Автореферат и диссертация по медицине (14.00.06) на тему:Клинико-патогенетическое аспекты лечения острого коронарного синдрома без подъема сегмента ST: дифференцированная антитромбиновая терапия и раннее применение статина

СПИСОК СОКРАЩЕНИЙ.

ВВЕДЕНИЕ.

ГЛАВА 1. ПРОБЛЕМА ОСТРОГО КОРОНАРНОГО СИНДРОМА БЕЗ

ПОДЪЕМА СЕГМЕНТА ST. ОБЗОР ЛИТЕРАТУРЫ.

1.1. Современное представление о патогенезе ОКС без подъема сегмента ST.

1.2. Стратификация риска острого коронарного тромбоза.

1.3. Антитромбоцитарная терапия: ацетилсалициловая кислота.

1.4. Антитромбины.

1.5. Нефракционированный гепарин, общий механизм действия и фармакологические свойства.

1.5.1. Нефракционированный гепарин при острых коронарных синдромах без подъема сегмента ST.

1.5.2. Недостатки нефракционированного гепарина.

1.5.3. Безопасность применения нефракционированного гепарина при ОКС без подъема сегмента ST.

1.5.4. Уровень гипокоагуляции и его связь с развитием неблагоприятных событий.

1.5.5. Гепарининдуцированная тромбоцитопения.

1.6. Низкомолекулярные гепарины, общий механизм действия и фармакологические свойства.

1.6.1. Эффективность применения низкомолекулярных гепаринов при ОКС без подъема сегмента ST.

1.6.2. Равноценны ли низкомолекулярные гепарины?.

1.6.3. Какой низкомолекулярный гепарин имеет преимущества в лечении ОКС без подъема сегмента ST?.

1.6.4. Сколько времени нужно лечить гепарином ОКС без подъема сегмента ST?.

1.6.5. Безопасность применения низкомолекулярных гепаринов при ОКС без подъема сегмента ST.

1.6.6. Проблема выбора антитромбина в раннем лечении ОКС без подъема сегмента ST.

1.7. Оральные антикоагулянты: общий механизм действия и фармакологические свойства.

1.7.1. Противопоказания, недостатки и осложнения применения оральных антикоагулянтов.

1.7.2. Лабораторный контроль и оптимизация доз оральных антикоагулянтов.

1.7.3. Оральные антикоагулянты в лечении ОКС.

1.8. Статины: обоснование назначения статинов, механизм действия статинов.

1.8.1. Статины в лечении ишемической болезни сердца.

1.8.2. Статины в лечении ОКС.

ГЛАВА 2. МАТЕРИАЛ И МЕТОДЫ ИССЛЕДОВАНИЯ.

2.1. Объект исследования.

2.2. Методы исследования.

2.2.1. Методы исследования тромбоцитарно-сосудистого гемостаза.

2.2.2. Методы исследования коагуляционного гемостаза.

2.2.3. Определение первичных физиологических антикоагулянтов.

2.2.4. Определение маркеров внутрисосудистого свертывания и фибринолиза.

2.2.5. Определение провоспалительных маркеров.

2.2.6. Определение активности ферментов.

2.2.7. Определение маркеров некроза миокарда.

2.2.8. Реологические характеристики крови.

2.2.9. Определение показателей липидного спектра.

2.2.10. Селективная коронарография и левая вентрикулография.

2.2.11. Исследование функционального состояния эндотелия периферических артерий.

2.2.12. Статистическая обработка результатов.

ГЛАВА 3. КЛИНИЧЕСКАЯ ЭФФЕКТИВНОСТЬ

ПРОТИВОТРОМБОТИЧЕСКОЙ ТЕРАПИИ У БОЛЬНЫХ С ОКС БЕЗ ПОДЪЕМА СЕГМЕНТА ST (РЕЗУЛЬТАТЫ ИССЛЕДОВАНИЯ).

3.1. Сравнение эффективности двух способов введения нефракциони-рованного гепарина у больных с ОКС без подъема сегмента ST.

3.1.1. Длительность гепаринотерапии в исследованных группах.

3.1.2. Сравнительная оценка «конечных точек».

3.1.3. Ассоциация терапевтического уровня АЧТВ со способом введения нефракционированного гепарина.

3.1.4. Способ подбора оптимальной дозы нефракционированного гепарина при подкожном введении у больных с острым коронарным синдромом без подъема сегмента ST.

3.1.5. Сравнительная оценка «конечных точек» у больных с терапевтическим уровнем АЧТВ при лечении нефракционированным гепарином.

