Nonsteroidal anti-inflammatory drugs (NSAIDs) are the most commonly used pain relievers. However, their use often threatens with serious undesirable effects, associated mainly with damage to cardiovascular system (CVS), gastrointestinal tract, kidneys and liver. Contraindications to NSAIDs prescription are clearly regulated, algorithms for their personalized appointment are determined taking into account risk factors for cardiovascular and gastrointestinal adverse events. The severity of NSAIDs side effects is mainly due to the selectivity to cyclooxygenase-2 (COX-2), as well as the physicochemical properties of various drugs. Cardiovascular adverse events differ among various NSAIDs both within commonly used drugs and among COX-2 inhibitors. It is well known that NSAIDs selective for COX-2 are safer in terms of the effect on the gastrointestinal tract than non-selective drugs. A meta-analysis showed that relatively selective COX-2 inhibitors (meloxicam, etodolac) were associated with a comparable risk of developing symptomatic ulcers and ulcers identified by endoscopy, and safety and tolerability profiles of the drugs were similar.All NSAIDs are associated with cardiovascular toxicity, however, different drugs have significant risk differences. The mechanism of NSAIDs cardiovascular adverse effects is associated with an increase of blood pressure, sodium retention, vasoconstriction, platelet activation, and prothrombotic state. It has been shown that the risk of cardiovascular adverse events when taking COX-2 inhibitors (celecoxib, etoricoxib) significantly increases. According to a study of more than 8 million people, it was found that the risk of myocardial infarction was increased in patients taking ketorolac. Further, highest to lowest risk authors list indomethacin, etoricoxib, rofecoxib (not currently used), diclofenac, a fixed combination of diclofenac with misoprostol, piroxicam, ibuprofen, naproxen, celecoxib, meloxicam, nimesulide and ketoprofen. When taking NSAIDs, the risk of heart failure decompensation increases, and it turned out to be the greatest for ketorolac, etoricoxib, and indomethacin. Meloxicam, aceclofenac, ketoprofen almost did not increase heart failure risk. It should be noted that when using the drugs (except for indomethacin and meloxicam), there is a tendency to increase the total cardiovascular and renal risks with increasing doses. Thus, it is obvious that a very careful approach is required when choosing NSAIDs. If there is an increased risk of gastrointestinal complications associated with NSAIDs, selective NSAIDs are preferred, with both coxibs and traditional selective NSAIDs showing the best safety profile in the studies. To minimize cardiovascular side effects specialists should consider the risk level of cardiovascular complications, as well as results of large clinical studies where particular NSAIDs are compared.
Представлены данные о частоте развития хронической тромбоэмболической легочной гипертензии (ХТЛГ). Описаны основные клинические проявления ХТЛГ. Освещены возможные причины и патогенетические механизмы формирования ХТЛГ, описаны маркеры неблагоприятного течения заболевания. Рассмотрены показания, результаты, ограничения к проведению хирургического лечения ХТЛГ. Приведены данные последних клинических исследований, посвященных применению бозентана, аналогов простациклина, ингибиторов фосфодиэстеразы-5 при этом тяжелом заболевании. Ключевые слова: легочная гипертензия, хроническая тромбоэмболическая легочная гипертензия, тромбоэмболия легочной артерии, тромбэндартерэктомия, бозентан, аналоги простациклина, ингибиторы фосфодиэстеразы-5. РФК 2011;7(2):199-203 Pathogenetic mechanisms and treatment principles of chronic thromboembolic pulmonary hypertension
Хроническая тромбоэмболическая легочная гипертензия (ХТЛГ) является редким жизнеугрожающим заболеванием с распространенностью 2 случая на 100000 населения. ХТЛГ-это хроническое прогрессирующее заболевание, характеризующееся высокой степенью инвалидизации и высокой смертностью у лиц молодого и среднего возраста, часто имеющее в основе генетические и аутоиммунные тромбофилические нарушения. Приводится обоснование необходимости применения патогенетической терапии орфанными препаратами, позволяющими замедлить прогрессирование заболевания.
Aim. To study the right heart remodeling and level of N-terminal brain natriuretic peptide (Nt-proBNP) in patients with chronic thromboembolic pulmonary hypertension (CTEPH). Material and methods. Patients (n=79) after pulmonary embolism were included into the study. The main group consisted of patients (n=43) with an increase in systolic pulmonary artery pressure (SPAP) >30 mm Hg: 30 (37.9%) patients had pulmonary hypertension (PH) degree I, and 13 (16.5%) -PH degree II-III. Group of comparison consisted of 36 patients expired pulmonary embolism and having SPAP <30 mm Hg. The control group consisted of 20 people. 6-minute walk test (6-MWT) and Doppler echocardiography were performed in all patients. Besides myocardial tissue Doppler echocardiography and assessment of Nt-proBNP level were performed in 38 and 71 patients, respectively. Results. Dyspnea occurred in 90.7% of patients with various degrees of PH and 80.5% of patients with normal SPAP. Patients without PH and with PH I complained of palpitations, weakness, fatigue, and dizziness with similar frequency. Patients with PH I were comparable with ones of comparison group in 6-MWT distance that dramatically decreased in patients with PH II-III. Enlargement of the right atrium (RA) and/or right ventricular (RV) was observed in 76.7% of patients with PH I and 100% of patients with PH II-III. RV diastolic function abnormalities (E/A<1 and E/A>2) were detected in 19.4%, 16.7% and 61.5% of patients of comparison group, PH I and PH II-III patients, respectively. According to myocardial tissue Doppler echocardiography Em/Am<1 was observed in 8 (72.7%) patients of the comparison group and in 13 (76.4%) patients with PH. 33.9] fmol/ml in PH I patients and 142.1 [62.1, 171.8] fmol/ml in PH II-III patients. Nt-proBNP level was 6.5 [3.1, 18.3] fmol/mL in patients of the comparison group, and it was higher than this in patients of the control group (3.5 [1.8, 7.5 fmol/ml]. Conclusion. Various indicators of heart remodeling and RV diastolic dysfunction were found in the majority of patients after pulmonary embolism, including those with normal SPAP. Elevation of Nt-proBNP level adequately reflects the severity of RV dysfunction in CTEPH patients only in PH II-III. This marker has low diagnostic value in patients without CTEPH and PH I patients.
