (measured by the Minnesota living with heart failure questionnaire, MLHF), 6 minute walk distance (6MWD), World Health Organization (WHO) functional class, Borg dyspnoea scale, plasma endothelin, serum values of disease severity such as uric acid, N-terminal-pro brain natriuretic peptide (NTproBNP), C-reactive protein measured by a highly sensitive method (CRPs) and other serum and haemodynamic parameters. after six months of treatment with bosentan, the PVR decreased from 852 (319) to 657(249) dyn*s*m-5 (p = 0.02). Quality of life considerably improved from a mean total score of 48(14) to 35(17) (p = 0.003) with improvements in the physical (from 25(5) to 17(7)) and emotional (from 11(6) to 6(5)) subscores (p = 0.005 and 0.011), respectively. The 6MWD improved from 389(78) to 443(79) meters (p = 0.005). 4 patients (27%) improved and 11 patients (73%) maintained their WHO class with no deterioration during the six months of bosentan treatment (p = 0.02). Uric acid serum levels declined from 525(145) to 453(151) micromol/l (p = 0.006), NTproBNP and CRPs declined insignificantly. Endothelin serum levels increased from 4.3(1.5) to 5.9(2.2) pg/ml (p = 0.025). Patients tolerated the treatment well, and there were no severe adverse events or deaths. this open-label study suggests a beneficial effect of bosentan therapy not only on pulmonary haemodynamics, but also on quality of life and exercise capacity for patients with severe CTEPH.

Highlights

Consecutive patients with chronic thromboembolic pulmonary hypertension (CTEPH) either not eligible for surgery or scheduled for pulmonary endarterectomy (PEA) not earlier than 6 months and being orally anticoagulated for at least 6 months were included in this open-label, prospective study conducted under the auspices of the Swiss Society for Pulmonary Hypertension (SSPH) upon written informed consent
After obtaining written informed consent, all patients underwent a clinical assessment including the determination of World Health Organization (WHO) functional class by a standard questionnaire, completed the Minnesota living with heart failure (MLHF) questionnaire for evaluation of quality of life [1, 27], performed the 6 minute walk distance (6MWD) according to standard clinical practice with assessment of blood pressure, heart rate and oxygen saturation before and after the test, determination of the Borg dyspnoea scale immediately after the 6MWD, pulmonary function testing and right heart catheterisation for haemodynamic measures
Five patients had to be excluded due to 22 patients with CTEPH not eligible for sur- a 6MWD >500 meters, 1 patient was excluded begery within the 6 months were screened for cause of a pulmonary vascular resistance (PVR)

Summary

Study objectives: we performed an open-label national study to evaluate the effects of Bosentan on haemodynamics, exercise capacity, quality of life, safety and tolerability in patients with chronic thromboembolic pulmonary hypertension (CTEPH). Conclusion: this open-label study suggests a beneficial effect of bosentan therapy on pulmonary haemodynamics, and on quality of life and exercise capacity for patients with severe CTEPH. Case series and smaller uncontrolled studies have reported improvements in exercise capacity, markers of disease severity and pulmonary haemodynamics with the use of oral, inhaled or intravenous prostanoids, the phosphodiesterase inhibitor sildenafil and recently bosentan [10,11,12,13,14,15,16,17,18,19]. The aim of the present national open-label, non-controlled six month trial was to characterise the effects of bosentan on pulmonary haemodynamics, quality of life exercise capacity, safety and tolerability in severely ill patients with CTEPH

Patients and methods

Results

Discussion