Cardioprotective Effects Of Single Oral Dose Of Nicorandil Before Selective Percutaneous Coronary Intervention

Objective: Periprocedural myocardial injury is one of the most importantcomplications of percutaneous coronary intervention (PCI) and is associatedwith adverse outcomes. The slight upregulation of cardiac troponins T and I(cTnI) and MB isoenzyme of creatine kinase (CKMB) could demonstrate thenecrosis of cardiac muscle cells. Also, they were associated with the earlystage and long-term outcomes. Moreover, cTnI and CKMB were positivelyrelated with the incidence of cardiac events (cTnI was more sensitive thanCKMB). It has been reported that a3-fold elevation of cTnI after successfulelective PCI is predictive of future cardiac events, especially the need for earlyrepeat revascularization.According to The Universal Definition Of MyocardialInfarction, percutaneous coronary intervention (PCI) related MI is arbitrarilydefined by elevation of cTn values (>5×99th percentile URL) in patients withnormal baseline values (≤99th percentile URL) or a rise of cTn values>20%if the baseline values are elevated and are stable or falling. Currently, severaldrugs have been used to reduce the incidence of myocardial injury in theperoperative stage, such as statins, intra-coronary administration of betareceptor blocker, nitrate drugs, glycoprotein IIb/IIIa blocker, and adenosine.Nicorandil, presentation of the ATP-sensitive K+(KATP) channel(KATP)openers, is the first clinically available KATP channel opener with a nitrateeffect. Previous studies reported that intravenous and/or intra-coronaryinjection nicorandil could reduce the incidence of peroperative myocardialdamage after PCI. In this study, we aim to investigate the cardioprotectiveeffects of single oral dose of nicorandil nicorandil for the patients withpercutaneous coronary intervention (PCI).Methods: This study was an investigator-initiated, open-labeled, paralleled,randomized trial. One hundred and thirty-eight patients with acute coronary syndrome undergoing PCI from July2011to October2012were randomlydivided into control group (group1, n=47),10mg oral nicorandil group(group2, n=45), and20mg oral nicorandil group (group3, n=46) about2hours before procedure, respectively. Prior to the PCI, enteric coated aspirin(100mg per day), clopidogrel (75mg per day, at least300mg in total), andsubcutaneous injections of low molecular heparin were given to patients. Theinclusion criteria were as follows: patients without medication of nicorandilwithin5days prior to the study; and those with normal levels of cardiactroponin I (cTnI) before PCI. The exclusion criteria were: patients usinggibenclamide and/or glimepiride for the control of blood sugar before the PCI;those with procedure-related complications such as side-branch occlusion,coronary dissection, acute thrombosis in coronary artery, and those withno-reflow; those showed the contraindications of anti-platelet drugs. Cardiactroponin I (cTnI) levels were determined at20~24hours after PCI.Results: No statistical difference was noted in demographics and clinicalvariables among the three groups before PCI except the administration ofstatins. The use of statins was significantly higher in the group1than in thegroup2(P=0.007). While for angiographic features, the rate of using onestent per-patient was significantly higher in the group1than in the group2and group3(P=0.031for group1versus group2, P=0.013for group1versus group3, respectively). There was a significant difference in the rate ofany cTnI elevation among the three groups (group1:36.17%, group2:20.00%, group3:15.22%, P=0.0176). With respect to the frequency of cTnIelevation≥3and5×the upper limit of normal (ULN), there also had statisticaldifference among the three groups (17.02%in group1,8.89%in group2, and4.35%in group3, respectively for cTnI elevation≥3×ULN, P=0.0428;12.77%in group1,6.67%in group2, and2.17%in group3, respectively, forcTnI elevation≥5×ULN, P=0.0487). Logistic regression analysis showedthat LVEF (OR=0.915,95%CI=0.856-0.978, P=0.023) and the use ofnicorandil (OR=0.519,95%CI=0.295-0.912, P=0.009) before PCI wereindependent protective factors of myocardial injury. Conclusions: Single oral dose of nicorandil (10mg,20mg)2hours before thePCI procedure could decrease the incidence of peri-procedure myocardialinjury and PCI-related myocardial infarction.