First clinical experience with endothelin receptor antagonist bosentan used in patients with pulmonary hypertension: results of a one-year study


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AIM: To evaluate the efficiency and safety of long-term (12-month) treatment with the endothelin receptor antagonist bosentan (tracleer (Actelion, Switzerland)) in patients with pulmonary hypertension (PH)/MATERIAL AND METHODS: The prospective observational study enrolled 10 patients (8 with idiopathic PH and 2 with PH and systemic scleroderma). The patients' mean age was 50.0±6.9 years; mean pulmonary artery pressure (mPAP) 65±12 mm Hg; cardiac output (CO) 3.4±0.8 l/min; 6-minute walk test (6'WT) distance, 318±94 m. Before and 3, 6, and 12 months after the treatment, the patients underwent Doppler echocardiography, arterial blood gas analysis, external respiratory function test, and dyspnea evaluation using the MRC scale and 6'WT. The initial dose of bosentan was 62.5 mg b.i.d., then 125 mg b.i.d. following 4 weeks/RESULTS: Bosentan treatment resulted in a reduction in pulmonary artery systolic pressure and mPAP (at 12 months: 76.8±11.5 and 58.8±11.4 mm Hg, respectively; p<0.01) and an increase in CO (at 12 months: 4.2±1.2 l/min; р=0.002). Six patients were observed to have a lower WHO classification functional class (FC). Lung diffusing capacity tended to improve (at 12 months, the increment was more than 6% of the reference value; p=0.059). In the patients, dyspnea was relieved as shown by MRS scores from 3.1±0.7 (at baseline) to 2.1±0.6 (at 12 months); p=0.002. The 6'WT distance increased up to 342±67 m (at 12 months); p=0.005. The drug was well tolerated; only one patient had a transient increase in the activity of liver enzymes/CONCLUSION: The long-term bosentan treatment in patients with PH leads to improvements in pulmonary hemodynamics, WHO classification functional class, a reduction in dyspnea, and a rise in exercise tolerance.

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Первый клинический опыт применения антагониста рецепторов эндотелина бозентана у пациентов с легочной артериальной гипертензией: результаты годичного исследования. - Резюме. Цель исследования. Оценка эффективности и безопасности длительного (12 мес) лечения пациентов с легочной артериальной гипертензией (ЛАГ) антагонистом рецепторов эндотелина бозентаном (траклир, "Actelion", Швейцария). Материалы и методы. В проспективное обсервационное исследование включили 10 пациентов (8 - с идиопатической ЛАГ, 2 - с ЛАГ на фоне системной склеродермии). Средний возраст пациентов составил 50,0±6,9 года, среднее давление в легочной артерии (ДЛАср.) - 65±12 мм рт.ст., сердечный выброс (СВ) - 3,4±0,8 л/мин, расстояние, пройденное в пробе с 6-минутной ходьбой (П6-МХ), - 318±94 м. До начала лечения и через 3, 6 и 12 мес после него проводили допплероэхокардиографию, газовый анализ артериальной крови, определяли функцию внешнего дыхания, оценивали одышку по шкале MRC и П6-МХ. Начальная доза бозентана составила 62,5 мг 2 раза в сутки, затем через 4 нед - 125 мг 2 раза в сутки. Результаты. Лечение бозентаном привело к снижению СДЛА и ДЛАср. (через 12 мес: 76,8±11,5 и 58,8±11,4 мм рт.ст. соответственно; р<0,01) и повышению СВ (через 12 мес: 4,2±1,2 л/мин; р=0,002). У 6 пациентов наблюдалось снижение функционального класса (ФК) по классификации ВОЗ. Отмечена тенденция к улучшению диффузионной способности легких (к 12 мес прирост более 6% от должной; р=0,059). У больных достоверно уменьшилась одышка по шкале MRC - от 3,1±0,7 (исходно) до 2,1±0,6 (через 12 мес) балла; р=0,002. Увеличилось расстояние в П6-МХ до 342±67 м (через 12 мес); р=0,005. Препарат хорошо переносился, лишь у одного больного отмечено транзиторное повышение активности печеночных ферментов. Заключение. Длительное лечение пациентов с ЛАГ бозентаном приводит к улучшению легочной гемодинамики, ФК по классификации ВОЗ, уменьшению одышки и повышению переносимости физических нагрузок.
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