В обзоре представлены современные сведения о роли нестероидных противовоспалительных препаратов (НПВП) в развитии сердечно-сосудистых катастроф. Развитие нежелательных сердечно-сосудистых эффектов и повышение кардиоваскулярного риска при приеме НПВП большинство экспертов расценивают с точки зрения антагонистического воздействия на тромбоцитарно-сосудистый гомеостаз метаболитов циклооксигеназы – тромбоксана A2 и простагландина I2 (простациклина). Все представленные обзоры, подтверждающие увеличение риска сердечно-сосудистых осложнений при приеме НПВП, отмечают класс-специфичность данного нежелательного эффекта, неоднородную для разных представителей группы. Важным клиническим аспектом назначения НПВП пациентам с низким и умеренным кардиоваскулярным риском является анализ клинических особенностей пациента и индивидуального набора факторов риска сердечно-сосудистых заболеваний. Такие фармакокинетические характеристики НПВП, как короткий период полувыведения, высокая степень связывания с альбуминами плазмы крови, являются показателем большей безопасности НПВП, однако окончательное решение необходимо принимать на основании накопленных данных клинических исследований и мета-анализов.
The review presents current information on the role of NSAIDs in the development of cardiovascular disasters. The development of non-desirable cardiovascular effects and an increase in cardiovascular risk with the administration of NSAIDs, most experts assess in terms of the antagonistic effect on the platelet-vascular homeostasis of metabolites of COX-thromboxane A2 and prostaglandin I2 (prostacyclin). All the presented reviews confirming an increase in the risk of MI complications in the administration of NSAIDs, indicate the class-specificity of this undesirable effect, not homogeneous for different representatives of the group. Important clinical aspects of prescribing NSAIDs for patients with low and moderate cardiovascular risk are the clinical features of the patient and the individual set of risk factors for CVD. Such pharmacokinetic characteristics of NSAIDs as a short half-life, a high degree of binding to blood plasma albumins are indicative of greater safety of NSAIDs, but the final decision must be made based on the accumulated data of clinical trials and meta-analyzes.
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14. Gomez-Lumbreras A, Vives R, Giner-Soriano M, Pera H, Fradera M, Marsal JR, Morros R. Analgesic drugs and risk of ischaemic stroke in patients with ostheoartritis: a real world data case-control study. Ann Rheum Dis. 2018;77(Suppl):A1722. [European League Against Rheumatism (EULAR) Congress 2018: Abstract AB1253].
15. Trelle S, Reichenbach S, Wandel S, Hildebrand P, Tschannen B, Villiger PM, et al. Cardiovascular safety of non-steroidal anti-inflammatory drugs: network meta-analysis. BMJ. 2011(Jan 11);342:7086. doi: 10.1136/bmj.c7086
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20. Harrison P, Mumford A. Screening tests of platelet function: update on their appropriate uses for diagnostic testing. Semin Thromb Hemost. 2009;35:150-7. doi:10.1055/s-0029-1220323
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22. Bowbrick VA, Mikhailidis DP, Stansby G. Value of thromboelastography in the assessment of platelet function. Clin Appl Thromb Hemost. 2003;9:137-42. doi:10.1177/107602960300900208
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24. Bailey LA, Sistino JJ, Uber WE. Is platelet function as measured by Thrombelastograph monitoring in whole blood affected by platelet inhibitors? J Extra Corpor Technol. 2005;37:43-7.
25. de Abajo FJ, Gil MJ, Poza PG, Bryant V, Oliva B, Timoner J, García-Rodríguez LA. Risk of nonfatal acute myocardial infarction associated with nonsteroidal antiinflammatory drugs, non-narcotic analgesics and other drugs used in osteoarthritis: a nested case-control study. Pharmacoepidemiology and Drug Safety. 2014. doi: 10.1002/pds
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27. Arfè A, Scotti L, Varas-Lorenzo C, et al. Non-steroidal anti-inflammatory drugs and risk of heart failure in four European countries: nested case-control study. BMJ. 2016; p. 354-4857. doi:10.1136/bmj.i4857
28. Berg J, Fellier H, Christoph T, Grarup J, Stimmeder D. The analgesic NSAID lornoxicam inhibits cyclooxygenase (COX)-1/-2, inducible nitric oxide synthase (iNOS), and the formation of interleukin (IL)-6 in vitro. Inflamm Res. 1999;48(7):369-79. doi:10.1007/s000110050474
29. Bjordal JM, Klovning A, Ljunggren AE, et al. Short-term efficacy of pharmacotherapeutic interventions in osteoarthritic knee pain: a meta-analysis of randomised placebo-controlled trials. Eur J Pain. 2007;11:125-38. doi: 10.1016/j.ejpain.2006.02.013
30. Kullich W, Klein G. Influence of the nonsteroidal antiinflammatory drug lornoxicami. v. on the secretion of the endogenous opiate peptides dynorphin and β-endorphin. Aktuel Rheumatol. 1992;17(4):128-32. doi:10.1055/s-2008-1047362
31. Radhofer-Welte S, Rabasseda X. Lornoxicam, a new potent NSAID with an improved tolerability profile. Drugs Today (Barc). 2000;36(1):55-76. doi:10.1358/dot.2000.36.1.566627
32. Parada L, Marstein JP, Danilov A. Tolerability of the COX-1/COX-2 inhibitor lornoxicam in the treatment of acute and rheumatic pain. Pain Manag. 2016 Oct;6(5):445-54. doi:10.2217/pmt.16.7
________________________________________________
1. Golubev VL, Danilov AB, Vane AM. Psychosocial factors, gender and pain. J Neurology and Psychiatry named after SS Korsakov. 2004;104(11):70-3 (In Russ.)
