ЭФФЕКТИВНОСТЬ И БЕЗОПАСНОСТЬ ТЕРАПИИ БЕТА-АДРЕНОБЛОКАТОРАМИ В ПЕРИОПЕРАЦИОННОМ ПЕРИОДЕ ВНЕСЕРДЕЧНЫХ ХИРУРГИЧЕСКИХ ВМЕШАТЕЛЬСТВ — СМЕНА ПАРАДИГМЫ?

Долгое время бета-блокаторы (ББ) были бесспорно лидирующим классом препаратов, назначаемых с целью профилактики инфаркта миокарда (ИМ) и сердечно-сосудистой смертности в интра- и раннем послеоперационном периодах внесердечных хирургических вмешательств. Однако в последние годы результаты наиболее крупных исследований семейства DECREASE, указывающие на положительное влияние ББ в плане снижения частоты развития периоперационного инфаркта миокарда, были дискредитированы. В обзоре обсуждаются современные представления о патогенезе периоперационного инфаркта миокарда, анализируются работы, в которых изучались различные аспекты применения ББ в периоперационном периоде. Показано, что их краткосрочное действие сводится к подавлению стрессовых реакций сердечно-сосудистой системы, а отдаленные эффекты связаны со снижением уровня медиаторов воспаления, что приводит к стабилизации атеросклеротических бляшек в коронарных артериях, уменьшению их объема. Вместе с тем, на сегодняшний день мы не располагаем убедительными данными относительно пользы и рисков периоперацинной терапии ББ, и вопрос об эффективности и безопасности назначения ББ при выполнении внесердечных хирургических вмешательств остается открытым. Для ответа на него требуется проведение новых хорошо спланированных рандомизированных исследований с обоснованным выбором конкретного препарата, соблюдением режима дозирования и сроков терапии, титрацией дозы ББ, строгим контролем целевой частоты сердечных сокращений и артериального давления и жесткими конечными точками.

1. Palda V, Detsky A. Perioperative assessment and management of risk from coronary artery disease. Ann Intern Med 1997; 127:313-28.

2. Mangano D, Layug E, Wallace A, et al. Effect of atenolol on mortality and cardiovascular morbidity after noncardiac surgery. Multicenter Study of Perioperative Ischemia Research Group. N Engl J Med 1996; 335:1713-20.

3. Poldermans D, Boersma E, Bax J, et al. The effect of bisoprolol on perioperative mortality and myocardial infarction in high-risk patients undergoing vascular surgery. Dutch Echocardiographic Cardiac Risk Evaluation Applying Stress Echocardiography Study Group. N Engl J Med 1999; 341:1789-94.

4. Zaugg M, Bestmann L, Wacker J, et al. Adrenergic receptor genotype but not perioperative bisoprolol therapy may determine cardiovascular outcome in at-risk patients undergoing surgery with spinal block: the Swiss Beta Blocker in Spinal Anesthesia (BBSA) study: a double-blinded, placebo-controlled, multicenter trial with 1-year follow-up. Anesthesiology 2007; 107: 33-44.

5. Dunkelgrun M, Boersma E, Schouten O, et al. Bisoprolol and fluvastatin for the reduction of perioperative cardiac mortality and myocardial infarction in intermediate-risk patients undergoing noncardiovascular surgery: a randomized controlled trial (DECREASE-IV). Ann Surg 2009; 249:921-6.

6. Devereaux P, Yang H, Yusuf S, et al. Effects of extended-release metoprolol succinate in patients undergoing non-cardiac surgery (POISE trial): a randomised controlled trial. Lancet 2008; 371:1839-47.

7. Wallace A, Layug B, Tateo I, et al. Prophylactic atenolol reduces postoperative myocardial ischemia. McSPI Research Group. Anesthesiology 1998; 88:7-17.

8. Brady A, Gibbs J, Greenhalgh R, et al. Perioperative beta-blockade (POBBLE) for patients undergoing infra- renal vascular surgery: results of a randomized double-blind controlled trial. J Vasc Surg 2005; 41:602-9.

9. Juul A, Wetterslev J, Gluud C, et al. Effect of perioperative beta blockade in patients with diabetes undergoing major non-cardiac surgery: randomised placebo controlled, blinded multicentre trial. Br Med J 2006; 332: 1482.

10. Yang H, Raymer K, Butler R, et al. The effects of perioperative beta-blockade: results of the Metoprolol after Vascular Surgery (MaVS) study, a randomized controlled trial. Am Heart J 2006; 152:983-90.

