Effect of nicorandil on QT dispersion in patients with stable angina pectoris undergoing elective angioplasty
A triple-blind, randomized, placebo-controlled study
Keywords:
Nicorandil, QT-dispersion, Percutaneous Coronary Intervention, Coronary Artery DiseaseAbstract
Background: Nicorandil leads to the relaxation of fine vascular smooth muscle, and thus causes vasodilatation of major epicardial. Also, it has anti-arrhythmic and cardio-protective effects by improving reperfusion, and ultimately leads to a reduction in microvascular damage caused by percutaneous coronary intervention (PCI).
Objective: The aim of this study was to determine the effect of nicorandil on QT interval dispersion (QTd) in patients with stable angina pectoris during elective angioplasty.
Methods: This triple-blind and randomized clinical trial was performed on patients with stable angina pectoris, candidates for elective angiography referred to Imam Reza and Ghaem hospitals in Mashhad, Iran, between January and October 2016. The patients were randomly assigned to one of two groups receiving nicorandil (60 mg as 20 mg before and 40 mg after PCI) and placebo. All the patients underwent electrocardiography 12 hours before and 12 hours after PCI. The values of maximal corrected QT interval (QTc max) and QTd in these intervals, and the levels of changes in the QTd (QTd difference before angiography and after PCI) were compared between the two groups. Data were analyzed statistically using SPSS version 18 software via Chi-square and Independent-samples t-test.
Results: This study was performed on 90 patients (55 males and 35 females) with a mean age of 58.6±10.8 years, on two groups of 45 people. The two groups were matched for age, body mass index, cardiovascular risk factors and baseline testing. The QTd before angiography had no statistically significant difference between the patients of both groups (control: 77.7±17.1 vs. nicorandil: 80.7±14.2 ms; p=0.371). The QTd after PCI in the nicorandil group was lower than the control group (48.1±14.2 vs. 59.2±15.6 ms; p=0.000). The decrease rate in QTd had a statistically significant difference between the two groups (control: 18.9±11.0 vs. nicorandil: 33.5±9.5 ms; p=0.000).
Conclusions: The results of this study showed that oral administration of nicorandil around the PCI could further reduce QTd following PCI, compared to the control group.
Trial registration: The trial was registered at the Iranian Registry of Clinical Trials (http://www.irct.ir) with the
Irct ID: IRCT2016120631159N1
Funding: The authors received no financial support for the research, authorship, and/or publication of this article.
References
Gang Y, Guo X, Crook R, Hnatkova K, Camm A, Malik M. Computerised measurements of QT dispersion
in healthy subjects. Heart. 1998; 80(5): 459-66. doi: 10.1136/hrt.80.5.459. PMID: 9930044, PMCID:
PMC1728844.
Partovi N, Falsoleiman H. Nicorandil in patients with acute coronary syndrome and stable angina
undergoing percutaneous coronary intervention: literature review. Reviews in Clinical Medicine. 2014;
(1): 42-4.
Gholoobi A, Sajjadi SM, Shabestari MM, Eshraghi A, Shamloo AS. The Impact of Remote Ischemic Pre- Conditioning on Contrast-Induced Nephropathy in Patients Undergoing Coronary Angiography and
Angioplasty: A Double-Blind Randomized Clinical Trial. Electron physician. 2015; 7(8): 1557-65. doi:
19082/1557. PMID: 26816582, PMCID: PMC4725407.
Hirohata A, Yamamoto K, Hirose E, Kobayashi Y, Takafuji H, Sano F, et al. Nicorandil prevents
microvascular dysfunction resulting from PCI in patients with stable angina pectoris: a randomised study.
EuroIntervention. 2014; 9(9): 1050-6. doi: 10.4244/EIJV9I9A178. PMID: 24457276.
Kato T, Kamiyama T, Maruyama Y, Tanaka S, Yoshimoto N. Nicorandil, a potent cardioprotective agent,
reduces QT dispersion during coronary angioplasty. Am Heart J. 2001; 141(6): 940-3. doi:
1067/mhj.2001.114369. PMID: 11376307.
Kobayashi Y, Miyata A, Tanno K, Kikushima S, Baba T, Katagiri T. Effects of nicorandil, a potassium
channel opener, on idiopathic ventricular tachycardia. J Am Coll Cardiol. 1998; 32(5): 1377-83. doi:
1016/S0735-1097(98)00372-6. PMID: 9809951.
Ueda H, Hayashi T, Tsumura K, Yoshimaru K, Nakayama Y, Yoshikawa J. Intravenous nicorandil can
reduce QT dispersion and prevent bradyarrhythmia during percutaneous transluminal coronary angioplasty
of the right coronary artery. J Cardiovasc Pharmacol Ther. 2004; 9(3): 179-84. doi:
1177/107424840400900305. PMID: 15378138.
Ueda H, Nakayama Y, Tsumura K, Yoshimaru K, Hayashi T, Yoshikawa J. 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; 20(6): 625-9. PMID: 15152293.
Suematsu Y, Murasato Y, Miura Si, Horiuchi M, Yamamoto T, Takata K, et al. Safety and feasibility of
high-dose administration of nicorandil before reperfusion therapy in acute myocardial infarction.
Cardiovascular intervention and therapeutics. 2013; 28(4): 352-61. doi: 10.1007/s12928-013-0182-z.
PMID: 23625617.
