ВЛИЯНИЕ НИКОРАНДИЛА НА ЧАСТОТУ СЕРДЕЧНО-СОСУДИСТЫХ СОБЫТИЙ У ПАЦИЕНТОВ С КОРОНАРНОЙ БОЛЕЗНЬЮ СЕРДЦА – УЧАСТНИКОВ ИССЛЕДОВАНИЯ JCAD (JAPANESE CORONARY ARTERY DISEASE STUDY)

В условиях ишемии миокарда никорандил обладает кардиопротективным действием за счет воспроизведения эффектов ишемического прекондиционирования. Таким образом, можно предположить, что данный препарат способен улучшать прогноз у пациентов с коронарной болезнью сердца (КБС). В рамках многоцентрового проспективного, обсервационного исследования JCAD (Japanese Coronary Artery Disease Study) был изучен эффект никорандила на частоту различных конечных точек. В целом, из 13812 пациентов, скринированных в рамках исследования JCAD, отвечали критериям включения 2588 принимавших никорандил пациентов и столько же подобранных по индексу соответствия лиц из группы контроля. Среднее время наблюдения составило 2,7 года. Частота основной конечной точки – смерти от любых причин – была достоверно ниже (-35%; отношение рисков (ОР) – 0,65, р=0,0008) в группе никорандила по сравнению с группой контроля. Также в группе никорандила отмечалось достоверное снижение частоты дополнительных конечных точек – сердечной смерти (-56%), фатального инфаркта миокарда (-56%), цереброваскулярной и сосудистой смерти (-71%), а также застойной сердечной недостаточности (-33%) без увеличения частоты смерти иной, не сердечно-сосудистой этиологии. Степень снижения частоты смерти любой этиологии на фоне терапии никорандилом не зависела от одновременного приема препаратов сульфанилмочевины. У пациентов с КБС прием никорандила сопровождался существенным снижением частоты сердечно-сосудистой смерти. Полученные результаты могут иметь важное значение для выбора тактики лечения в данной группе больных.

1. Taira N. Nicorandil as a hybrid between nitrates and potassium channel activators. Am J Cardiol 1989; 63: 18J – 24J.

2. Holzmann S. Cyclic GMP as possible mediator of coronary arterial relaxation by Nicorandil (SG-75) // J Cardiovasc Pharmacol 1983; 5: 364 – 370.

3. Grover GJ. Pharmacology of ATP-sensitive potassium channel (KATP) openers in models of myocardial ischemia and reperfusion // Can J Physiol Pharmacol 1997; 75: 309 – 315.

4. Ohno Y, Minatoguchi S, Uno Y et al. Nicorandil reduces myocardial infarct size by opening the KATP channel in rabbits // Int J Cardiol 1997; 62: 181 – 190.

5. Schultz JE, Yao Z, Cavero I et al. Glibenclamide-induced blockade of ischemic preconditioning is time dependent in intact rat heart // Am J Physiol 1997; 272: H2607 – H2615.

6. Iwakura K, Ito H, Okamura A, Koyama Y et al. Nicorandil treatment in patients with acute myocardial infarction: A meta-analysis // Circ J 2009; 73: 925 – 931.

7. Lee HC, An SG, Choi JH et al. Effect of intra-coronary nicorandil administration prior to reperfusion in acute ST segment elevation myocardial infarction // Circ J 2008; 72: 1425 – 1429.

8. IONA Study Group. Effect of nicorandil on coronary events in patients with stable angina: The Impact Of Nicorandil in Angina (IONA) randomized trial // Lancet 2002; 359: 1269 – 1275.

9. The Japanese Coronary Artery Disease (JCAD) Study Investigators. Current status of the background of patients with coronary artery disease in Japan: The Japanese Coronary Artery Disease Study (The JCAD Study) // Circ J 2006; 70: 1256 – 1262.

10. Kambara H, Yamazaki T, Hayashi D et al. Gender differences in patients with coronary artery disease in Japan: The Japanese Coronary Artery Disease Study (the JCAD study) // Circ J 2009; 73: 912 – 917.

11. Okura T, Higaki J, Kurata M et al. Elevated serum uric acid is an independent predictor for cardiovascular events in patients with severe coronary artery stenosis: Subanalysis of the Japanese Coronary Artery Disease (JCAD) Study // Circ J 2009; 73: 885 – 891.

12. D’Agostino RB Jr. Propensity score methods for bias reduction in the comparison of a treatment to a non-randomized control group // Stat Med 1998; 17: 2265 – 2281.

