Effectiveness of Nicorandil for Reperfusion of Acute Myocardial Infarction: A Meta-Analysis_Chinese Journal of Evidence-Based Medicine

Authors：

CHEN Qingjie ¹ ,  YANG Yining ¹ , MA Yitong ¹ , LI Xiaomei ¹ , XIE Xiang ¹ , YU Zixiang ¹ , GUO Hai ²

1. Department of Cardiology, The First Affiliated Hospital of Xinjiang Medical University, Urumqi 830054, China; 2. Department of Anesthesiology, The First Affiliated Hospital of Xinjiang Medical University, Urumqi 830054, China;

Corresponding author：

YANG Yining, Email: yangyn5126@163.com

Keywords：

Nicorandil; Acute myocardial infarction; Reperfusion; Meta-analysis; Randomized controlled trial

DOI：

10.7507/1672-2531.20120208

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Objective 　To evaluate the effectiveness of nicorandil for reperfusion of acute myocardial infarction (AMI), so as to provide high quality evidence for formulating the rational AMI therapy.
Methods 　Databases including The Cochrane Library (Issue 3, 2012), PubMed, EMbase, HighWire, CBM, and CNKI were searched to collect randomized controlled trials (RCTs) on nicorandil in AMI reperfusion published before March 2012. Two reviewers independently screened literature according to the inclusion and exclusion criteria, extracted data, and evaluated the methodological quality of the included studies. Then the meta-analysis was conducted using RevMan5.1 software.
Results 　A total of 11 trials involving 1 027 patients were included. The results of meta-analyses showed that: for AMI reperfusion, nicorandil could decrease the non-reflow or slow flow rate (RR=0.34, 95%CI 0.19 to 0.61, P=0.000 3), improve the left ventricular ejection fraction (MD=5.49, 95%CI 4.51 to 6.47, P lt;0.000 01), reduce the left ventricular end-diastolic volume (MD=–14.38, 95%CI –17.31 to –11.45, P lt;0.000 01), and decrease the incidence of cardiac adverse events (RR=0.34, 95%CI 0.25 to 0.46, P lt;0.000 01), readmission rate (RR=0.33, 95%CI 0.17 to 0.63, P=0.000 8) and mortality rate (RR=0.40, 95%CI 0.16 to 0.97, P=0.04).
Conclusion 　Current evidence shows that nicorandil used as an adjuvant for AMI reperfusion can increase coronary microcirculation, improve prognosis, and decrease the incidence of cardiac adverse events, readmission and mortality rate. Due to the limited quality and quantity of the included studies, this conclusion still needs to be further proved by performing more large-scale and high quality RCTs, so we suggest clinician should adopt rational therapies based on patient’s conditions.

Citation： CHEN Qingjie,YANG Yining,MA Yitong,LI Xiaomei,XIE Xiang,YU Zixiang,GUO Hai. Effectiveness of Nicorandil for Reperfusion of Acute Myocardial Infarction: A Meta-Analysis. Chinese Journal of Evidence-Based Medicine, 2012, 12(11): 1130-1138. doi: 10.7507/1672-2531.20120208 Copy

