МЕТА-АНАЛИЗ ИССЛЕДОВАНИЙ, СООБЩАВШИХ ОБ ЭФФЕКТАХ ИНГИБИТОРОВ АНГИОТЕНЗИНПРЕВРАЩАЮЩЕГО ФЕРМЕНТА И БЛОКАТОРОВ РЕЦЕПТОРОВ АНГИОТЕНЗИНА У БОЛЬНЫХ БЕЗ СЕРДЕЧНОЙ НЕДОСТАТОЧНОСТИ

Адаптированный перевод и публикация статьи осуществлены с разрешения Американской коллегии кардиологов (American College of Cardiology) под контролем экспертов РКО. Статья G. Savarese, P. Costanzo, J.G.F. Cleland, E. Vassallo, D. Ruggiero, G. Rosano, P. Perrone-Filardi «A Meta-Analysis Reporting Effects of Angiotensin-Converting Enzyme Inhibitors and Angiotensin Receptor Blockers in Patients Without Heart Failure» впервые опубликована в журнале J Am Coll Cardiol 2013;61(2):131-42; http://dx.doi.org/10.1016/j.jacc.2012.10.011

Цель. Оценить влияние ингибиторов ангиотензинпревращающего фермента (ИАПФ) и блокаторов рецепторов ангиотензина (БРА) на объединенный исход, включающий сердечно-сосудистую смерть, инфаркт миокарда (ИМ) и инсульт, а также на смертность от всех причин, возникновение сердечной недостаточности (СН) и впервые выявленного сахарного диабета (СД) в группе высокого риска у пациентов без СН.

Введение. ИАПФ уменьшают частоту сердечно-сосудистых событий в группе больных с высоким сердечно-сосудистым риском без СН, в то время как эффект БРА является менее определенным.

Материал и методы. В мета-анализ было включено 26 рандомизированных исследований, сравнивающих БРА и ИАПФ с плацебо у 108212 пациентов без СН. Проанализирован риск объединенного исхода, смертности от всех причин, возникновения СН и впервые выявленного СД.

Результаты. ИАПФ достоверно снижали риск объединенного исхода (отношение шансов [ОШ]: 0.830 [95% доверительный интервал (ДИ) 0,744-0,927], р=0,001), ИМ (ОШ:0,811 [95% ДИ 0,748-0,879], р<0,001), инсульта (ОШ: 0,796 [95% ДИ 0,682-0,928], р<0,004), смерти от всех причин (ОШ: 0,908 [95% ДИ 0,845-0,975], р=0,008), впервые возникшей СН (OШ: 0,789 [95% ДИ 0,686-0,908], р=0,001), и впервые выявленного СД (ОШ: 0,851 [95% ДИ 0,749-0,965], р<0,012). БРА достоверно снижали риск объединенного исхода (OШ: 0,920 [95% ДИ 0,869-0,975], р=0,005), инсульта (ОШ: 0.900 [95% ДИ 0,830-0,977], р=0,011), и впервые выявленного СД (ОШ: 0,855 [95% ДИ 0,798-0,915], р<0,001).

Заключение. У пациентов с высоким сердечно-сосудистым риском без СН ИАПФ и БРА снижали риск объединенного исхода, включавшего смерть от сердечно-сосудистых причин, инфаркт миокарда и инсульт. ИАПФ также снижали риск смерти от всех причин, впервые возникшей СН, и впервые выявленного СД. Таким образом, БРА дают ценную возможность снижения сердечно-сосудистой заболеваемости и смертности у пациентов, у которых невозможно применение ИАПФ

1. Yusuf S, Sleight P, Pogue J, Bosch J, Davies R, Dagenais G. Effects of an angiotensin-converting-enzyme inhibitor, ramipril, on cardiovascu- lar events in high-risk patients. The Heart Outcomes Prevention Evaluation Study Investigators. N Engl J Med 2000;342:145–3.

2. Gibbons RJ, Abrams J, Chatterjee K, et al. ACC/AHA 2002 guideline update for the management of patients with chronic stable angina—summary article: a report of the American College of Cardiology/ American Heart Association Task Force on practice guidelines. J Am Coll Cardiol 2003;41:159 – 68.

3. PROGRESS Collaborative Group. Randomized trial of a perindopril- based blood-pressure-lowering regimen among 6,105 individuals with previous stroke or transient ischemic attack. Lancet 2001;358:1033– 41.

4. Fox KM, EURopean trial On reduction of cardiac events with Perindopril in stable coronary Artery disease Investigators. Efficacy of perindopril in reduction of cardiovascular events among patients with stable coronary artery disease: randomized, double-blind, placebo-controlled, multicentre trial (the EUROPA study). Lancet 2003;362:782–8.

