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Drugs
Published in: Drugs 9/2011

01-06-2011 | Current Opinion

Use of Nicorandil in Cardiovascular Disease and Its Optimization

Author: Dr Shigeo Horinaka

Published in: Drugs | Issue 9/2011

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Abstract

Nicorandil, a unique dual pharmacological mechanism anti-anginal agent with adenosine triphosphate sensitive potassium (KATP) channel agonist and nitrate-like properties, provides cardiologists with a means of managing angina pectoris patients effectively and provides long-term cardioprotection. The aim of this review is to provide an update on the efficacy of treatment with nicorandil, which counteracts cardiac damage in patients with acute or chronic ischaemic heart disease, congestive heart failure and arrhythmia, with particular emphasis on that induced by ischaemic preconditioning (in which strong protection against ischaemia-reperfusion injury is afforded by a brief preliminary ischaemic period). First, the rationale for nicorandil treatment and its pharmacological effects on the vasculature and cardiomyocytes are reviewed. The mechanisms underlying ischaemic preconditioning, with a focus on those that involve the KATP channel pathway, such as mitochondrial permeability transition pores, sub-lethal reactive oxygen species generation and nitric oxide production are then discussed. Next, clinical practice related to ischaemic preconditioning and pharmacological preconditioning with nicorandil as well as other favourable mechanisms of improvement of prognosis, in which it plays a role in improving endothelial function, modulating autonomic nervous system activity and stabilizing plaque are summarized. Finally, the tolerability of nicorandil is discussed.
Literature
1.
Boden WE, O’Rourke RA, Teo KK, et al. Optimal medical therapy with or without PCI for stable coronary disease. N Engl J Med 2007 Apr 12; 356(15): 1503–16PubMedCrossRef
2.
Frye RL, August P, Brooks MM et al. A randomized trial of therapies for type 2 diabetes and coronary artery disease. N Engl J Med 2009 Jun 11; 360(24): 2503–15PubMedCrossRef
3.
Hochman JS, Lamas GA, Buller CE, et al. Coronary intervention for persistent occlusion after myocardial infarction. N Engl J Med 2006 Dec 7; 355(23): 2395–407PubMedCrossRef
4.
Henderson RA, Pocock SJ, Clayton TC, et al. Seven-year outcome in the RITA-2 trial: coronary angioplasty versus medical therapy. J Am Coll Cardiol 2003 Oct 1; 42(7): 1161–70PubMedCrossRef
5.
Fraker Jr TD, Fihn SD, 2002 Chronic Stable Angina Writing Committee, American College of Cardiology, American Heart Association. 2007 chronic angina focused update of the ACC/AHA 2002 guidelines for the management of patients with chronic stable angina: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines Writing Group to develop the focused update of the 2002 guidelines for the management of patients with chronic stable angina. J Am Coll Cardiol 2007 Dec 4; 50(23): 2264–74PubMedCrossRef
6.
Fox K, Garcia MA, Ardissino D, et al. Guidelines on the management of stable angina pectoris: executive summary: the Task Force on the Management of Stable Angina Pectoris of the European Society of Cardiology. Eur Heart J 2006 Jun; 27(11): 1341–81PubMedCrossRef
7.
Taira N. Nicorandil as a hybrid between nitrates and potassium channel activators. Am J Cardiol 1989 Jun 20; 63(21): 18J–24JPubMedCrossRef
8.
Kukovetz WR, Holzmann S, Braida C, et al. Dual mechanism of the relaxing effect of nicorandil by stimulation of cyclic GMP formation and by hyperpolarization. J Cardiovasc Pharmacol 1991 Apr; 17(4): 627–33PubMedCrossRef
9.
Holzmann S, Kukovetz WR, Braida C, et al. Pharmacological interaction experiments differentiate between glibenclamide-sensitive K+ channels and cyclic GMP as components of vasodilation by nicorandil. Eur J Pharmacol 1992 Apr 29; 215(1): 1–7PubMedCrossRef
10.
Kukovetz WR, Holzmann S, Pöch G. Molecular mechanism of action of nicorandil. J Cardiovasc Pharmacol 1992; 20 Suppl. 3: S1–7PubMedCrossRef
11.