1.	Kevelaitis E, Oubenaissa A, Peynet J, et al. Precon-ditioning by mitochondrial ATP-sensitive potassium channel openers: An effective approach for improving the preservation of heart trans-plants. Circulation, 1999, 100(19): 345-350.
2.	Mizumura T, Nithipatikom K, Gross GJ, et al. an ATP-sensitive potassium channel opener, mimics the effects of ischemic pre-conditioning to reduce infarct size, adenosine release, and neutron- phil function in dogs. Circulation, 1995, 92 (5): 1236-1245.
3.	Yao Z, Gross GJ. Activation of ATP-sensitive potassium channels lowers threshold for ischemic preconditioning in dogs. Am J Physiol, 1994, 267(5): 1888-1894.
4.	Matsuda N, Morgan KG, Sellke FW. Preconditioning improves car-dioplegia-related coronary microvascular smooth muscle hypercon-tractility: Role of KATP channels. J Thorac Cardiovasc Surg, 1999, 118(3): 438-445.
5.	Ren Z, Yang Q, Floten HS, et al. ATP-sen-sitive potassium channel opener may mimic the effects of hypoxic preconditioning on the coronary artery. Ann Thorac Surg, 2001, 71(2): 642-647.
6.	Ito H, Taniyama Y, Iwakura K, et al. Intravenous nicorandil can preserve microvascular integrity and myocardial viability in patients with reperfused anterior wall myocardial infarction. J Am Coll Cardiol, 1999, 33(3): 654-660.
7.	Kita M, Asakura M, Kim J, et al. Human atrial natriure ticpeptide and nicorandil as adjuncts to reperfusion treatment for acute myocardial infarction (J-WIND): Two randomised trials. Lancet, 2007, 370(9597): 1483-1493.
8.	Tadasu A, Katsuhiro S, Yoshihito I, et al. Continuous administration of nicorandil decreases QT dispersion during the chronic phase of acute myocardial infarction. Int Heart J, 2006, 47(3): 351-361.
9.	Fujiwara T, Matsunaga T, Kameda K, et al. Nicorandil suppresses the increases in plasma level of matrix metalloproteinase activity and attenuates left ventricular remodeling in patients with acute myocardial infarction. Heart Vessels, 2007, 22 (5): 303-309.
10.	Nameki M, Ishibashi I, Miyazaki Y, et al. Comparison between nicorandil and magnesium as an adjunct cardioprotective agent to percutaneous coronary intervention in acute anterior myocardial infarction. Circ J, 2004, 68(3): 192-197.
11.	Ono H, Osanai T, Ishizaka H, et al. Nicorandil improves cardiac function and clinical outcome in patients with acute myocardial infarction undergoing primary percutaneous coronary intervention: Role of inhibitory effect on reactive oxygen species formation. Am Heart J, 2004, 148(4): 15.
12.	Ishii H, Ichimiya S, Kanashiro M, et al. Impact of a single intravenous administration of nicorandil before reperfusion in patients with ST-segment-elevation myocardial infarction. Circulation, 2005, 112(9): 1284-1288.
13.	Ota S, Nishikawa H, Takeuchi M, et al. Impact of nicorandil to prevent reperfusion injury in patients with acute myocardial infarction: Sigmart Multicenter Angioplasty Revascularization Trial (SMART). Circ J, 2006, 70(9): 1099-1104.
14.	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(9): 1425-1429.
15.	王秀娟. 尼可地尔对急性心肌梗死患者短期预后的影响. 中国临床医学. 2009, 16(3): 344-345.
16.	Kobayashi Y, Goto Y, Daikoku S, et al. Cardioprotective effect of intravenous nicorandil in patients with successful reperfusion for acute myocardial infarction. Jpn Circ J, 1998, 62(3): 183-189.
17.	Ito H, TaniyamaY, Iwakura K, et al. Intravenous nicorandil can preserve microvascular integrity and myocardial viability in patients with reperfused anterior wall myocardial infarction. J Am Coll Cardiol, 1999, 33(3): 654-660.
18.	陈亚想, 陈山, 王金福, 等. 尼可地尔心脏缺血预处理联合溶栓治疗在急性心肌梗死中的近期疗效观察. 中国医师进修杂志·综合版. 2011, 34(13): 58-59.
19.	Dargie HJ, Ford I, Fox KM. Effect of nicorandil on coronary events in patients with stable angina: The Impact Of Nicorandil in Angina (IONA) randomised trial. Lancet, 2002, 359(9314): 1269-1275.
20.	Horinaka S, Yabe A, Yagi H, et al. Effects of nicorandil on cardiovascular events in patients with coronary artery disease in the Japanese coronary artery disease (JCAD) study. Circ J, 2010, 74(3): 503-509.
21.	Kasama S, Toyama T, Sumino H, et al. Long-term nicorandil therapy improves cardiac sympathetic nerve activity after reperfusion therapy in patients with ?rst acute myocardial infarction. J Nucl Med, 2007, 48(10): 1676-1682.
22.	Krumenacker M, Roland E. Clinical pro?le of nicorandil: an overview of its hemodynamic properties and therapeutic ef?cacy. J Cardiovasc Pharmacol, 1992, 20(3): 93-102.
23.	Ikeda N, Yasu T, Kubo N, et al. Nicorandil versus isosorbide dinitrate as adjunctive treatment to direct balloon angioplasty in acute myocardial infarction. Heart, 2004, 90(2): 181-185.
24.	Asakura M, Kitakaze M. Cardioprotection in the clinical setting-lessons from J-WIND studies. Cardiovasc Drugs Ther, 2010, 24(3): 289-295.