2. Nijs J, Malfliet A, Ickmans K. Treatment of central sensitization in patients with «unexplained» chronic pain: an update Expert. Opin Pharmacother. 2014;15(12):1671-83.
3. Smith SR, Deshpande BR, Collins JE, et al. Comparative pain reduction of oral non-steroidal anti-inflammatory drugs and opioids for knee osteoarthritis: systematic analytic review. Osteoarthritis Cartilage. 2016;24(6):962-72. doi: 10.1016/j.joca.2016.01.135
4. Gargallo CJ, Sostres C, Lanas А. Prevention and Treatment of NSAID Gastropathy. A. Curr Treat Options Gastro. 2014;12:398. doi:10.1007/s119 38-014-0029-4
5. Amer M, Bead VR, Bathon J, Blumenthal RS, Edwards DN. Use of nonsteroidal anti-inflammatory drugs in patients with cardiovascular disease: a cautionary tale. Cardiology in Review. 2010;18(4):204-12. doi: 10.1097/crd.0b013e3181ce1521
6. Насонов Е.Л., Лабезник Л.Б., Беленков Ю.Н. Применение нестероидных противовоспалительных препаратов. Клинические рекомендации. М.: Алмаз, 2006 [Nasonov EL, Labeznik LB, Belenkov YuN. Use of nonsteroid anti-inflammatory medicines. Clinical recommendations. M.: Diamond, 2006 (In Russ.)].
7. Karatev AE. A possibility of use of NPVP at patients with a GIT and cardiovascular risk factors. RMZh. 2009;17(7):495-503 (In Russ.)
8. Warner TD, Mitchel JA. Cycloxygenase; new isoforms, new inhibitors, and new lessons from clinic. FASEB J. 2004;18:790-804. doi:10.1096/fj.03-0645rev
9. Solomon SD, et al. for the Adenoma Prevention with Celecoxib (APC) Study Investigators. Cardiovascular risk associated with celecoxib in a clinical trial for colorectal adenoma prevention. N Engl J Med. 2005;352:1071-80. doi: 10.1097/01.aog.0000166692.14982.d1
10. Elliot M. Antman AH. A Scientific Statements Use of Nosteroidal Antiflammotory Drugs. Circulation. 2007;115:1634-42.
11. Lanas A, Tornero J, Zamorano JL. Assessment of gastrointestinal and cardiovascular risk in patients with osteoarthritis who require NSAIDs: the LOGICA study. Ann Rheum Dis. 2010 Aug;69(8):1453-8. doi: 10.1136/ ard.2009.123166
12. Maillard M, Burnier M. Comparative cardiovascular safety of traditional nonsteroidal anti-inflammatory drugs. Expert Opin Drug Saf. 2006;5:83-94. doi: 10.1517/14740338.5.1.83
13. Atiquzzaman M, Kopec J, Karim ME, Wong H, Anis A. The role of nsaids in the association between osteoarthritis and cardiovascular diseases: a population-based cohort study. Ann Rheum Dis. 2018;77(Suppl):A144. [European League Against Rheumatism (EULAR) Congress 2018: Abstract OP0190].
14. Gomez-Lumbreras A, Vives R, Giner-Soriano M, Pera H, Fradera M, Marsal JR, Morros R. Analgesic drugs and risk of ischaemic stroke in patients with ostheoartritis: a real world data case-control study. Ann Rheum Dis. 2018;77(Suppl):A1722. [European League Against Rheumatism (EULAR) Congress 2018: Abstract AB1253].
15. Trelle S, Reichenbach S, Wandel S, Hildebrand P, Tschannen B, Villiger PM, et al. Cardiovascular safety of non-steroidal anti-inflammatory drugs: network meta-analysis. BMJ. 2011(Jan 11);342:7086. doi: 10.1136/bmj.c7086
16. Karateev AE, Nasonov EL, Yakhno NN, et al. Clinical recommendations "Rational use of nonsteroid anti-inflammatory medicines (NPVP) in clinical practice". Modern rheumatology. 2015;(1):4-23 (In Russ.)