Holzmann S. Cyclic GMP as possible mediator of coronary arterial relaxation by nicorandil (SG-75). J Cardiovasc Pharmacol 1983 May–Jun; 5(3): 364–70PubMedCrossRef
12.
Frampton J, Buckley MM, Fitton A. Nicorandil: a review of its pharmacology and therapeutic efficacy in angina pectoris. Drugs 1992 Oct; 44(4): 625–55PubMedCrossRef
13.
Meany TB, Richardson P, Camm AJ, et al. Exercise capacity after single and twice daily doses of nicorandil in chronic stable angina pectoris. Am J Cardiol 1989 Jun; 63: 66J–70JPubMedCrossRef
14.
Weston AH, Longmore J, Newgreen DT, et al. The potassium channel openers: a new class of vasorelaxants. Blood Vessels 1990; 27(2-5): 306–13PubMed
15.
Gelband CH, Silberberg SD, Groschner K, et al. ATP inhibits smooth muscle Ca2(+)-activated K+ channels. Proc Biol Sci 1990 Oct 22; 242(1303): 23–8PubMedCrossRef
16.
Escande D, Cavero I. K+ channel openers and ‘natural’ cardioprotection. Trends Pharmacol Sci 1992 Jul; 13(7): 269–72PubMedCrossRef
17.
Greenberg SS, Cantor E, Ho E, et al. Comparison of nicorandil-induced relaxation, elevations of cyclic guanosine monophosphate and stimulation of guanylate cyclase with organic nitrate esters. J Pharmacol Exp Ther 1991 Sep; 258(3): 1061–71PubMed
18.
Rapoport RM, Murad F. Endothelium-dependent and nitrovasodilator-induced relaxation of vascular smooth muscle: role of cyclic GMP. J Cyclic Nucleotide Protein Phosphor Res 1983; 9(4-5): 281–96PubMed
19.
Taniguchi J, Furukawa KI, Shigekawa M. Maxi K+ channels are stimulated by cyclic guanosine monophosphate-dependent protein kinase in canine coronary artery smooth muscle cells. Pflugers Arch 1993 May; 423(3-4): 167–72PubMedCrossRef
20.
Matsui T, Amano M, Yamamoto T, et al. Rho-associated kinase, a novel serine/threonine kinase, as a putative target for small GTP binding protein Rho. EMBO J 1996 May 1; 15(9): 2208–16PubMed
21.
Carafoli E. Calcium pump of the plasma membrane. Physiol Rev 1991 Jan; 71(1): 129–53PubMed
22.
Vrolix M, Raeymaekers L, Wuytack F, et al. Cyclic GMP-dependent protein kinase stimulates the plasmalemmal Ca2+ pump of smooth muscle via phosphorylation of phosphatidylinositol. Biochem J 1988 Nov 1; 255(3): 855–63PubMed
23.
Akai K, Wang Y, Sato K, et al. Vasodilatory effect of nicorandil on coronary arterial microvessels: its dependency on vessel size and the involvement of the ATP-sensitive potassium channels. J Cardiovasc Pharmacol 1995 Oct; 26(4): 541–7PubMedCrossRef
24.
Hongo M, Takenaka H, Uchikawa S, et al. Coronary microvascular response to intracoronary administration of nicorandil. Am J Cardiol 1995 Feb 1; 75(4): 246–50PubMedCrossRef
25.
Nakae I, Quan L, Hashimoto K, et al. Mechanism of the vasodilatory action of nicorandil on coronary circulation in dogs. Cardiovasc Drugs Ther 1994 Feb; 8(1): 137–45PubMedCrossRef
26.
Kojima M, Ban T. Nicorandil shortens action potential duration and antagonises the reduction of Vmax by lidocaine but not by disopyramide in guinea-pig papillary muscles. Naunyn Schmiedebergs Arch Pharmacol 1988 Feb; 337(2): 203–12PubMedCrossRef
27.
Yanagisawa T, Taira N. Effect of 2-nicotinamidethyl nitrate (SG-75) on membrane potentials of canine Purkinje fibers. Jpn J Pharmacol 1981 Jun; 31(3): 409–17PubMedCrossRef
28.
