Long-term efficacy of bosentan in inoperable chronic thromboembolic pulmonary hypertension

Abstract

Background. Inoperable chronic thromboembolic pulmonary hypertension (CTEPH) is associated with a poor survival. Objectives. To evaluate the long-term response to a dual endothelin receptor antagonist in patients with inoperable CTEPH. Methods. All consecutive 18 patients (mean age 63±14 years) treated with bosentan for symptomatic inoperable CTEPH were included. Efficacy was evaluated by the log value of serum levels of N-terminal-pro brain natriuretic peptide (log NTpro BNP), New York Heart Association functional class (NYHA), and the six-minute walk test (6-MWT). All follow-up data (median 31 months) were compared with baseline and divided into: short-term (<12 months), mid-term (between 12 and 24 months), and long-term follow-up (>24 months). Results. At baseline, 15 patients were in NYHA class III and three in NYHA class IV, mean log NT-pro BNP level was 7.2±1.4 log pg/ml, and mean 6-MWT distance was 404±125 m. During short-term follow-up (n=18), the NYHA class improved (p=0.001), 6-MWT distance increased by 33 m (p=0.03), and log NT-pro BNP decreased to 6.9±1.4 log pg/ml (p=0.007). During mid-term follow-up (n=17), the NYHA class improved (p<0.001), the mean 6-MWT distance increased by 41 m (p=0.01), and log NT-pro BNP was 6.9±1.4 log pg/ml (p=0.31). During late followup (n=14) the NYHA class was still improved (p=0.03), the 6-MWT distance decreased by 9 m (p=0.73), and log NT-pro BNP was 7.1±1.5 log pg/ml (p=0.91). The overall four year survival rate was 88%. Conclusion: Bosentan seems to be effective during long-term treatment in patients with inoperable CTEPH. (Neth Heart J 2009;17:329-33).

Pharmacological therapy for patients with chronic thromboembolic pulmonary hypertension

“…In a second study, 77 patients treated with bosentan for >2 years in Japan experienced significant decreases in PVR [53]. In a third study, in the Netherlands, >2 years of bosentan treatment led to stable NYHA-FC levels, but 6MWD had decreased slightly from the improved short-term value (although not to baseline levels) [52]. Finally, a report from a single centre in Japan demonstrated better long-term survival in patients with CTEPH receiving bosentan, or other "modern treatment" (bosentan, sildenafil and new oral drugs being trialled), than those taking conventional therapy for CTEPH (5-year survival 89% versus 60%, p=0.047) [63].…”

Clinical Worsening During Long-Term Follow-Up in Inoperable Chronic Thromboembolic Pulmonary Hypertension

“…The study demonstrated a positive treatment effect of bosentan on hemodynamics over placebo in this patient population during follow-up of 16 weeks [13]. Other studies report 1 year survival rates of 95% in patients with inoperable CTEPH treated with bosentan [10,12].…”

“…In addition, approximately 10% of patients who undergo PEA obtain no relief and maintain a pulmonary hypertensive state [7]. Modern specific pulmonary vasoactive medication (i.e., endothelin receptor antagonists, phosphodiesterase type 5 inhibitors, and prostacyclins) seems to improve the functional status and hemodynamics in patients with inoperable CTEPH at short-term follow-up [8][9][10][11][12][13][14][15][16][17]. However, limited data are available concerning the survival rate and time to clinical worsening in this patient population since those modern vasoactive treatments mentioned above were introduced.…”

Comparative Efficacy and Safety of Targeted Therapies for Chronic Thromboembolic Pulmonary Hypertension: A Systematic Review and Network Meta-Analysis

“…With regard to ERAs, we found that bosentan was associated with the highest probability for lowering BNP/NT-proBNP; this was the only drug that showed significant improvement in this parameter. However, retrospective research has identified that the long-term efficacy of bosentan failed to remain statistically significant in inoperable CTEPH patients [ 34 ]. Our results are based on RCTs and are not completely consistent with other published research.…”