Abstract
Current guidelines recommend use of anticoagulants (preferably fondaparinux) until hospital discharge in non-invasively treated patients (pts) with non-ST-segment elevation acute coronary syndrome (NSTEACS). however, some evidence exists that anticoagulants may be safely stopped earlier in low-risk aspirin-treated pts. Aim. To assess markers of hemostasis activation and in-hospital events rate after very early discontinuation of fondaparinux in non-invasive treatment of low-risk pts hospitalized with NSTEACS. Material and methods. 53 pts admitted with NSTEACS at median 2,3 h after last episode of chest pain were included into prospective non-comparative study. All pts had GRACE score ≤108, negative tn t (cut-off 0,03 ng/ml), and no st-segment deviation >0,1 mV. Aspirin and beta-blockers were used in all cases while clopidogrel in 35 (66,0%) only. After single subcutaneous injection of fondaparinux at presentation no anticoagulants were used. Plasma thrombin-antithrombin (tAt), d-dimer (dd), plasmin-antiplasmin (PAP) levels, plasminogen activator inhibitor-1 (PAI-1) activity and its complex with tissue plasminogen activator (tPA/PAI-1) level were measured at median 18,0 and 42,5 hours after fondaparinux. 12-lead ECG monitoring was started at median 21,2 h after fondaparinux and continued for median 38,6 h. Treadmill stress test was performed on days 4-18 (median 9) after hospitalization. Pts were followed until hospital discharge (median 14 days). Results. Plasma tAt , dd and PAP levels increased after discontinuation of fondaparinux: medians 3,1 and 3,3 ng/l (p=0,002), 359 and 486 ng/l (p=0,002), 471 and 498 ng/l (p=0,052), respectively. Increase at least one of these markers of hemostasis activation was revealed in 49 (92,5%) pts. Ischemic st-segment deviations on ambulatory ECg were found in 13 pts (24,5%). First episode appeared at median 51,8 hours after fondaparinux and only one was symptomatic. tAt , dd and PAP levels as well as their changes were not associated with recurrence of ischemia. Positive result of treadmill test was obtained in 12 Conclusion. While in non-invasive treatment of low-risk nstEACs pts very early discontinuation of fondaparinux was associated with activation of coagulation this laboratory finding was not related to recurrence of ischemia and clinical events rate was low. (25,0%) pts (5 with and 7 without ischemic st-segment deviations on ambulatory ECg; p=0,25). during hospital stay, no patient died or had myocardial infarction; 3 had recurrent angina.
Highlights
В настоящее время при неинвазивном лечении острого коронарного синдрома без стойкого подъема сегмента ST (ОКСбпST) рекомендуется достаточно длительное использование антикоагулянтов
While in non-invasive treatment of low-risk non-ST-segment elevation acute coronary syndrome (NSTEACS) pts very early discontinuation of fondaparinux was associated with activation of coagulation this laboratory finding was not related to recurrence of ischemia and clinical events rate was low
Таблица 3 Частота повышения концентрации комплексов ТАТ, PAP и D-димера в плазме крови больных с ОКСбпST и низким риском неблагоприятного течения заболевания на фоне ожидаемого заметного снижения эффекта фондапаринукса
Summary
While in non-invasive treatment of low-risk NSTEACS pts very early discontinuation of fondaparinux was associated with activation of coagulation this laboratory finding was not related to recurrence of ischemia and clinical events rate was low. Что после прекращения лечения антикоагулянтами у больных с достаточно низким риском неблагоприятного течения заболевания можно не опасаться возникновения клинически выраженного феномена отмены. При анализе объединенной базы данных исследований ESSENCE и TIMI 11B показано, что при преимущественно неинвазивном лечении ОКСбпST с использованием ацетилсалициловой кислоты, случаев смерти, инфаркта миокарда и выраженной ишемии, потребовавшей инвазивного вмешательства, в ближайшие 1,5 месяца после прекращения 2-6 дневного лечения низкомолекулярным гепарином — эноксапарином — у больных с суммой баллов по шкале оценки риска TIMI не выше 2 не отмечалось [3]. При среднем или высоком риске — сумма баллов по шкале GRACE >108 и/или депрессии сегмента ST на ЭКГ >0,1 мВ в двух и более смежных отведениях и/или уровень сердечного тропонина Т в крови >0,03 мкг/л, или выявлении других критериев невключения продолжали введение фондапаринукса вплоть до 8-х суток или более ранней выписки из стационара.
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