Background Among asymptomatic patients with severe carotid artery stenosis but no recent stroke or transient cerebral ischaemia, either carotid artery stenting (CAS) or carotid endarterectomy (CEA) can restore patency and reduce long-term stroke risks. However, from recent national registry data, each option causes about 1% procedural risk of disabling stroke or death. Comparison of their long-term protective effects requires large-scale randomised evidence.Methods ACST-2 is an international multicentre randomised trial of CAS versus CEA among asymptomatic patients with severe stenosis thought to require intervention, interpreted with all other relevant trials. Patients were eligible if they had severe unilateral or bilateral carotid artery stenosis and both doctor and patient agreed that a carotid procedure should be undertaken, but they were substantially uncertain which one to choose. Patients were randomly allocated to CAS or CEA and followed up at 1 month and then annually, for a mean 5 years. Procedural events were those within 30 days of the intervention. Intention-to-treat analyses are provided. Analyses including procedural hazards use tabular methods. Analyses and meta-analyses of non-procedural strokes use Kaplan-Meier and log-rank methods. The trial is registered with the ISRCTN registry, ISRCTN21144362.

Введение. Наиболее частые клинические проявления венозного тромбоэмболизма (ВТЭ) — тромбоз глубоких вен (ТГВ) и тромбоэмболия легочной артерии (ТЭЛА) — нередко осложняются рецидивом заболевания, который приводит к увеличению риска тяжелого посттромбофлебитического синдрома и/или жизнеугрожающей ТЭЛА. Роль наследственных факторов в развитии рецидива ВТЭ у лиц молодого возраста изучена недостаточно. Цель исследования: поиск генетических факторов риска рецидивирующего течения ВТЭ у пациентов молодого возраста. Материалы и методы. Обследовано 250 пациентов (117 мужчин и 133 женщины, средний возраст — 37,4 года) с ранним дебютом ВТЭ (в возрасте до 45 лет включительно). У 105 (42%) из них наблюдали рецидивирующее течение тромбоза. Всем пациентам было проведено молекулярно-генетическое исследование ДНК-полиморфизма 9 генов, вовлеченных в регуляцию активности плазменного звена гемостаза: α- и β-субъединицы фактора (F) I (Thr312Ala и –455G/A, соответственно), FII (20210 G/A), FV (1691 G/A), FXII (46 C/T), А-субъединицы FXIII (Val34Leu), ингибитора активатора плазминогена 1 типа (PAI-1, —675 4G/5G), тканевого активатора плазминогена (tPA, 311 п. н. Ins/Del) и эндотелиального рецептора протеина С (EPCR, Ser219Gly). Оценку статистической значимости различий в распределении генотипов между группами пациентов с рецидивирующим течением ВТЭ и с единственным эпизодом тромбоза в анамнезе проводили с помощью точного метода Фишера. Результаты. Рецидив ВТЭ в отдаленном периоде был выявлен у 105 (42%) пациентов. Группу сравнения составили 103 (41,2%) пациента с единственным эпизодом ВТЭ в анамнезе. У 42 (16,8%) человек наличие либо отсутствие рецидива установить не удалось. Генотип «tPA Del/Del» встречался в 2 раза реже в группе пациентов с рецидивирующим течением ВТЭ (14,3% против 28,2% у лиц с единственным эпизодом ВТЭ; ОR = 0,4; 95% CI: 0,2–0,9; p = 0,017), что указывает на его возможный протективный эффект от риска рецидива заболевания. Для остальных генов значимых различий в распределении генотипов между сравниваемыми группами не было обнаружено. Изучение «ген-генных взаимодействий» вариантов tPA и PAI-1 выявило существенные различия между группами пациентов: сочетание «tPA Del/Del + + PAI-1 4G5G» в 3,5 раза реже встречалось в группе с рецидивом венозного тромбоза (3,8% против 13,6%; OR = 0,3; 95% CI: 0,08–0,8; p = 0,011), тогда как сочетание генотипов «PAI-1 5G5G + tPA Ins/Del», напротив, было характерно, для этой группы (13,3% против 5,8% у лиц с единственным эпизодом ВТЭ; OR = 2,5; 95% CI: 0,9–6,7; p = 0,054). Заключение. Группа пациентов молодого возраста с рецидивирующим течением ВТЭ характеризуется значительным снижением частоты встречаемости генотипа tPA Del/Del, а также сочетания «tPA Del/Del + PAI-1 4G5G». Для уточнения характера влияния полиморфизма данных генов на риск развития повторных эпизодов ВТЭ необходимы дополнительные исследования. Introduction. The