PURPOSE:Bosentan is an effective therapy for PAH. However, it is a common experience that some patients have clinical deterioration during long-term therapy. The purpose of this study was to address if clinical, hemodynamic and neurohormonal factors might predict clinical worsening in patients treated with bosentan.
METHODS:Sixty-five consecutive patients with PAH (idiopathic=45, connective tissue disease=12, congenital heart disease=8) in WHO functional class II-III were included. After initial assessment (clinical status, pulmonary hemodynamics, venous blood samples for ET-1 and BNP plasma levels), all patients were treated with oral bosentan (62.5 mg b.i.d for the first month and then 125 mg b.i.d.) and followed-up with periodical visits or phone contacts. Clinical worsening (CW) was defined as reduction in effort capacity (-20% compared to previous 6MWT), clinical deterioration requiring hospital admission, new PAH therapy, lung transplantation, death. Cox proportional hazard analysis was performed to identify the best predictors of CW.
RESULTS:The mean follow-up was 661±444 days. We observed events of CW in 32 patients. Actuarial rates of freedom from CW for the entire cohort were 76.5% at 1 year, 56.2% at 2 years, 47.3% at 3 years. Comparing patients without CW (Gr.1) with whom had CW (Gr.2), we found similar demographic, clinical and hemodynamic characteristics except for ET-1 venous plasma levels (Gr.1 12.7±6.2 pg/ml vs Gr.2 19±7.5 p<0.0006). Multivariate Cox proportional hazards model (X2 19.2; p 0.0007) identified WHO class (RR, 2.2; 95% CI, 4.8 to 1.03), ET-1 plasma levels (5 pg/ml increments; RR, 1.38; 95% CI, 1.76 to 1.08), BNP plasma level (50 pg/ml increments; RR, 1.3; 95% CI, 1.59 to 1.06) as independent significant risk factors for CW during Bosentan therapy. Klaplan Meyer plot for the population stratified for median ET-1 plasma, showed that the risk to develop CW appears after the first 6 months of bosentan therapy.
CONCLUSION:Preliminary data suggest that baseline venous BNP and ET1 plasma levels are independent prognostic factors.
CLINICAL IMPLICATIONS:The risk to develop CW appears after the first 6 months of therapy.
DISCLOSURE:Carmine Vizza, None.