Pulmonary hypertension (PH) can develop in different systemic autoimmune rheumatic diseases (SARD), such as systemic scleroderma (SSD), systemic lupus erythematosus, rheumatoid arthritis, and mixed connective tissue disease In most cases, patients with SARD develop WHO group I PH (pulmonary arterial hypertension associated with systemic connective tissue diseases, PAH-SCTD). General prevalence of this pathology reaches 15 cases per million adults. Most cases of PAH-SCTD are induced by SSD. Survival of PAH-SCTD patients is generally lower than survival of patients with other forms of LAH. Treatment of any SARD, including in LAH, implies a complex approach using glucocorticoids, disease-modifying anti-rheumatic drugs (cyclophosphamide, methotrexate, azathioprine, and others), and genetically engineered biologics. Specific targeted therapy is indicated for most patients with PAH-SCTD. The representative of a new class (soluble guanylate cyclase (sGC) stimulators), riociguat, has been approved for the treatment of PAH. This drug has a unique double mechanism of action: (i) sGC sensibilization to endogenous nitric oxide (NO) by stabilizing the NO-sGC bond; and (ii) direct, NO-independent sGC stimulation. For patients with PAH-SCTD, riociguat is the major alternative to phosphodiesterase-5 inhibitors both as monotherapy and combination therapy.
After suffering pulmonary embolism (PE), doctors are confronted with various consequences of the disease, from asymptomatic residual pulmonary thrombosis to the formation of chronic thromboembolic pulmonary hypertension (CTEPH). There is also a subgroup of patients who have undergone pulmonary embolism, who experience shortness of breath during physical exertion, absent before pulmonary embolism, or shortened dyspnea preceding PE, combined with residual thrombosis of pulmonary artery (PA) and normal average pressure in PA at rest during catheterization of the right heart (CRH). This condition is defined as chronic thromboembolic pulmonary disease or post thromboembolic syndrome. Pathogenetic aspects of this condition are not fully investigated. It is important to predict the development of postembolic syndrome and to develop algorithms for the diagnosis, treatment and rehabilitation of patients with symptoms and residual pulmonary thrombosis. In case of the development of pulmonary vasculopathy in some patients who have undergone pulmonary embolism, a severe life-threatening condition forms - CTEPH, characterized by an increase in pressure in the pulmonary artery, right heart failure due to the presence of organized blood clots that have entered the pulmonary vascular bed during PE. The volume of thrombotic masses does not always correlate with clinical symptoms, which indicates the importance of microvascular remodeling. If CTEPH is suspected, a diagnostic algorithm is required, including ventilation-perfusion scintigraphy, CT angiopulmonography and catheterization of the right heart. Treating a patient with CTEPH is a difficult task fora doctor. The timely referral of the patient to the center where they are involved in treatment, including surgery and CTEPH is extremely important. Timely performed thrombendarterectomy in some cases allows to completely cure the patient. In the case of inoperable CTEPH or residual pulmonary hypertension after thrombendarterectomy, balloon angioplasty of the PA is used as well as drug treatment with specific drugs that reduce the pressure in the PA (riociguat), endothelin receptor antagonists (bosentan, macitentan), prostanoids (inhalant illoprost) phosphodiesterase-5 inhibitor and combined therapy. In this article we considered some consequences directly related to PE: asymptomatic residual pulmonary thrombosis, chronic thromboembolic pulmonary disease, chronic thromboembolic pulmonary hypertension.
Цель работы-рассмотреть современные данные по применению бета-адреноблокаторов (ББ) при хронической сердечной недостаточности (ХСН). Материалы и методы. В статье рассматриваются благоприятные эффекты назначения ББ при ХСН. Продемонстрировано, что основой клинической эффективности терапии ББ при ХСН является снижение частоты сердечных сокращений. Рассмотрен вопрос о необходимости достижения целевых доз ББ при лечении больных ХСН. Показано, что назначение ББ пациентам с ХСН и сниженной фракцией выброса левого желудочка способствует увеличению насосной функции сердца, уменьшению количества госпитализаций по поводу декомпенсации сердечной недостаточности, снижению риска общей и внезапной летальности. Продемонстрированы существенные преимущества β1-селективных ББ перед неселективными в отношении их влияния на гемодинамику, метаболические процессы, реологические параметры крови и бронхи. Рассмотрена тактика назначения ББ при ХСН. Результаты. На основании данных современных исследований показана высокая эффективность и безопасность назначения β1селективных ББ больным ХСН. Заключение. Правильный выбор ББ у больных ХСН и достижение в процессе лечения снижения частоты сердечных сокращений может существенно повысить эффективность лечения.
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