Consilium MedicumConsilium MedicumConsilium MedicumConsilium Medicum2075-17532542-2170Consilium Medicum9524810.26442/20751753.2019.10.190191ArticlesСтатьиReview ArticleCARDIOTOXICITY OF NON-STEROID ANTI-INFLAMMATORY DRUGSКАРДИОТОКСИЧНОСТЬ НЕСТЕРОИДНЫХ ПРОТИВОВОСПАЛИТЕЛЬНЫХ ПРЕПАРАТОВLeonovaMarina V.ЛЕОНОВАМАРИНА ВАСИЛЬЕВНА

чл.-кор. РАЕН, д-р мед. наук, проф., член Межрегиональной общественной организации

anti23@mail.ruInterregional Public Organization “Russian Association of Clinical Pharmacologists”Межрегиональная общественная организация «Ассоциация клинических фармакологов России»151020192110VOL 21, NO10 (2019)ТОМ 21, №10 (2019)10711628122021Copyright ©; 2019, Consilium MedicumCopyright ©; 2019, ООО "Консилиум Медикум"2019Consilium MedicumООО "Консилиум Медикум"https://creativecommons.org/licenses/by-nc-sa/4.0https://consilium.orscience.ru/2075-1753/article/view/95248

Aim. To provide a scientific review on an unfavorable effect of non-steroidal anti-inflammatory drugs (NSAIDs) on cardiovascular outcomes (high blood pressure (BP), myocardial infarction, stroke, heart failure, atrial fibrillation), which can be united by the term of “cardiotoxicity”. Outcomes and methods. To write this review we searched for publications in Russian and international search engines (PubMed, eLibrary, etc.) since 1993. The review is based on an analysis of large clinical and observational studies and meta-analyzes, which is of great importance in the evidence of the data. Results. NSAIDs are widely used drugs in clinical practice. Along with the well-known gastrointestinal side effects of NSAIDs, a large group of adverse effects are cardiovascular events, which were referred to as “cardiotoxicity” in the 2000s. It was shown that cardiotoxicity of NSAIDs can be determined by the degree of selectivity to the action of cyclooxygenase (COX) -2 and has a dose-dependent and course effect for many drugs. According to a number of meta-analyzes and large clinical and observational studies (registers), the use of NSAIDs can lead to an increase in blood pressure (more than 5 mm Hg) and arterial hypertension (from 10 to 29%), and also counteracts the hypotensive effect of antihypertensive drugs ( p-blockers, angiotensin-converting enzyme inhibitors, calcium antagonists). According to large meta-analyzes, NSAIDs increase the risk of myocardial infarction, stroke, decompensated heart failure, atrial fibrillation, and mortality. These risks are showen both for selective COX-2 inhibitors - coxibs (rofecoxib, etoricoxib) and traditional non-selective NSAIDs (diclofenac, ibuprofen, indomethacin). However, celecoxib has an advantage of reducing the risk of cardiovascular outcomes over other NSAIDs. The unfavorable effect of NSAIDs on cardiovascular outcomes increases with doses or frequency of administration and is seen even with short-term use (less than 7 days), and also increases with high cardiovascular risk. Conclusions. The results of this review showes that in clinical practice there is no obvious safe therapeutic window for NSAIDs, that justifies the need for limited use of NSAIDs, especially in patients with established cardiovascular disease.

Цель - представить научный обзор о неблагоприятном влиянии препаратов класса нестероидных противовоспалительных препаратов (НПВП) на сердечно-сосудистые исходы (повышение артериального давления - АД, развитие инфаркта миокарда, инсульта, сердечной недостаточности, фибрилляции предсердий), что объединено понятием «кардиотоксичность». Материалы и методы. Для написания данного обзора был осуществлен поиск публикаций в российских и международных системах поиска (PubMed, eLibrary и проч.) с 1993 г. Обзор основан на анализе крупных клинических и наблюдательных исследований и метаанализов, что имеет большое значение в доказательности данных. Результаты. НПВП относятся к широко применяемым лекарственным препаратам в клинической практике. Наряду с хорошо известными желудочно-кишечными побочными эффектами НПВП большую группу неблагоприятных эффектов составляют осложнения со стороны сердечно-сосудистой системы, которые в 2000-е годы были объединены в «кардиотоксичность». Показано, что кардиотоксичность НПВП может определяться степенью селективности к действию на фермент циклооксигеназы (ЦОГ)-2 и имеет для многих препаратов дозозависимое и курсовое влияние. По результатам ряда метаанализов и крупных клинических и наблюдательных исследований (регистров) применение НПВП может приводить к повышению уровня АД (более 5 мм рт. ст.) и развитию артериальной гипертонии (от 10 до 29%), а также противодействовать гипотензивному эффекту антигипертензивных препаратов (p-адреноблокаторов, ингибиторов ангиотензинпревращающего фермента, антагонистов кальция). По данным крупных метаанализов НПВП повышают риск развития инфаркта миокарда, инсульта, декомпенсации сердечной недостаточности, фибрилляции предсердий, смертности. Эти риски показаны как для селективных ингибиторов ЦОГ-2 - коксибов (рофекоксиб, эторикоксиб), так и традиционных неселективных НПВП (диклофенака, ибупрофена, индометацина). Вместе с тем целекоксиб имеет преимущество в снижении риска кардиоваскулярных исходов перед другими НПВП. Неблагоприятное влияние НПВП на сердечно-сосудистые исходы увеличивается с дозами или кратностью приема и отмечается даже при краткосрочном применении (менее 7 дней), а также увеличивается при высоком сердечно-сосудистом риске. Заключение. Результаты данного обзора указывают на то, что не существует очевидного безопасного терапевтического окна для НПВП в клинической практике, что обосновывает необходимость ограниченного использования НПВП, особенно у пациентов с установленным сердечно-сосудистым заболеванием.

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