Abstract:
AIM:To evaluate the short-term efficacy of the nonselective endothelin receptor antagonist bosentan in the treatment of pulmonary hypertension (PH) associated with diffuse connective tissue diseases (CTD), as well as its effect on survival in both monotherapy and in combination with other PH-specific agents. SUBJECTS AND METHODS:The study included 20 CDT-associated PH patients who had been hospitalized in 2009-2013. All the patients had valid diagnoses of scleroderma systematica (SDS) (n = 18) or systemic lupus erythematosus (SLE) (n = 2). Bosentan was given in an initial dose of 62.5 mg/day twice for 4 weeks, then 125 mg/day twice. RESULTS:Eighteen patents completed therapy at 16 weeks. One patient with Functional Class (FC) IV PH associated with SDS died after 10 weeks of treatment because of PH progression; bosentan was discontinued in another patient following 4 weeks because of the enhanced activity of transaminases. The patients who had completed the investigation showed a significant FC decrease (from 2.9 +/- 1.0 to 2.4 +/- 1.0 following 16 weeks; p = 0.03), an increase in 6-minute walking distance (from 298 +/- 140 to 375 +/- 94 m; p < 0.002), a significant reduction in mean pulmonary artery pressure (from 48.2 +/- 15.0 to 42.8 +/- 12.0 mm Hg; p = 0.002), and pulmonary vascular resistance (PVR) (from 819 +/- 539 to 529 +/- 220 din/sec/cm(-5); p = 0.003). Right atrial pressure fell from 9.8 +/- 7.0 to 8.8 +/- 7.0 mm Hg; however, the changes were insignificant. There was a significant rise in cardiac index from 2.64 +/- 0.95 to 3.26 +/- 0.75 l/min/m2 (p = 0.005) and a significant decrease in uric acid levels from 562 +/- 254 to 469 +/- 194 micromol/l (p = 0.006). Overall 1-, 3-, and 5-year survival rates in patients with PH in the presence of CTD from PH onset were 100, 93, and 72%, respectively, in their treatment with endothelin receptor antagonists and differed significantly from the historical control group (87, 30, and 4%, respectively) when PH-specific therapy was unavailable. CONCLUSION:The survival of the bosentan-treated patients with SDS and PH becomes similar to that in the patients with classical SDS. Analysis of the findings revealed the association of survival with lower PVR at 16 weeks of bosentan therapy, which is indicative of the need for hemodynamic monitoring of therapeutic effectiveness.
journal_name
Ter Arkhjournal_title
Terapevticheskii arkhivauthors
Volkov AV,Iudkina NN,Nikolaeva EV,Kurmukov IA,Glukhova SI,Nasonov ELsubject
Has Abstractpub_date
2014-01-01 00:00:00pages
32-9issue
5eissn
0040-3660issn
2309-5342journal_volume
86pub_type
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