1. Kevelaitis E, Oubenaissa A, Peynet J, et al. Precon-ditioning by mitochondrial ATP-sensitive potassium channel openers: An effective approach for improving the preservation of heart trans-plants. Circulation, 1999, 100(19): 345-350.
2. Mizumura T, Nithipatikom K, Gross GJ, et al. an ATP-sensitive potassium channel opener, mimics the effects of ischemic pre-conditioning to reduce infarct size, adenosine release, and neutron- phil function in dogs. Circulation, 1995, 92 (5): 1236-1245.
3. Yao Z, Gross GJ. Activation of ATP-sensitive potassium channels lowers threshold for ischemic preconditioning in dogs. Am J Physiol, 1994, 267(5): 1888-1894.
4. Matsuda N, Morgan KG, Sellke FW. Preconditioning improves car-dioplegia-related coronary microvascular smooth muscle hypercon-tractility: Role of KATP channels. J Thorac Cardiovasc Surg, 1999, 118(3): 438-445.
5. Ren Z, Yang Q, Floten HS, et al. ATP-sen-sitive potassium channel opener may mimic the effects of hypoxic preconditioning on the coronary artery. Ann Thorac Surg, 2001, 71(2): 642-647.
6. Ito H, Taniyama Y, Iwakura K, et al. Intravenous nicorandil can preserve microvascular integrity and myocardial viability in patients with reperfused anterior wall myocardial infarction. J Am Coll Cardiol, 1999, 33(3): 654-660.
7. Kita M, Asakura M, Kim J, et al. Human atrial natriure ticpeptide and nicorandil as adjuncts to reperfusion treatment for acute myocardial infarction (J-WIND): Two randomised trials. Lancet, 2007, 370(9597): 1483-1493.
8. Tadasu A, Katsuhiro S, Yoshihito I, et al. Continuous administration of nicorandil decreases QT dispersion during the chronic phase of acute myocardial infarction. Int Heart J, 2006, 47(3): 351-361.
9. Fujiwara T, Matsunaga T, Kameda K, et al. Nicorandil suppresses the increases in plasma level of matrix metalloproteinase activity and attenuates left ventricular remodeling in patients with acute myocardial infarction. Heart Vessels, 2007, 22 (5): 303-309.
10. Nameki M, Ishibashi I, Miyazaki Y, et al. Comparison between nicorandil and magnesium as an adjunct cardioprotective agent to percutaneous coronary intervention in acute anterior myocardial infarction. Circ J, 2004, 68(3): 192-197.
11. Ono H, Osanai T, Ishizaka H, et al. Nicorandil improves cardiac function and clinical outcome in patients with acute myocardial infarction undergoing primary percutaneous coronary intervention: Role of inhibitory effect on reactive oxygen species formation. Am Heart J, 2004, 148(4): 15.
12. Ishii H, Ichimiya S, Kanashiro M, et al. Impact of a single intravenous administration of nicorandil before reperfusion in patients with ST-segment-elevation myocardial infarction. Circulation, 2005, 112(9): 1284-1288.
13. Ota S, Nishikawa H, Takeuchi M, et al. Impact of nicorandil to prevent reperfusion injury in patients with acute myocardial infarction: Sigmart Multicenter Angioplasty Revascularization Trial (SMART). Circ J, 2006, 70(9): 1099-1104.
14. 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(9): 1425-1429.
15. 王秀娟. 尼可地尔对急性心肌梗死患者短期预后的影响. 中国临床医学. 2009, 16(3): 344-345.
16. Kobayashi Y, Goto Y, Daikoku S, et al. Cardioprotective effect of intravenous nicorandil in patients with successful reperfusion for acute myocardial infarction. Jpn Circ J, 1998, 62(3): 183-189.
17. Ito H, TaniyamaY, Iwakura K, et al. Intravenous nicorandil can preserve microvascular integrity and myocardial viability in patients with reperfused anterior wall myocardial infarction. J Am Coll Cardiol, 1999, 33(3): 654-660.
18. 陈亚想, 陈山, 王金福, 等. 尼可地尔心脏缺血预处理联合溶栓治疗在急性心肌梗死中的近期疗效观察. 中国医师进修杂志·综合版. 2011, 34(13): 58-59.
19. Dargie HJ, Ford I, Fox KM. Effect of nicorandil on coronary events in patients with stable angina: The Impact Of Nicorandil in Angina (IONA) randomised trial. Lancet, 2002, 359(9314): 1269-1275.
20. Horinaka S, Yabe A, Yagi H, et al. Effects of nicorandil on cardiovascular events in patients with coronary artery disease in the Japanese coronary artery disease (JCAD) study. Circ J, 2010, 74(3): 503-509.
21. Kasama S, Toyama T, Sumino H, et al. Long-term nicorandil therapy improves cardiac sympathetic nerve activity after reperfusion therapy in patients with ?rst acute myocardial infarction. J Nucl Med, 2007, 48(10): 1676-1682.
22. Krumenacker M, Roland E. Clinical pro?le of nicorandil: an overview of its hemodynamic properties and therapeutic ef?cacy. J Cardiovasc Pharmacol, 1992, 20(3): 93-102.
23. Ikeda N, Yasu T, Kubo N, et al. Nicorandil versus isosorbide dinitrate as adjunctive treatment to direct balloon angioplasty in acute myocardial infarction. Heart, 2004, 90(2): 181-185.
24. Asakura M, Kitakaze M. Cardioprotection in the clinical setting-lessons from J-WIND studies. Cardiovasc Drugs Ther, 2010, 24(3): 289-295.

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