Hirose M, Tsujino N, Nakada T, et al. Mechanisms of preventive effect of nicorandil on ischaemia-induced ventricular tachyarrhythmia in isolated arterially perfused canine left ventricular wedges. Basic Clin Pharmacol Toxicol 2008 Jun; 102(6): 504–14PubMedCrossRef
29.
Antzelevitch C, Shimizu W, Yan GX, et al. Cellular basis for QT dispersion. J Electrocardiol 1998; 30 Suppl.: 168–75PubMedCrossRef
30.
Kato T, Kamiyama T, Maruyama Y, et al. Nicorandil, a potent cardioprotective agent, reduces QT dispersion during coronary angioplasty. Am Heart J 2001 Jun; 141(6): 940–3PubMedCrossRef
31.
Ashikaga T, Nishizaki M, Arita M, et al. Opening of K(ATP) channel attenuates the increase in QT dispersion produced by the first balloon inflation during coronary angioplasty. Circ J 2002 May; 66(5): 469–72PubMedCrossRef
32.
Akagi T, Sarazawa K, Inai Y, et al. Continuous administration of nicorandil decreases QT dispersion during the chronic phase of acute myocardial infarction. Int Heart J 2006 May; 47(3): 351–61PubMedCrossRef
33.
Horinaka S, Kobayashi N, Yabe A, et al. Nicorandil protects against lethal ischemic ventricular arrhythmias and up-regulates endothelial nitric oxide synthase expression and sulfonylurea receptor 2 mRNA in conscious rats with acute myocardial infarction. Cardiovasc Drugs Ther 2004 Jan; 18(1): 13–22PubMedCrossRef
34.
Hara H, Horinaka S, Yabe A, et al. Suppressive effect of nicorandil in ventricular arrhythmias after reperfusion therapy in patients with acute myocardial infarction. J Cardiol 2007 Mar; 49(3): 135–41PubMed
35.
Ueda H, Nakayama Y, Tsumura K, et al. Intravenous nicorandil can reduce the occurrence of ventricular fibrillation and QT dispersion in patients with successful coronary angioplasty in acute myocardial infarction. Can J Cardiol 2004 May 1; 20(6): 625–9PubMed
36.
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 Jan; 20(1): 51–7PubMedCrossRef
37.
Hanai Y, Mita M, Hishinuma S, et al. A systematic review on the short-term efficacy and safety of nicorandil for stable angina pectoris in comparison with those of β-blockers, nitrates and calcium antagonists [in Japanese]. Yakugaku Zasshi 2010 Nov; 130(11): 1549–63PubMedCrossRef
38.
Hughes LO, Rose EL, Lahiri A, et al. Comparison of nicorandil and atenolol in stable angina pectoris. Am J Cardiol 1990 Sep 15; 66(7): 679–82PubMedCrossRef
39.
Meeter K, Kelder JC, Tijssen JG, et al. Efficacy of nicorandil versus propranolol in mild stable angina pectoris of effort: a long-term, double-blind, randomized study. J Cardiovasc Pharmacol 1992; 20 Suppl. 3: S59–66PubMed
40.
Di Somma S, Liguori V, Petitto M, et al. A double-blind comparison of nicorandil and metoprolol in stable effort angina pectoris. Cardiovasc Drugs Ther 1993 Feb; 7(1): 119–23PubMedCrossRef
41.
Lai C, Onnis E, Solinas R, et al. A new anti-ischemic drug for the treatment of stable effort angina pectoris: nicorandil: comparison with placebo and isosorbide-5-mononitrate [in Italian]. Cardiologia 1991 Sep; 36(9): 703–11PubMed
42.
Zhu WL, Shan YD, Guo JX, et al. Double-blind, multicenter, active-controlled, randomized clinical trial to assess the safety and efficacy of orally administered nicorandil in patients with stable angina pectoris in China. Circ J 2007 Jun; 71(6): 826–33PubMedCrossRef
43.
Döring G. Antianginal and anti-ischemic efficacy of nicorandil in comparison with isosorbide-5-mononitrate and isosorbide dinitrate: results from two multicenter, double-blind, randomized studies with stable coronary heart disease patients. J Cardiovasc Pharmacol 1992; 20 Suppl. 3: S74–81PubMedCrossRef
44.