13. Chambless L, Keil U, Dobson A et al. Population versus clinical view of case fatality from acute coronary heart disease: Results from the WHO MONICA Project 1985 – 1990: Multinational MONItoring of Trends and Determinants in CArdiovascular Disease // Circulation 1997; 96: 3849 – 3859.

14. Sans S, Kesteloot H, Kromhout D. The burden of cardiovascular diseases mortality in Europe: Task Force of the European Society of Cardiology on Cardiovascular Mortality and Morbidity Statistics in Europe // Eur Heart J 1997; 18: 1231 – 1248.

15. IONA Study Group. Impact of nicorandil in angina: Subgroup analyses // Heart 2004; 90: 1427 – 1430.

16. Miura T, Liu Y, Kita H et al. Roles of mitochondria ATP-sensitive K channels and PKC in anti-infarct tolerance afforded by adenosine A1 receptor activation // J Am Coll Cardiol 2000; 35: 238 – 245.

17. Fukuda H, Luo CS, Guo LL et al. The effect of KATP channel activation on myocardial cationic and energetic status during ischemia and reperfusion: Role in cardioprotection // J Mol Cell Cardiol 2001; 33: 545 – 560.

18. Maczewski M, Bercewicz A. The role of adenosine and ATPsensitive potassium channels in the protection afforded by ischemic preconditioning against the post-ischemic endothelial dysfunction in guinea-pig hearts // J Mol Cell Cardiol 1998; 30: 1735 – 1747.

19. Ren Z, Yang Q, Floten HS, Furnary AP, Yim AP, He GW. ATPsensitive potassium channel openers may mimic the effects of hypoxic preconditioning on the coronary artery // Ann Thorac Surg 2001; 71: 642 – 647.

20. Patel DJ, Purcell HJ, Fox KM. Cardioprotection by opening of the K (ATP) channel in unstable angina: Is this a clinical manifestation of myocardial preconditioning? Results of a randomized study with nicorandil. CESAR 2 investigation. Clinical European studies in angina and revascularization // Eur Heart J 1999; 20: 51 – 57.

21. Simpson D, Wellington K. Nicorandil: A review of its use in the management of stable angina pectoris, including high risk patients// Drugs 2004; 64: 1941 – 1955.

22. Kato T, Kamiyama T, Maruyama Y et al. Nicorandil, a potent cardioprotective agent, reduces QT dispersion during coronary angioplasty // Am Heart J 2001; 141: 940 – 943.

23. Ishii H, Toriyama T, Aoyama T et al. Efficacy of oral nicorandil in patients with end-stage renal disease: A retrospective chart review after coronary angioplasty in Japanese patients receiving hemodialysis // Clin Ther 2007; 29: 110 – 122.

24. Sekiya M, Sato M, Funada J et al. Effect of the long-term administration of nicorandil on vascular endothelial function and the progression of arteriosclerosis// J Cardiovasc Pharmacol 2005; 46: 63 – 67.

25. Kasama S, Toyama T, Hatori T et al. Comparative effects of nicorandil with isosorbide mononitrate on cardiac sympathetic nerve activity and left ventricular function in patients with ischemic cardiomyopathy// Am Heart J 2005; 150: 477.e1 – 477.e8.

26. Sanada S, Node K, Asanuma H et al. Opening of the adenosine triphosphate-sensitive potassium channel attenuates cardiac remodeling induced by long-term inhibition of nitric oxide synthesis: Role of 70-kDa S6 kinase and extracellular signal-regulated kinase// J Am Coll Cardiol 2002; 40: 991 – 997.

27. Horinaka S, Kobayashi N, Yagi H et al. Nicorandil but not ISDN upregulates endothelial nitric oxide synthase expression, preventing left ventricular remodeling and degradation of cardiac function in Dahl salt-sensitive hypertension rats with congestive heart failure// J Cardiovasc Pharmacol 2006; 47: 629 – 635.

28. Kitakaze M, Asakura M, Kim J et al. Human atrial natriuretic peptide and nicorandil as adjuncts to reperfusion treatment for acute myocardial infarction (J-WIND): Two randomized trials // Lancet 2007; 370: 1483 – 1493.

29. Gribble FM, Ashcroft FM. Differential sensitivity of beta-cell and extrapancreatic KATP channel to gliclazide// Diabetologia 1999; 42: 845 – 848.

30. Mocanu MM, Maddock HL, Baxter GF et al. Glimepiride, a novel sulfonylurea, does not abolish myocardial protection afforded by either ischemic preconditioning or diazoxide//Circulation 2001; 103: 311 – 316.

31. Lee TM, Chou TF. Impairment of myocardial protection in type 2 diabetic patients // J Clin Endocrinol Metab 2003; 88: 531 – 537. Circulation Vol.74, March 2010