3.2. Сравнение эффективности дальтепарина и внутривенной инфузии нефракционированного гепарина у больных с ОКС без подъема сегмента ST.

3.3. Сравнение эффективности эноксапарина и внутривенной инфузии нефракционированного гепарина у больных с ОКС без подъема сегмента ST.

3.4. Сравнение эффективности надропарина и внутривенной инфузии нефракционированного гепарина у больных с ОКС без подъема сегмента ST.

3.5. Сравнение эффективности антитромбинов и сочетания их с оральным антикоагулянтом у больных с ОКС без подъема сегмента ST.

3.5.1. Сравнение эффективности нефракционированного гепарина и сочетания его с фенилином.

3.5.2. Сравнение эффективности дальтепарина и сочетания его с фенилином.

3.5.3. Сравнение эффективности сочетания дальтепарина с фенилином и нефракционированного гепарина с фенилином.

3.5.4. Сравнение эффективности надропарина и сочетания его с фенилином.

3.5.5. Сравнение эффективности эноксапарина и сочетания его с фенилином.

3.6. Клинический пример.

ГЛАВА 4. СОСТОЯНИЕ СИСТЕМЫ ПЛАЗМЕННОГО И

ТРОМБОЦИТАРНОГО ГЕМОСТАЗА В УСЛОВИЯХ ПРОВЕДЕНИЯ ПРОТИВОТРОМБОТИЧЕСКОЙ ТЕРАПИИ У БОЛЬНЫХ С ОКС БЕЗ ПОДЪЕМА СЕГМЕНТА ST (РЕЗУЛЬТАТЫ ИССЛЕДОВАНИЯ).

4.1. Состояние системы гемостаза и активность сывороточных ферментов у больных ОКС без подъема сегмента ST в условиях проведения антитромбиновой терапии.

4.2. Особенности реакции системы плазменного гемостаза и сывороточных ферментов в зависимости от вида антитромбиновой терапии.

4.3. Состояние тромбоцитарного гемостаза у больных с ОКС без подъема сегмента ST в условиях проведения антитромбиновой терапии.

ГЛАВА 5. РАННЕЕ ПРИМЕНЕНИЕ СИМВАСТАТИНА В ЛЕЧЕНИИ ОКС БЕЗ ПОДЪЕМА СЕГМЕНТА ST (РЕЗУЛЬТАТЫ ИССЛЕДОВАНИЯ).

5.1. Сравнение эффективности надропарина и сочетания его с симвастатином у больных с ОКС без подъема сегмента ST.

5.2. Влияние раннего назначения симвастатина на показатели гемостаза.

5.3. Влияние раннего назначения симвастатина на липиды крови.

5.4. Влияние раннего назначения симвастатина на маркеры воспаления.

5.4.1. Динамика уровня серомукоидов.

5.4.2. Динамика уровня С-реактивного белка.

5.4.3. Динамика уровня цитокинов.

5.5. Влияние раннего назначения симвастатина на функциональное состояние эндотелия сосудов у больных с ОКС без подъема сегмента ST.

5.6. Оценка безопасности изучаемых препаратов.

5.6.1. Сравнительная оценка геморрагических осложнений.

5.6.2. Влияние на функцию тромбоцитов.

5.7. Клинические примеры.

5.7.1. Клинический пример 1.

5.7.2. Клинический пример 2.

ГЛАВА 6. ВЗАИМОСВЯЗЬ ХАРАКТЕРА ВОЗДЕЙСТВИЯ НА СИСТЕМУ

ГЕМОСТАЗА АНТИТРОМБИНОВЫХ ПРЕПАРАТОВ И ИХ КЛИНИЧЕСКОЙ ЭФФЕКТИВНОСТИ У ПАЦИЕНТОВ С ОКС БЕЗ

ПОДЪЕМА СЕГМЕНТА ST.

6.1. Анализ взаимосвязи между частотой возникновения неблагоприятных коронарных событий и показателями гемостаза при проведении противотромботической терапии.

6.2. Использование математического моделирования для дифференцированного назначения противотромботическоЙ терапии больным с ОКС без подъема сегмента ST.

6.2.1. Математическая модель для дифференцированного назначения гепаринов в зависимости от рассчитанного риска падения активности антитромбина III.

6.2.2. Математическая модель для определения необходимости назначения оральных антикоагулянтов в зависимости от рассчитанного риска повышения концентрации РФМК после отмены гепарина.

ГЛАВА 7. ОБСУЖДЕНИЕ РЕЗУЛЬТАТОВ.

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