17. Oganov RG, Denisov IN, Simanenkov VI, et al. Comorbid pathology in clinical practice. Clinical recommendations. Cardiovascular therapy and prevention. 2017;16(6):5-56 (In Russ.) doi:10.15829/1728-8800-2017-6-5-56
18. Food and Drug Administration [Internet]. Silver Spring, MD. FDA Briefing Information for the February 10-11, 2014 Joint Meeting of the Arthritis Advisory Committee and Drug Safety and Risk Management Advisory Committee.
19. Drug Safety Update. 2013 June;6(11):A2.
20. Harrison P, Mumford A. Screening tests of platelet function: update on their appropriate uses for diagnostic testing. Semin Thromb Hemost. 2009;35:150-7. doi:10.1055/s-0029-1220323
21. Tantry US, Bliden KP, Gurbel PA. Overestimation of platelet aspirin resistance detection by thrombelastograph platelet mapping and validation by conventional aggregometry using arachidonic acid stimulation. J Am Coll Cardiol. 2005;46:1705-9. doi:10.1016/j.jacc.2005.05.090
22. Bowbrick VA, Mikhailidis DP, Stansby G. Value of thromboelastography in the assessment of platelet function. Clin Appl Thromb Hemost. 2003;9:137-42. doi:10.1177/107602960300900208
23. Craft RM, Chavez JJ, Bresee SJ, et al. A novel modification of the Thrombelastograph assay, isolating platelet function, correlates with optical platelet aggregation. J Lab Clin Med. 2004;143:301-9. doi:10.1016/j.lab.20 04.01.011
24. Bailey LA, Sistino JJ, Uber WE. Is platelet function as measured by Thrombelastograph monitoring in whole blood affected by platelet inhibitors? J Extra Corpor Technol. 2005;37:43-7.
25. de Abajo FJ, Gil MJ, Poza PG, Bryant V, Oliva B, Timoner J, García-Rodríguez LA. Risk of nonfatal acute myocardial infarction associated with nonsteroidal antiinflammatory drugs, non-narcotic analgesics and other drugs used in osteoarthritis: a nested case-control study. Pharmacoepidemiology and Drug Safety. 2014. doi: 10.1002/pds
26. Lúcio SM, Ferreira H, Lima J, Reis S. Interactions between Oxicams and Membrane Bilayers: an Explanation for Their Different COX. Medicinal Chemistry. 2006;2:447-56. doi:2174/157340606778250199
27. Arfè A, Scotti L, Varas-Lorenzo C, et al. Non-steroidal anti-inflammatory drugs and risk of heart failure in four European countries: nested case-control study. BMJ. 2016; p. 354-4857. doi:10.1136/bmj.i4857
28. Berg J, Fellier H, Christoph T, Grarup J, Stimmeder D. The analgesic NSAID lornoxicam inhibits cyclooxygenase (COX)-1/-2, inducible nitric oxide synthase (iNOS), and the formation of interleukin (IL)-6 in vitro. Inflamm Res. 1999;48(7):369-79. doi:10.1007/s000110050474
29. Bjordal JM, Klovning A, Ljunggren AE, et al. Short-term efficacy of pharmacotherapeutic interventions in osteoarthritic knee pain: a meta-analysis of randomised placebo-controlled trials. Eur J Pain. 2007;11:125-38. doi: 10.1016/j.ejpain.2006.02.013
30. Kullich W, Klein G. Influence of the nonsteroidal antiinflammatory drug lornoxicami. v. on the secretion of the endogenous opiate peptides dynorphin and β-endorphin. Aktuel Rheumatol. 1992;17(4):128-32. doi:10.1055/s-2008-1047362
31. Radhofer-Welte S, Rabasseda X. Lornoxicam, a new potent NSAID with an improved tolerability profile. Drugs Today (Barc). 2000;36(1):55-76. doi:10.1358/dot.2000.36.1.566627
32. Parada L, Marstein JP, Danilov A. Tolerability of the COX-1/COX-2 inhibitor lornoxicam in the treatment of acute and rheumatic pain. Pain Manag. 2016 Oct;6(5):445-54. doi:10.2217/pmt.16.7
Авторы
А.В. Наумов, О.Н. Ткачева, Н.О. Ховасова
ФГБОУ ВО «Российский национальный исследовательский медицинский университет им. Н.И. Пирогова» Минздрава России, кафедра болезней старения ФДПО. Обособленное структурное подразделение «Российский геронтологический научно-клинический центр», Москва, Россия
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A.V. Naumov, O.N. Tkacheva, N.O. Khovasova
N.I. Pirogov Russian National Research Medical University of the Ministry of Health of the Russian Federation, Department of diseases of aging. Russian clinical investigator center of gerontologies, Moscow, Russia