5. MacMahon S, Sharpe N, Gamble G, et al. Randomized, placebo-controlled trial of the angiotensin-converting enzyme inhibitor, ramipril, in patients with coronary or other occlusive arterial disease. PART-

6. Collaborative Research Group. Prevention of Atherosclerosis with Ramipril. J Am Coll Cardiol 2000;36:438–3.

7. Teo KK, Burton JR, Buller CE, et al. Long-term effects of cholesterol lowering and angiotensin-converting enzyme inhibition on coronary atherosclerosis: the Simvastatin/Enalapril Coronary Atherosclerosis Trial (SCAT). Circulation 2000;102:1748 –4.

8. Pitt B, O’Neill B, Feldman R, et al. The QUinapril Ischemic Event Trial (QUIET): evaluation of chronic ACE inhibitor therapy in patients with ischemic heart disease and preserved left ventricular function. Am J Cardiol 2001;87:1058 –3.

9. Braunwald E, Domanski MJ, Fowler SE, et al. Angiotensin-converting-enzyme inhibition in stable coronary artery disease. PEACE Trial Investigators. N Engl J Med 2004;351:2058 –8.

10. Nissen SE, Tuzcu EM, Libby P, et al. Effect of antihypertensive agents on cardiovascular events in patients with coronary disease and normal blood pressure: the CAMELOT study: a randomized controlled trial. JAMA 2004;292:2217–5.

11. Marre M, Lievre M, Chatellier G, et al. Effects of low dose ramipril on cardiovascular and renal outcomes in patients with type 2 diabetes and raised excretion of urinary albumin: randomized, double blind, placebo controlled trial (the DIABHYCAR study). BMJ 2004;328: 495–00.

12. DREAM Trial Investigators, Bosch J, Yusuf S, et al. Effect of ramipril on the incidence of diabetes. N Engl J Med 2006;355:155–2.

13. Rouleau JL, Warnica WJ, Baillot R, et al. Effects of angiotensin-converting enzyme inhibition in lowrisk patients early after coronary artery bypass surgery. Circulation 2008;117:24–1.

14. Dagenais GR, Pogue J, Fox K, Simoons ML, Yusuf S. Angiotensin-converting enzyme inhibitors in stable vascular disease without left ventricular systolic dysfunction or heart failure: a combined analysis of three trials. Lancet 2006;368:581–8.

15. Cipollone F, Fazia ML, Mezzetti A. Role of angiotensin II receptor blockers in atherosclerotic plaque stability. Expert Opin Pharmacother 2006;7:277–85.

16. Struthers AD. Aldosterone escape during ACE inhibitor therapy in chronic heart failure. Eur Heart J 1995;16:103–.

17. Casas JP, Chua W, Loukogeorgakis S, et al. Effect of inhibitors of the renin-angiotensin system and other antihypertensive drugs on renal outcomes: systematic review and meta-analysis. Lancet 2005;366:2026–3.

18. Chaturvedi N, Porta M, Klein R, et al. Effect of candesartan on prevention (DIRECT-Prevent 1) and progression (DIRECT-Protect 1) of retinopathy in type 1 diabetes: randomised, placebo-controlled trials.Lancet 2008;372:1394–02.

19. Sjolie AK, Klein R, Porta M, et al. Effect of candesartan on progression and regression of retinopathy in type 2 diabetes (DIRECT-Protect 2): a randomized placebo-controlled trial. Lancet 2008;372:1385– 93.

20. Demers C, McMurray JJ, Swedberg K, et al. Impact of candesartan on nonfatal myocardial infarction and cardiovascular death in patients with heart failure. JAMA 2005;294:1794–.

21. Parving HH, Lehnert H, Brochner-Mortensen J, et al. The effect of irbesartan on the development of diabetic nephropathy in patients with type 2 diabetes. N Engl J Med 2001;345:870–.

22. Brenner BM, Cooper ME, de Zeeuw D, et al. Effects of losartan on renal and cardiovascular outcomes in patients with type 2 diabetes and nephropathy. N Engl J Med 2001;345:861–.

23. Berl T, Hunsicker LG, Lewis JB, et al. Cardiovascular outcomes in the Irbesartan Diabetic Nephropathy Trial of patients with type 2 diabetes and overt nephropathy. Collaborative Study Group. Ann Intern Med 2003;138:542–.

24. Kondo J, Sone T, Tsuboi H, et al. Effects of low-dose angiotensin II receptor blocker candesartan on cardiovascular events in patients with coronary artery disease. Am Heart J 2003;146:E20–25.

25. Lithell H, Hansson L, Skoog I, et al. The Study on Cognition and Prognosis in the Elderly (SCOPE): principal results of a randomized double-blind intervention trial. J Hypertens 2003;21:875–6.

26. Imai E, Ito S, Haneda M, Chan JC, Makino H, ORIENT Investigators. Olmesartan reducing incidence of end stage renal disease in diabetic nephropathy trial (ORIENT): rationale and study design. Hypertens Res 2006;29:703–.