Sasaki J, Saeki Y, Kawasaki K, et al. A multicenter comparison of nicorandil and diltiazem on serum lipid, apolipoprotein, and lipoprotein levels in patients with ischemic heart disease. Cardiovasc Drugs Ther 1992 Oct; 6(5): 471–4PubMedCrossRef
45.
Guermonprez JL, Blin P, Peterlongo F. A double-blind comparison of the long-term efficacy of a potassium channel opener and a calcium antagonist in stable angina pectoris. Eur Heart J 1993 Jul; 14 Suppl. B: 30–4PubMedCrossRef
46.
Ulvenstam G, Diderholm E, Frithz G, et al. Antianginal and anti-ischemic efficacy of nicorandil compared with nifedipine in patients with angina pectoris and coronary heart disease: a double-blind, randomized, multicenter study. J Cardiovasc Pharmacol 1992; 20 Suppl. 3: S67–73PubMedCrossRef
47.
The SWAN Study Group. Comparison of the antiischaemic and antianginal effects of nicorandil and amlodipine in patients with symptomatic stable angina pectoris: the SWAN study. J Clin Basic Cardiol 1999; 2: 213–7
48.
Kishida H, Murao S. Effect of a new coronary vasodilator, nicorandil, on variant angina pectoris. Clin Pharmacol Ther 1987 Aug; 42(2): 166–74PubMedCrossRef
49.
Lablanche JM, Bauters C, Leroy F, et al. Prevention of coronary spasm by nicorandil: comparison with nifedipine. J Cardiovasc Pharmacol 1992; 20 Suppl. 3: S82–5PubMedCrossRef
50.
Lablanche JM, Bauters C, McFadden EP, et al. Potassium channel activators in vasospastic angina. Eur Heart J 1993 Jul; 14 Suppl. B: 22–4PubMedCrossRef
51.
Kato K. Haemodynamic and clinical effects of an intravenous potassium channel opener: a review. Eur Heart J 1993 Jul; 14 Suppl. B: 40–7PubMedCrossRef
52.
Tanaka K, Kato K, Takano T, et al. Acute effects of intravenous nicorandil on hemodynamics in patients hospitalized with acute decompensated heart failure. J Cardiol 2010 Nov; 56(3): 291–9PubMedCrossRef
53.
Minami Y, Nagashima M, Kajimoto K, et al. Acute efficacy and safety of intravenous administration of nicorandil in patients with acute heart failure syndromes: usefulness of noninvasive echocardiographic hemodynamic evaluation. J Cardiovasc Pharmacol 2009 Oct; 54(4): 335–40PubMedCrossRef
54.
Tsutamoto T, Kinoshita M, Nakae I, et al. Absence of hemodynamic tolerance to nicorandil in patients with severe congestive heart failure. Am Heart J 1994 Apr; 127 (4 Pt 1): 866–73PubMedCrossRef
55.
Tsutamoto T, Kinoshita M, Hisanaga T, et al. Comparison of hemodynamic effects and plasma cyclic guanosine monophosphate of nicorandil and nitroglycerin in patients with congestive heart failure. Am J Cardiol 1995 Jun 1; 75(16): 1162–5PubMedCrossRef
56.
Larsen AI, Gøransson L, Aarsland T, et al. Comparison of the degree of hemodynamic tolerance during intravenous infusion of nitroglycerin versus nicorandil in patients with congestive heart failure. Am Heart J 1997 Sep; 134(3): 435–41PubMedCrossRef
57.
Murry CE, Jennings RB, Reimer KA. Preconditioning with ischemia: a delay of lethal cell injury in ischemic myocardium. Circulation 1986 Nov; 74(5): 1124–36PubMedCrossRef
58.
59.
Piper HM, Garcña-Dorado D, Ovize M. A fresh look at reperfusion injury. Cardiovasc Res 1998; 38(2): 291–300PubMedCrossRef
60.
Di Lisa F, Menabò R, Canton M, et al. Opening of the mitochondrial permeability transition pore causes depletion of mitochondrial and cytosolic NAD+ and is a causative event in the death of myocytes in postischemic reperfusion of the heart. J Biol Chem 2001 Jan 26; 276(4): 2571–5PubMedCrossRef
61.
Hausenloy DJ. Signalling pathways in ischaemic postconditioning. Thromb Haemost 2009 Apr; 101(4): 626–34PubMed
62.