11. Eagle K, Berger P, Calkins H, et al. ACC/AHA guideline update for perioperative cardiovascular evaluation for noncardiac surgery — executive summary: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee to Update the 1996 Guidelines on Perioperative Cardiovascular Evaluation for Noncardiac Surgery). J Am Coll Cardiol 2002; 39:542-653.

12. Eagle K, Brundage B, Chaitman B, et al. Guidelines for perioperative cardiovascular evaluation for noncardiac surgery: report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee on Perioperative Cardiovascular Evaluation for Noncardiac Surgery) Circulation 1996; 93:1278-317.

13. Fleisher L, Beckman J, Brown K, et al. ACC/AHA 2006 guideline update on perioperative cardiovascular evaluation for noncardiac surgery: focused update on perioperative beta-blocker therapy: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Update the 2002 Guidelines on Perioperative Cardiovascular Evaluation for Noncardiac Surgery): developed in collaboration with the American Society of Echocardiography, American Society of Nuclear Cardiology, Heart Rhythm Society, Society of Cardiovascular Anesthesiologists, Society for Cardiovascular Angiography and Interventions, and Society for Vascular Medicine and Biology. Circulation 2006; 113:2662-74.

14. Fleisher L, Beckman J, Brown K, et al. 2009 ACCF/AHA focused update on perioperative beta blockade incorporated into the ACC/AHA 2007 guidelines on perioperative cardiovascular evaluation and care for noncardiac surgery: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. Circulation 2009; 120:169-276.

15. Lindenauer P, Pekow P, Wang K, et al. Perioperative Beta-Blocker Therapy and Mortality after Major Noncardiac Surgery. N Engl J Med 2005; 353: 349-61.

16. Poldermans D, Bax J, Boersma E, et al. Guidelines for pre- operative cardiac risk assessment and perioperative cardiac man- agement in non-cardiac surgery: the task force for preoperative cardiac risk assessment and perioperative cardiac management in non-cardiac surgery of the European Society of Cardiology (ESC) and endorsed by the European Society of Anaesthesiology (ESA). Eur J Anaesthesiol 2010; 27:92-137.

17. Shchukin JuV, Hohlunov SM, Surkova EA, et al. Prognosis and prevention of cardiac complications in noncardiac surgery. National guidelines of Russian society of cardiology. Cardiovascular Therapy and Prevention 2011; 10 (6): 1-28. Russian (Ю. В. Щукин, С.М. Хохлунов, Е. А. Суркова и др. Прогнозирование и профилактика кардиальных осложнений внесердечных хирургических вмешательств. Национальные рекомен¬дации ВНОК. Кардиоваскулярная терапия и профилактика 2011; 10 (6):1-28).

18. Flynn B, Vernick W, Ellis J, et al. b-Blockade in the perioperative management of the patient with cardiac disease undergoing non-cardiac surgery. J Anaesthesia 2011; 107 (S1): i3-i15.

19. Notice of Concern. J Am Coll Cardiol 2012; 60:2696-7.

20. Wise J. Extent of Durch psychologist's trial fraud was unprecendented. BMJ 2011; 343:969.

21. O'Riordan M, Erasmus MC fires Poldermans; ESC reviews his work. www.theheart.org/ article/1315171.do (27 February 2013).

22. Poldermans D, Bax J, Schouten O, et al. Should major vascular surgery be delayed because of preoperative cardiac testing in intermediate-risk patients receiving beta- blocker therapy with tight heart rate control? J Am Coll Cardiol 2006; 48:964-969.

23. Poldermans D, Schouten O, Benner R, et al. Fluvastatin XL use is associated with improved cardiac outcome after major vascular surgery. Results from a randomized placebo controlled trial: DECREASE III. Circulation 2008; 118: S792.

24. Feringa H, Elhendy A, Bax J, et al. Baseline plasma N-terminal pro-B-type natriuretic peptide is associated with the extent of stress-induced myocardial ischemia during dobutamine stress echocardiography. Coron Artery Dis 2006; 17:255-9.

25. Feringa H, Bax J, Elhendy A, et al. Association of plasma N-terminal pro-B-type natriuretic peptide with postoperative cardiac events in patients undergoing surgery for abdominal aortic aneurysm or leg bypass. Am J Cardiol 2006; 98:111-115.

26. Ldscher T. The codex of science: honesty, precision, and truth — and its violations. European Heart Journal 2013; 34:1018-23.

27. Don Poldermans MD PhD, replies to European Heart Journal Editorial European Heart Journal. European Heart Journal 2013; 34:1698.

28. Bouri S, Shun-Shin M, Cole G., et al. Meta-analysis of secure randomized controlled trials of beta-blockade to prevent perioperative death in noncardiac surgery. Heart 2013; DOI: 10.1136/heartjnl-2013-304262.