27. Yusuf S, Diener HC, Sacco RL, et al. Telmisartan to prevent recurrent stroke and cardiovascular events. N Engl J Med 2008; 359:1225–7.

28. Telmisartan Randomized AssessmeNt Study in ACE iNtolerant subjects with cardiovascular Disease (TRANSCEND) Investigators, Yusuf S, Teo K, et al. Effects of the angiotensin-receptor blocker telmisartan on cardiovascular events in high-risk patients intolerant to angiotensin-converting enzyme inhibitors: a randomized controlled trial. Lancet 2008;372:1174–3.

29. NAVIGATOR Study Group, McMurray JJ, Holman RR, et al. Effect of valsartan on the incidence of diabetes and cardiovascular events. N Engl J Med 2010;362:1477–0.

30. Haller H, Ito S, Izzo JL Jr, et al. Olmesartan for the delay or prevention of micro albuminuria in type 2 diabetes. N Engl J Med 2011;364:907–7.

31. Moher D, Liberati A, Tetzlaff J, Altman DG; PRISMA Group. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. J Clin Epidemiol 2009;62:1006 –2.

32. Savarese G, Paolillo S, Costanzo P, et al. Do changes of 6-minute walk distance predict clinical events in patients with pulmonary arterial hypertension? A meta-analysis of 22 randomized trials. J Am Coll Cardiol 2012;60:1192–01.

33. Detsky A, Naylor C, O’Rourke K, McGeer A, L’Abbe K. Incorporating variations in the quality of individual randomized trials into meta-analysis. J Clin Epidemiol 1992;45:255–5.

34. Lewis EJ, Hunsicker LG, Bain RP, Rohde RD. The effect of angiotensin-converting enzyme inhibition on diabetic nephropathy. The Collaborative Study Group. N Engl J Med 1993;329: 1456–2.

35. Maschio G, Alberti D, Janin G, et al. Effect of the angiotensin-converting enzyme inhibitor benazepril on the progression of chronic renal insufficiency. The Angiotensin-Converting Enzyme Inhibition in Progressive Renal Insufficiency Study Group. N Engl J Med 1996;334:939–5.

36. van Vark LC, Bertrand M, Akkerhuis KM, et al. Angiotensin-converting enzyme inhibitors reduce mortality in hypertension: a meta-analysis of randomized clinical trials of renin-angiotensin-aldosterone system inhibitors involving 158,998 patients. Eur Heart J 2012;33:2088–7.

37. Sharp S 1, Sterne J. Meta-analysis. Stata Technical Bulletin Reprints 1998;7:100–.

38. Costanzo P, Perrone-Filardi P, Petretta M, et al. Calcium channel blockers and cardiovascular outcomes: a meta-analysis of 175,634 patients. J Hypertens 2009;27:1136 –1.

39. Davies HT, Crombie IK, Tavakoli M. When can odds ratios mislead? BMJ 1998;316:989 –1. 39. Whitehead A. Meta-Analysis of Controlled Clinical Trials. Chichester, England: John Wiley & Sons Inc; 2002:4.

40. Raudenbush SW. Analyzing effect sizes: random-effects models. In: Cooper HM, Hedges LV, Valentine JC, editors. The Handbook of Research Synthesis and Meta-Analysis. New York, NY: Russell SAGE Foundation; 2009:306 –. 41. Sharp SJ. Meta-analysis regression. Stata Technical Bulletin 1998;42:16 –2.

41. Thompson SG, Sharp SJ. Explaining heterogeneity in meta-analysis: a comparison of methods. Stat Med 1999;18:2693–08.

42. Peters JL, Sutton AJ, Jones DR, Abrams KR, Rushton L. Comparison of two methods to detect publication bias in meta-analysis. JAMA 2006;295:676–0.

43. Baker WL, Coleman CI, Kluger J, et al. Systematic review: comparative effectiveness of angiotensinconverting enzyme inhibitors or angiotensin II-receptor blockers for ischemic heart disease. Ann Intern Med 2009;151:861–1.

44. Bangalore S, Kumar S, Wetterslev J, Messerli FH. Angiotensin receptor blockers and risk of myocardial infarction: meta-analyses and trial sequential analyses of 147 020 patients from randomised trials. BMJ 2011;342:d2234–8.

45. McAlister FA, Renin Angiotensin System Modulator Meta-Analysis Investigators. Angiotensin-converting enzyme inhibitors or angiotensin receptor blockers are beneficial in normotensive atherosclerotic patients: a collaborative meta-analysis of randomized trials. Eur Heart J 2012;33:505–8.

46. Thompson SG, Higgins JPT. How should meta-regression analyses be undertaken and interpreted. Statist Med 2002;21:1559 –3.

47. ONTARGET Investigators, Yusuf S, Teo KK, et al. Telmisartan, ramipril, or both in patients at high risk for vascular events. ONTARGET Investigators. N Engl J Med 2008;358:1547–9.