Solaini G, Harris DA. Biochemical dysfunction in heart mitochondria exposed to ischaemia and reperfusion. Biochem J 2005 Sep 1; 390 (Pt 2): 377–94PubMedCrossRef
63.
Kevin LG, Camara AK, Riess ML, et al. Ischemic preconditioning alters real-time measure of O2 radicals in intact hearts with ischemia and reperfusion. Am J Physiol Heart Circ Physiol 2003 Feb; 284(2): H566–74PubMed
64.
Halestrap AP. Calcium, mitochondria and reperfusion injury: a pore way to die. Biochem Soc Trans 2006 Apr; 34 (Pt 2): 232–7PubMedCrossRef
65.
Halestrap AP. What is the mitochondrial permeability transition pore? J Mol Cell Cardiol 2009 Jun; 46(6): 821–31PubMedCrossRef
66.
Costa AD, Jakob R, Costa CL, et al. The mechanism by which the mitochondrial ATP-sensitive K+ channel opening and H2O2 inhibit the mitochondrial permeability transition. J Biol Chem 2006 Jul 28; 281(30): 20801–8PubMedCrossRef
67.
Kuno A, Critz SD, Cohen MV, et al. Nicorandil opens mitochondrial K(ATP) channels not only directly but also through a NO-PKG-dependent pathway. Basic Res Cardiol 2007 Jan; 102(1): 73–9PubMedCrossRef
68.
Kloner RA, Shook T, Antman EM, et al. Prospective temporal analysis of the onset of preinfarction angina versus outcome: an ancillary study in TIMI-9B. Circulation 1998 Mar 24; 97(11): 1042–5PubMedCrossRef
69.
Ishihara M, Sato H, Tateishi H, et al. Implications of prodromal angina pectoris in anterior wall acute myocardial infarction: acute angiographic findings and long-term prognosis. J Am Coll Cardiol 1997 Oct; 30(4): 970–5PubMedCrossRef
70.
Deutsch E, Berger M, Kussmaul WG, et al. Adaptation to ischemia during percutaneous transluminal coronary angioplasty: clinical, hemodynamic, and metabolic features. Circulation 1990 Dec; 82(6): 2044–51PubMedCrossRef
71.
Abdallah Y, Wolf C, Meuter K, et al. Preconditioning with diazoxide prevents reoxygenation-induced rigor-type hypercontracture. J Mol Cell Cardiol 2010 Jan; 48(1): 270–6PubMedCrossRef
72.
Tritto I, D’Andrea D, Eramo N, et al. Oxygen radicals can induce preconditioning in rabbit hearts. Circ Res 1997 May; 80(5): 743–8PubMedCrossRef
73.
Baines CP, Goto M, Downey JM. Oxygen radicals released during ischemic preconditioning contribute to cardioprotection in the rabbit myocardium. J Mol Cell Cardiol 1997 Jan; 29(1): 207–16PubMedCrossRef
74.
Ozcan C, Terzic A, Bienengraeber M. Effective pharmacotherapy against oxidative injury: alternative utility of an ATP-sensitive potassium channel opener. J Cardiovasc Pharmacol 2007 Oct; 50(4): 411–8PubMedCrossRef
75.
Sato T, Sasaki N, O’Rourke B, et al. Nicorandil, a potent cardioprotective agent, acts by opening mitochondrial ATP-dependent potassium channels. J Am Coll Cardiol 2000 Feb; 35(2): 514–8PubMedCrossRef
76.
Matsubara T, Minatoguchi S, Matsuo H, et al. Three minute, but not one minute, ischemia and nicorandil have a preconditioning effect in patients with coronary artery disease. J Am Coll Cardiol 2000 Feb; 35(2): 345–51PubMedCrossRef
77.
Matsuo H, Watanabe S, Segawa T, et al. Evidence of pharmacologic preconditioning during PTCA by intravenous pretreatment with ATP-sensitive K+ channel opener nicorandil. Eur Heart J 2003 Jul; 24(14): 1296–303PubMedCrossRef
78.
IONA Study Group. Effect of nicorandil on coronary events in patients with stable angina: the Impact Of Nicorandil in Angina (IONA) randomised trial. Lancet 2002 Apr 13; 359(9314): 1269–75CrossRef
79.