29. Yang X-Y Wu X-M, Wang S, et al. Effects of metoprolol on perioperative cardiovascular events in patients with risk or at high risk for coronary artery disease undergoing non- cardiac surgery. Zhonghua Yi Xue Za Zhi 2008; 88:1476-80.

30. Neary W, McCrirrick A, Foy C, et al. Lessons learned from a randomised controlled study of perioperative beta blockade in high risk patients undergoing emergency surgery. The Surgeon 2006; 4:139-43.

31. Bayliff C, Massel D, Inculet R, et al. Propranolol for the prevention of postoperative arrhythmias in general thoracic surgery. Ann Thorac Surg 1999; 67:182-6.

32. Chen Z, Jiang L, Chen Y, et al. Addition of clopidogrel to aspirin in 45,852 patients with acute myocardial infarction: randemised placebo-controlled trial. Lancet 2005; 366:1607-21.

33. Ellenberger C, Tait G., Beattie W. Chronic beta blockade is associated with a better outcome after elective noncardiac surgery than acute beta blockade: a single-centre propensity- matched cohort study. Anesthesiology 2011; 114:817-23.

34. Wallace A, Au S, Cason B. Association of the pattern of use of perioperative beta-blockade and postoperative mortality. Anesthesiology 2010; 113:794-805.

35. Van Klei W, Bryson G, Yang H, et al. Effect of beta-blocker prescription on the incidence of postoperative myocardial infarction after hip and knee arthroplasty. Anesthesiology 2009; 111:717-24.

36. Badgett R., Lawrence V, Cohn S. Variations in pharmacology of beta-blockers may contribute to heterogeneous results in trials of perioperative beta-blockade. Anesthesiology 2010; 113:585-92.

37. Shin J, Johnson J. Pharmacogenetics of beta-blockers. Pharmacotherapy 2007; 27:874-87.

38. Phillips K, Veenstra D, Oren E, et al. Potential role of pharmacogenomics in reducing adverse drug reactions: A systematic review. JAMA 2001; 286:2270-9.

39. Fux R, Morike K, Prohmer A, et al. Impact of CYP2D6 genotype on adverse effects during treatment with metoprolol: A prospective clinical study. Clin Pharmacol Ther 2005; 78:378-87.

40. Baker J. The selectivity of beta-adrenoceptor antagonists at the human beta1, beta2 and beta3 adrenoceptors. Br J Pharmacol 2005; 144:317-22.

41. Ragoonanan T, Beattie W, Mazer C, et al. Metoprolol reduces cerebral tissue oxygen tension after acute hemodilution in rats. Anesthesiology 2009; 111:988-1000.

42. Beattie W, Wijeysundera D, Karkouti K, et al. Acute surgical anemia influences the cardioprotective effects of B-blockade: A single-center, propensity-matched cohort study. Anesthesiology 2010; 112:25-33.

43. Priebe H. Perioperative myocardial infarction — etiology and prevention. Br J Anaesth 2005; 95:3-19.

44. Priebe H. Triggers of perioperative myocardial ischaemia and infarction. Br J Anaesth 2004; 93:9-20.

45. Sametz W, Metzler H, Gries M, et al. Perioperative catecholamine changes in cardiac risk patients. Eur J Clin Invest 1999; 29:582-7.

46. Raby K, Brull S, Timimi F., et al. The effect of heart rate control on myocardial ischemia among high-risk patients after vascular surgery. Anesth Analg 1999; 88:477-82.

47. Landesberg G. The pathophysiology of perioperative myocardial infarction: facts and perspectives. J Cardiothorac Vasc Anesth 2003; 17:90-100.

48. Landesberg G, Mosseri M, Zahger D, et al. Myocardial infarction after vascular surgery: the role of prolonged stress-induced, ST depression-type ischemia. J Am Coll Cardiol 2001; 37:1839-45.

49. Ohtsuka T, Hamada M, Hiasa G, et al. Effect of beta-blockers on circulating levels of inflammatory and anti- inflammatory cytokines in patients with dilated cardiomyopathy. J Am Coll Cardiol 2001; 37:412-7.

50. Jenkins N, Keevil B, Hutchinson I, et al. Beta-blockers are associated with lower C-reactive protein concentrations in patients with coronary artery disease. Am J Med 2002; 112:269-74.

51. Sipahi I, Tuzcu E, Wolski K, et al. Beta-blockers and progression of coronary atherosclerosis: pooled analysis of 4 intravascular ultrasonography trials. Ann Intern Med 2007; 147:10-8.