Oral Nicorandil in ST Elevation Myocardial Infarction Patients Undergoing Primary Percutaneous Coronary Intervention

Nicorandil

* To study the effects of early oral administration of nicorandil in the setting of PPCI among STEMI patients on early angiographic, electrocardiographic, echocardiographic and hard clinical outcomes. * To assess the possible benefits of nicorandil on myocardial reperfusion through LGE- CMR substudy after 3 months.

Nicorandil is a nicotinamide ester that dilates peripheral and coronary resistance vessels via action on ATP-sensitive potassium channels and possesses a nitrate moiety that promotes systemic venous and coronary vasodilation. As a result of these dual actions, nicorandil reduces preload and afterload and results in an increase in coronary blood flow. In addition to these effects, nicorandil may have cardioprotective actions mediated through the activation of potassium channel . Previous study on the effect of nicorandil on patients with stable angina has shown significant improvement in outcome due to a reduction in major coronary events. Acute occlusion of the coronary artery in the STEMI patient subjects the myocardium supplied by that vessel to acute myocardial ischemia, thereby demarcating the area at risk (AAR) of potential MI, should the acute coronary occlusion be sustained or permanent. If the period of acute myocardial ischemia is prolonged (more than 20 minutes) a wave front of cardiomyocyte death begins in the subendocardium and extends transmurally over time toward the epicardium. The deprivation of oxygen and nutrient supply results in a series of abrupt biochemical and metabolic changes within the myocardium. The absence of oxygen halts oxidative phosphorylation, leading to mitochondrial membrane depolarization, ATP depletion, and inhibition of myocardial contractile function. Ischemia-Reperfusion injury (IRI) is defined as the paradoxical exacerbation of cellular dysfunction and death, following restoration of blood flow to previously ischemic tissues. Reestablishment of blood flow is essential to salvage ischemic tissues. However reperfusion itself paradoxically causes further damage, threatening function and viability of the organ. Early intra-coronary administration of nicorandil has been shown to reduce the damage in the myocardial microcirculation caused by PPCI and the myocardial infarct size in patients with AMI . Nicorandil prior to reperfusion was suggested to improve coronary flow. Furthermore, suppression of ventricular arrhythmia, and improvement of left ventricular function were demonstrated in patients who suffered from AMI and underwent primary PCI. But the definite clinical benefits of nicorandil were not found, which may be due to the small sample size of the selected studies . Compared with intracoronary use alone, the intracoronary and peripheral intravenous use of nicorandil can better improve myocardial microcirculation and short-term prognosis . Nicorandil use prior and post PCI could decrease the occurrence rate of ventricular arrhythmia in STEMI patients undergoing emergent PCI, and this effect might be related with reduced QTd and QTcd post medication . Whether oral nicorandil, which is more widely available and more affordable, would have clinical benefits in terms of measures of reperfusion, and LV recovery post-STEMI, when administered in the early phase of STEMI is still questionable, and warrants further research.

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