Louis AA, Manousos IR, Coletta AP, et al. Clinical trials update: The Heart Protection Study, IONA, CARISA, ENRICHD, ACUTE, ALIVE, MADIT II and REMATCH. Impact Of Nicorandil on Angina. Combination Assessment of Ranolazine In Stable Angina. ENhancing Recovery In Coronary Heart Disease patients. Assessment of Cardioversion Using Transoesophageal Echocardiography. AzimiLide post-Infarct surVival Evaluation. Randomised Evaluation of Mechanical Assistance for Treatment of Chronic Heart failure. Eur J Heart Fail 2002 Jan; 4(1): 111–6
80.
Japanese Coronary Artery Disease (JCAD) Study Investigators. Current status of the background of patients with coronary artery disease in Japan. Circ J 2006 Oct; 70(10): 1256–62CrossRef
81.
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): 503–9PubMedCrossRef
82.
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 randomised trials. Lancet 2007 Oct 27; 370(9597): 1483–93PubMedCrossRef
83.
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 Mar; 33(3): 654–60PubMedCrossRef
84.
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 Aug 30; 112(9): 1284–8PubMedCrossRef
85.
Kawai Y, Hisamatsu K, Matsubara H, et al. Intravenous administration of nicorandil immediately before percutaneous coronary intervention can prevent slow coronary flow phenomenon. Eur Heart J 2009 Apr; 30(7): 765–72PubMedCrossRef
86.
Iwakura K, Ito H, Okamura A, et al. Nicorandil treatment in patients with acute myocardial infarction: a metaanalysis. Circ J 2009 May; 73(5): 925–31PubMedCrossRef
87.
Wu KC, Zerhouni EA, Judd RM et al. Prognostic significance of microvascular obstruction by magnetic resonance imaging in patients with acute myocardial infarction. Circulation 1998 Mar 3; 97(8): 765–72PubMedCrossRef
88.
Hombach V, Grebe O, Merkle N, et al. Sequelae of acute myocardial infarction regarding cardiac structure and function and their prognostic significance as assessed by magnetic resonance imaging. Eur Heart J 2005 Mar; 26(6): 549–57PubMedCrossRef
89.
Kasama S, Toyama T, Sumino H, et al. Long-term nicorandil therapy improves cardiac sympathetic nerve activity after reperfusion therapy in patients with first acute myocardial infarction. J Nucl Med 2007 Oct; 48(10): 1676–82PubMedCrossRef
90.
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 Sep; 150(3): 477.e1-477.e8PubMedCrossRef
91.
Kang CS, Chen CC, Lin CC, et al. Effect of ATP-sensitive potassium channel agonists on sympathetic hyperinnervation in postinfarcted rat hearts. Am J Physiol Heart Circ Physiol 2009 Jun; 296(6): H1949–59PubMedCrossRef
92.
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 Sep; 40(5): 991–7PubMedCrossRef
93.
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 hypertensive rats with congestive heart failure. J Cardiovasc Pharmacol 2006 May; 47(5): 629–35PubMedCrossRef
94.
Sekiya M, Sato M, Funada J, et al. Effects of the long-term administration of nicorandil on vascular endothelial function and the progression of arteriosclerosis. J Cardiovasc Pharmacol 2005 Jul; 46(1): 63–7PubMedCrossRef
95.
Ishibashi Y, Takahashi N, Tokumaru A, et al. Effects of long-term nicorandil administration on endothelial function, inflammation, and oxidative stress in patients without coronary artery disease. J Cardiovasc Pharmacol 2008 Mar; 51(3): 311–6PubMedCrossRef
96.
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 Jan; 29(1): 110–22PubMedCrossRef
97.
Nishimura M, Tokoro T, Nishida M, et al. Clinical potential of nicorandil to inhibit major cardiac events in hemodialysis patients with suspected myocardial ischemia. Nephron Clin Pract 2009; 111(3): c212–21PubMedCrossRef
98.
Nishimura M, Tokoro T, Nishida M, et al. Oral nicorandil to reduce cardiac death after coronary revascularization in hemodialysis patients: a randomized trial. Am J Kidney Dis 2009 Aug; 54(2): 307–17PubMedCrossRef
99.
