Clinical study of the effectiveness of the sublingual liquid sildenafil of domestic production in patients with pulmonary hypertension
Keywords:pulmonary hypertension, phosphodiesterase 5 inhibitor, sildenafil
AbstractBackground. Recently, more and more world experts in the field of cardiology began to pay attention to the problem of managing patients with pulmonary hypertension (PH). According to the current recommendations, patients with PH should receive specific therapy immediately after diagnosis. One of the most studied drugs for the PH treatment is the first inhibitor of phosphodiesterase 5 — sildenafil. The purpose of this study was to prove the equivalence of the therapeutic effect of the liquid sublingual sildenafil of domestic production in patients with PH to the effect of sildenafil of import production. Materials and methods. The study included 30 stable patients with PH. The inclusion criteria were confirmed PH, which required the administration of specific therapy, and the absence of exclusion criteria. The period of observation was 6 months during which 3 visits were planned: visit 1 — screening, visit 2 — after 3 months of therapy, visit 3 — final, 6 months after the start of treatment. All patients at the beginning and at each visit underwent physical examination, with collection of complaints and history of the disease, evaluation of concomitant therapy, adherence to therapy and the presence of side effects, we measured office systolic, diastolic blood pressure and heart rate, six-minute walk test, laboratory studies of the N-terminal pro-B-type natriuretic peptide, blood thyroid-stimulating hormone level and ferritin concentration, echocardiography, cardio-ankle vascular index and ankle-brachial index. On the first visit, patients were switched to sublingual liquid form of sildenafil of domestic production. Results. The study included more women (76.7 %), mean age 39.80 ± 2.17 years, 13.3 % of patients had idiopathic PH, 3.3 % — PH associated with portal hypertension, 70 % — PH associated with congenital heart disease, 13.3 % — with chronic thromboembolic PH, on average, all had II functional class according to the World Health Organization. By the time of inclusion, 93.3 % of patients were taken tablet formulated sildenafil. The mean N-terminal pro-B-type natriuretic peptide level at the time of inclusion was 310.90 ± 66.25 pg/ml, estimated systolic pulmonary artery pressure — 89.21 ± 4.46 mmHg. After 3 and 6 months of therapy, we did not observe any reliable dynamics of office systolic, diastolic blood pressure and heart rate. After 6 months of therapy, there were no significant changes in the parameters studied, except for the ankle-brachial index, which was somewhat lowered at the beginning of the study. According to the dynamics of the six-minute walk test, no reliable dynamics was found either. After evaluating the dynamics of the echocardiography parameters, we found reliable, although relatively small, reduction of the systolic pulmonary artery pressure level by 9 mmHg (p = 0.043), as well as a significant improvement of left ventricular geometry — left ventricular eccentricity decreased by about 8 % in systole (p = 0.006). We did not observe any significant side effects of the therapy, except for minor: bad taste in the mouth after taking the drug in 2 patients, which, however, did not lead to the drug discontinuation. Conclusions. The use of the sublingual sildenafil of domestic production for six months instead of the tablet formulation of sildenafil of imported production did not cause clinical deterioration, an increase in the frequency of hospitalization, provided stable functionality against heart failure and was well tolerated by patients with PH. After six-month treatment, we have found an improvement in echocardiography parameters: a significant decrease of the estimated systolic pulmonary artery pressure by 9 mmHg (p = 0.043) and left ventricular eccentricity in systole by approximately 8 % (p = 0.006).
Наказ Міністерства охорони здоров’я України від 21.06.2016 № 614 про затвердження Уніфікованого клінічного протокола екстреної, первинної, вторинної (спеціалізованої) та третинної (високоспеціалізованої) медичної допомоги «Легенева гіпертензія у дорослих».
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