THE EFFECTIVENESS OF COMBINATION THERAPY WITH BOSENTAN AND SILDENAFIL IN PATIENTS WITH THE CLINICAL WORSENING OF IDIOPATHIC PULMONARY HYPERTENSION ON THE BACKGROUND OF SPECIFIC MONOTHERAPY

SUMMERY Objective: to evaluate the combination therapy efficacy and safety of bosentan and sildenafil in patients with idiopathic pulmonary hypertension (IPAH) in the case of clinical worsening of the underlying disease. To analyze the dynamics of clinical and functional status, the parameters of central hemodynamics and neurohumoral profile against the background of the appointment of combination of specific therapy. Material and Methods: the study included 50 patients with IPAH nonresponders functional class (FC) II-III (WHO). Patients were randomized into 2 groups of 1: 1 bosentan therapy at the starting dose of 125 mg/day titrated up to 250 mg across 4 weeks and sildenafil 60 mg/day. Of the 50 pts, 11 had marked clinical worsening IPAH to 3-10 months. Conducted 5 visits: within the framework of the initial and final visit, and the visit of clinical deterioration underwent a comprehensive examination, including right heart catheterization and research level neurohumoral status. At visit 2 in addition to test 6-minute walk surveyed the level of NT-proBNP. Results: clinical deterioration is characterized not only by deterioration FC 9% increase of the frequency of clinical symptoms and a decrease in distance in the test 6-minute walk (D6MH) by an average of 10 meters, but also an increase in systolic pulmonary artery pressure (SPAP) by 3,7 mm Hg. .st, right atrium area on 1,5 m².; increase in pulmonary vascular resistance (PVR) to 233 dyn*sec/cm^-5, slight decrease in cardiac output (CO), cardiac index (CI) and stroke volume (SV), according to right heart catheterization (RHC), as well as increase in NT-proBNP levels at 572 pg/ml, Tx B2 - 295 pg/ml, noradrenaline 128 pg/ ml and ET-1 0.4 fmol/l, a reduction of 6-keto pG F1a 82 pg/ml, adrenaline on. 18 pg/ ml, NO 13 pg/ml. Appointment of combination therapy resulted in improved clinical and functional status in the form of reduced weakness and shortness of breath, improve FC and D6MH growth by an average of 18 m., A significant decrease in SPAP by 9,5 mm Hg and PVR 336 din*sek/sm-5, some increasing CO, CI and SV, as well as the positive dynamics of indicators of neurohumoral status: NT-proBNP reduction of 400 pg/mL, Tx B2 to 432 pg/ml, norepinephrine at 115 pg/ml increase in NO metabolites level of 17 pg/ml. Appointment of combination therapy well tolerated. Conclusion: assigning specific combination therapy when the required criteria of clinical deterioration in 20% of patients with primary therapy bosentan±3 to 9 months. In 27% of patients in the group of sildenafil to 8±2 months. Combination therapy with bosentan and sildenafil for 7±2 months. from the beginning of the treatment leads to a significant improvement in functional class, a distance of 6MW test, central hemodynamic parameters; reduction of SPAP, lower NT-proBNP levels and increase levels of NO metabolites, 6-keto-PG F1 a, adrenaline. Key words: idiopathic pulmonary hypertension, bosentan, sildenafil, combination therapy.