Efficacy and safety of sildenafil in patients with systemic scleroderma


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AIM: To retrospectively analyze the efficacy and safety of sildenafil (Sf) in patients with systemic sclerosis (SS). Subjects an/RESULTS: Sf was used in 16 patients (including 14 women) aged 20-66 years (mean 48.6±14.6 years; median 51.5 years) with SS of a duration of 2 months to 27 years (mean 8.8±7.3 years; median 6.5 years). The indications for Sf treatment were significant Raynaud's phenomenon (RP) in 3 patients, digital ulcers (DU) and/or necroses (N) in 9, pulmonary hypertension (PH) in 5 (2 patients had PH concurrent with DU/N), and critical ischemia of the left fingers in 1 patient. RP was seen in all the patients and so the effect of Sf on the course of RP was evaluated in the whole patient group/RESULTS: There was a significant decrease in the frequency and intensity of Raynaud's attacks in 11 (73%) of the 15 patients treated with Sf. This effect was obvious just in the first days of Sf treatment and remained stable throughout the treatment. No RP changes were seen in 3 patients. All 7 patients with DUs showed a decrease in their sizes just within the first two weeks of treatment. Complete DU healing was observed within 4-12 weeks of treatment. During a month, the necrotic area reduced and the signs of reparation appeared in 4 of the 6 patients. Pain ceased just within the first 5-7 days of treatment. Sf resulted in a rapid reduction in systolic pulmonary artery pressure (sPAP); in one case the latter diminished from 60 to 40 mm Hg just 90 min after the first intake of Sf 50 mg and remained unchanged during all 6 months during which the female patient was taking the drug. Doppler echocardiography showed that sPAP decreased from 103 to 85 mm Hg in another female taking Sf 100 mg for a month. The two cases showed clinical improvement as alleviated dyspnea and increased physical activity. In another case, Sf was discontinued because of dizziness after its first intake in a dose of 12.5 mg. The initial drug intake of the drug was not followed by adverse reactions in 12 (75%) of the 16 patients. Four patients had Sf-induced complaints, including headache (1), dizziness (2), and more severe angina pectoris (1). In different periods after treatment initiation, four more patients developed complications, such as fatal myocardial infarction after 6-week treatment, atrial fibrillation at 8 weeks, more severe angina at 6 months, and congestive heart failure after 5-year treatment. These complications were observed in patients with severe ECG changes, such as myocardial focal fibrosis or blood supply impairment/CONCLUSION: Sf is an effective drug to treat the manifestations of scleroderma vasculopathy, such as RP, DU/N, and PH. Sf is well tolerated in most cases. The SS patients with pronounced ECG changes have an increased risk of severe cardiac events and they need careful ECG monitoring.

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Эффективность и безопасность силденафила у больных системной склеродермией. - Резюме. Цель исследования. Ретроспективный анализ эффективности и безопасности силденафила (Сф) у больных системной склеродермией (ССД). Материалы и методы. Сф был назначен 16 больным ССД (из них 14 женщин) в возрасте 20-66 лет (в среднем 48,6±14,6 года, медиана 51,5 года) и длительностью болезни от 2 мес до 27 лет (в среднем 8,8±7,3 года, медиана 6,5 года). Показаниями к назначения Сф были выраженный синдром Рейно (СР) у 3 больных, дигитальные язвы (ДЯ) и/или некрозы у 9, легочная артериальная гипертония (ЛАГ) у 5 (у 2 больных одновременно отмечались ЛАГ и ДЯ/некрозы), критическая ишемия пальцев кисти у 1. СР имелся у всех больных и поэтому влияние Сф на течение СР оценивалось во всей группе больных.Результаты. У 11 (73%) из 15 больных во время приема Сф отмечалось значительное уменьшение частоты и интенсивности приступов Рейно. Эффект был заметным уже в первые дни приема Сф и сохранялся на протяжении всего срока лечения. У 3 больных изменений в течение СР не наблюдалось. У 7 больных с ДЯ уже в первые 2 нед лечения наблюдалось уменьшения их размеров. Полное заживление ДЯ наблюдалось в пределах 4-12 нед лечения. В течение 1 мес у 4 из 6 больных отмечались уменьшение зоны некроза и появление признаков репарации. Уже в течение первых 5-7 дней лечения отмечалось прекращение болей. Сф приводил к быстрому снижению систолического давления в легочной артерии (СДЛА); в одном случае СДЛА снизилось с 60 до 40 мм рт.ст. уже через 90 мин после первого приема 50 мг Сф и сохранялось на этом уровне все 6 мес, в течение которых больная принимала препарат. У другой больной СДЛА снизилось со 103 до 85 мм рт.ст. по данным допплероэхокардиографии через 1 мес приема 100 мг Сф. В 2 случаях наблюдалось клиническое улучшение в виде уменьшения выраженности одышки и повышения физической активности. Еще в одном случае Сф отменен из-за головокружения после первого приема 12,5 мг препарата. У 12 (75%) из 16 больных инициальный прием препарата не сопровождался побочными эффектами. Жалобы, связанные с приемом Сф, были у 4 больных, в том числе головная боль у 1, головокружение у 2 больных и усиление стенокардии - у 1 больной. Еще у 4 больных развились осложнения в разные сроки после начала лечения: острый инфаркт миокарда с летальным исходом через 6 нед приема Сф; мерцательная аритмия через 8 нед; усиление стенокардии через 6 мес; развитие застойной сердечной недостаточности через 5 лет лечения. Эти осложнения наблюдались у больных с выраженными изменениями ЭКГ, такими как очаговый фиброз или недостаточность кровоснабжения миокарда. Заключение. Сф является эффективным средством лечения таких проявлений склеродермической васкулопатии, как СР, ДЯ/некрозы и ЛАГ. Переносимость Сф в большинстве случаев хорошая. У больных ССД с выраженными изменениями ЭКГ повышен риск развития тяжелых кардиальных осложнений и в этих случаях требуется тщательный мониторинг ЭКГ.
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