Dikow R, Kihm LP, Zeier M, et al. Increased infarct size in uremic rats: reduced ischemia tolerance? J Am Soc Nephrol 2004 Jun; 15(6): 1530–6PubMedCrossRef
100.
Rostand SG, Brunzell JD, Cannon 3rd RO, et al. Cardiovascular complications in renal failure. J Am Soc Nephrol 1991 Dec; 2(6): 1053–62PubMed
101.
Parfrey PS, Foley RN, Harnett JD, et al. Outcome and risk factors of ischemic heart disease in chronic uremia. Kidney Int 1996 May; 49(5): 1428–34PubMedCrossRef
102.
Herzog CA, Ma JZ, Collins AJ. Poor long-term survival after acute myocardial infarction among patients on longterm dialysis. N Engl J Med 1998 Sep 17; 339(12): 841–3CrossRef
103.
Hodgson DM, Zingman LV, Kane GC, et al. Cellular remodeling in heart failure disrupts K(ATP) channeldependent stress tolerance. EMBO J 2003 Apr 15; 22(8): 1732–42PubMedCrossRef
104.
Izumiya Y, Kojima S, Kojima S, et al. Long-term use of oral nicorandil stabilizes coronary plaque in patients with stable angina pectoris. Atherosclerosis 2011 Feb; 214(2): 415–21PubMedCrossRef
105.
Eguchi Y, Takahari Y, Higashijima N, et al. Nicorandil attenuates FeCl(3)-induced thrombus formation through the inhibition of reactive oxygen species production. Circ J 2009 Mar; 73(3): 554–61PubMedCrossRef
106.
Simpson D, Wellington K. Nicorandil: a review of its use in the management of stable angina pectoris, including highrisk patients. Drugs 2004; 64(17): 1941–55PubMedCrossRef
107.
Roland E. Safety profile of an anti-anginal agent with potassium channel opening activity: an overview. Eur Heart J 1993 Jul; 14 Suppl. B: 48–52PubMedCrossRef
108.
Witchitz S, Darmon JY. Nicorandil safety in the long-term treatment of coronary heart disease. Cardiovasc Drugs Ther 1995 Mar; 9 Suppl. 2: 237–43PubMedCrossRef
109.
Dunn N, Freemantle S, Pearce G, et al. Safety profile of nicorandil: prescription-event monitoring (PEM) study. Pharmacoepidemiol Drug Saf 1999 May; 8(3): 197–205PubMedCrossRef
110.
Reichert S, Antunes A, Trechot P, et al. Major aphthous stomatitis induced by nicorandil. Eur J Dermatol 1997; 7: 132–3
111.
Agbo-Godeau S, Joly P, Lauret P, et al. Association of major aphthous ulcers and nicorandil. Lancet 1998 Nov 14; 352(9140): 1598–9PubMedCrossRef
112.
Gupta A, Morris G. Major aphthous ulcers induced by nicorandil. Age Ageing 2000 Jul; 29(4): 372–3PubMedCrossRef
113.
Shotts RH, Scully C, Avery CM, et al. Nicorandil-induced severe oral ulceration: a newly recognized drug reaction. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 1999 Jun; 87(6): 706–7PubMedCrossRef
114.
Watson A, Al-Ozairi O, Fraser A, et al. Nicorandil associated anal ulceration. Lancet 2002 Aug 17; 360(9332): 546–7PubMedCrossRef
115.
Watson A, Suttie S, Fraser A, et al. Nicorandil associated anal ulceration. Colorectal Dis 2004 Sep; 6(5): 330–1PubMedCrossRef
116.
Toquero L, Briggs CD, Bassuini MM, et al. Anal ulceration associated with Nicorandil: case series and review of the literature. Colorectal Dis 2006 Oct; 8(8): 717–20PubMedCrossRef
117.
Metadata
Title
Use of Nicorandil in Cardiovascular Disease and Its Optimization
Author
Dr Shigeo Horinaka
Publication date
01-06-2011
Publisher
Springer International Publishing
Published in
Drugs / Issue 9/2011
Print ISSN: 0012-6667
Electronic ISSN: 1179-1950
DOI
https://doi.org/10.2165/11592300-000000000-00000

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