Wu M, Huang Z, Xie H, Zhou Z. Nicorandil in patients with acute myocardial infarction undergoing
primary percutaneous coronary intervention: a systematic review and meta-analysis. PloS one. 2013; 8(10):
e78231. doi: 10.1371/journal.pone.0078231. PMID: 24167609, PMCID: PMC3805586.
Yang J, Zhang J, Cui W, Liu F, Xie R, Yang X, et al. Cardioprotective effects of single oral dose of
nicorandil before selective percutaneous coronary intervention. Anatol J Cardiol. 2015; 15(2): 125-31. doi:
5152/akd.2014.5207. PMID: 25252296.
Jiang J, Li Y, Zhou Y, Li X, Li H, Tang B, et al. Oral nicorandil reduces ischemic attacks in patients with
stable angina: A prospective, multicenter, open-label, randomized, controlled study. Int J Cardiol. 2016;
: 183-7. doi: 10.1016/j.ijcard.2016.08.305. PMID: 27657471.
Day CP, McComb JM, Campbell R. QT dispersion: an indication of arrhythmia risk in patients with long
QT intervals. Br Heart J. 1990; 63(6): 342-4. doi: 10.1136/hrt.63.6.342. PMID: 2375895, PMCID:
PMC1024518.
Malik M, Batchvarov VN. Measurement, interpretation and clinical potential of QT dispersion. J Am Coll
Cardiol. 2000; 36(6): 1749-66. doi: 10.1016/S0735-1097(00)00962-1. PMID: 11092641.
Shah CP, Thakur RK, Reisdorff EJ, Lane E, Aufderheide TP, Hayes OW. QT dispersion may be a useful
adjunct for detection of myocardial infarction in the chest pain center. Am Heart J. 1998; 136(3): 496-8.
doi: 10.1016/S0002-8703(98)70226-1. PMID: 9736143.
Ashikaga T, Nishizaki M, Arita M, Yamawake N, Suzuki M, Hashimoto Y, et al. Effect of dipyridamole on
QT dispersion in vasospastic angina pectoris. The American journal of cardiology. 1999; 84(7): 807-10.
doi: 10.1016/S0002-9149(99)00441-5.
Stolt A, Karila T, Viitasalo M, Mäntysaari M, Kujala UM, Karjalainen J. QT interval and QT dispersion in
endurance athletes and in power athletes using large doses of anabolic steroids. Am J Cardiol. 1999; 84(3):
-6. doi: 10.1016/S0002-9149(99)00299-4. PMID: 10496458.
Brendorp B, Elming H, Jun L, Køber L, Torp‐Pedersen C. Effect of dofetilide on QT dispersion and the
prognostic implications of changes in QT dispersion for patients with congestive heart failure. European
journal of heart failure. 2002; 4(2): 201-6. doi: 10.1016/S1388-9842(01)00235-5.
Macfarlane P, editor. QT dispersion-Lack of discriminating power. Circulation. USA, Philadelphia:
Lippincott Williams & Wilkins; 1998.
Okin PM, Devereux RB, Howard BV, Fabsitz RR, Lee ET, Welty TK. Assessment of QT interval and QT
dispersion for prediction of all-cause and cardiovascular mortality in American Indians the Strong Heart
Study. Circulation. 2000; 101(1): 61-6. doi: 10.1161/01.CIR.101.1.61. PMID: 10618305.
Higham P, Furniss S, Campbell R. QT dispersion and components of the QT interval in ischaemia and
infarction. Br Heart J. 1995; 73(1): 32-6. doi: 10.1136/hrt.73.1.32. PMID: 7888257, PMCID: PMC483752.
Fukuda H, Luo CS, Gu X, Guo LL, Digerness SB, Li J, et al. The effect of K ATP channel activation on
myocardial cationic and energetic status during ischemia and reperfusion: role in cardioprotection. J Mol
Cell Cardiol. 2001; 33(3): 545-60. doi: 10.1006/jmcc.2000.1328. PMID: 11181022.
Light PE, Sabir AA, Allen BG, Walsh MP, French RJ. Protein Kinase C–Induced Changes in the
Stoichiometry of ATP Binding Activate Cardiac ATP-Sensitive K+ Channels A Possible Mechanistic Link
to Ischemic Preconditioning. Circ Res. 1996; 79(3): 399-406. doi: 10.1161/01.RES.79.3.399. PMID:
Rautaharju P, Zhou S, Wong S, Calhoun H, Berenson G, Prineas R, et al. Sex differences in the evolution
of the electrocardiographic QT interval with age. Can J Cardiol. 1992; 8(7): 690-5. PMID: 1422988.
Kassotis J, Costeas C, Bedi AK, Tolat A, Reiffel J. Effects of aging and gender on QT dispersion in an
overtly healthy population. Pacing Clin Electrophysiol. 2000; 23(7): 1121-6. doi: 10.1111/j.1540- 8159.2000.tb00912.x. PMID: 10914368.
Kim JH, Jeong MH, Yun KH, Kim KH, Kang DK, Hong SN, et al. Myocardial protective effects of
nicorandil during percutaneous coronary intervention in patients with unstable angina. Circ J. 2005; 69(3):
-10. doi: 10.1253/circj.69.306. PMID: 15731536.
Published
Issue
Section
License
Copyright (c) 2020 KNOWLEDGE KINGDOM PUBLISHING
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