most frequent clinical manifestations of venous thromboembolism (VTE) — deep vein thrombosis (DVT) and pulmonary embolism (PE) are often complicated by recurrent episodes that lead to an increased risk of severe post-thrombophlebitic syndrome and/or life-threatening PE. The role of hereditary factors in the development of recurrent VTE in young people is still unclear. Aim: identifi cation of genetic risk factors for recurrent VTE in young patients. Materials and methods. We examined 250 patients (117 men and 133 women, mean age — 37.4 years) with early VTE debut (aged up to 45 years inclusive). In 105 (42%) of them, a recurring course of thrombosis was observed. In all patients a molecular genetic study of DNA polymorphism of 9 genes involved in the regulation of hemostasis plasma activity was carried out: α-and β-subunits of factor (F) I (Thr312Ala and –455 G/A, respectively), FII (20210 G/A), FV (1691 G/A), FXII (46 C/T), FXIII A subunit (Val34Leu), plasminogen activator inhibitor type I (PAI-1, —675 4G/5G), tissue plasminogen activator (tPA, 311 bp Ins/Del), and the endothelial protein C receptor (EPCR, Ser219Gly). Assessment of statistical signifi cance of diff erences in genotype distribution between the groups of patients with recurrent VTE and a single episode of thrombosis history was performed using Fisher’s exact method. Results. In the long-term period VTE recurrence was revealed in 105 (42%) patients. The comparison group consisted of 103 (41.2%) patients with a single VTE episode in the anamnesis. In 42 (16.8%) patients the presence or absence of disease recurrence was not revealed. Genotype «tPA Del Del» met 2 times less frequently in patients with recurrent VTE (14.3% vs 28.2% in individuals with a single episode of VTE; OR = 0.4; 95% CI: 0,2–0,9; p = 0.017) that indicates its possible protective effect on the risk of disease recurrence. For the remaining genes no signifi cant diff erences in genotypes distribution between the compared groups were found. Study of «gene-gene interactions» of tPA and PAI-1 variants revealed signifi cant differences between groups of patients: the combination «tPA Del/Del + PAI-1 4G5G» was 3.5 times less frequent in the group with recurrent venous thrombosis (3.8% against 13.6%; OR = 0.3; 95% CI: 0.08–0.8; p = 0.011) while the combination of the genotypes «PAI-1 5G5G + tPA Ins/Del», in contrast, was typical for this group (13.3% vs. 5.8% in individuals with a single episode of VTE; OR = 2.5; 95% CI: 0.9–6.7; p = 0.054). Conclusion. Group of young patients with recurrent VTE is characterized by a signifi cant reduction in the incidence of genotype tPA Del/Del as well as the combination of «tPA Del / Del + PAI-1 4G5G». To clarify the eff ect of polymorphism of these genes on the risk of developing of VTE recurrent episodes additional studies are needed.

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equal to 3) of 53.5%. The mean creatinine clearance value was 118.48 ml/min and the mean follow-up of these patients was 13.57 months. Results: : It has not been reported any case of Stroke, Systemic Embolism, or Major Bleeding (according to the criteria of the ISTH) during the follow-up time of the patients treated, both in the main group and in the subpopulation of patients with creatinine clearance above 95 ml/min. Only 3% of patients (17) had complications with Edoxaban, of which 12 had discontinued treatment for this cause. No case of severe or clinically relevant major bleeding has been reported according to the ISTH criteria. During the time of follow-up, twelve cases of death occurred from their base disease or from other causes, but in no case related to Edoxaban. Summary/Conclusion: This is a good sample of 552 patients and more than with a mean of 13 months of follow-up. In the analyzed subpopulation of patients with creatinine clearance greater than 95 ml/min, the good results of Edoxaban are confirmed since they have not presented any stroke recurrence or systemic embolism or major or clinically relevant hemorrhage according to the ISTH criteria. Due to the sample of 127 patients, more studies will be needed to confirm this assertion.

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