[1] Next I’d like to call on Masafumi Kitakaze from Osaka in Japan to present his trial, “Large-Scale Trial Using Atrial Natriuretic Peptide or Nicorandil as an Adjunct to Percutaneous Coronary Intervention for ST-Segment Elevation Acute Myocardial Infarction.” Thank you Dr. Jacobs and Dr. Fox. Ladies and gentleman, at my presentation I have nothing to disclose. [2] First of all, I would like to express my sincere thanks to the president of the American Heart Association and the organizing committee for inviting me to present the investigation of the effect of either carperitide or Nicorandil on acute myocardial infarction. We named this trial JWIND, showing here. [3] Recently, reperfusion therapies have been standardized in patients with acute myocardial infarction and diminished the incidents of in-hospital death from 20-30% to 5-10% over for the latest 30 years. However, the incidence of…however, the increased survival rate result in the increased incidence of cardiovascular event after myocardial infarction in the modern era. There are three strategies to decrease the incidence of cardiovascular event following myocardial infarction. These are prevention of MI occurrence…MI recurrence, inhibition of LV remodeling after MI, and reduction of infarct size. The former two events are well treated by the drugs, however the appropriate drugs to reduce infarct size have not been found until now. Although several drugs are tested, most clinical trials using an adjunctive drug for AMI targeting the reduction of infarct size has been proved to either negative or balanced. [4] Recently, many researchers have found that either carperitide of Nicorandil reduce infarct size. The upper panels show that either carperitide or Nicorandil administered upon reperfusion reduced the infract size in canine experimental model in our laboratory. Furthermore, the lower panels show that either carperitide or Nicorandil administered upon reperfusion improved ventricular function at the chronic stage following a MI in human studies of small sampling size. These we found indicated that either carperitide or Nicorandil is promising for the reduction of infarct size and attenuation of cardiovascular event in patients of AMI. We tested this idea. [5] Therefore, the aim of the present study is to evaluate the effect of either carperitide of Nicorandil on infarct size. Chronic left ventricular dysfunction and subsequent cardiovascular outcomes in patients with acute myocardial infarction using large scale clinical trials. [6] The study subject is a patient with AMI. We tested the patient with carperitide or its solvent for the carperitide study and Nicorandil or its solvent for the Nicorandil study. The dose and regimen of administration of either carperitide of Nicorandil are exactly the same as in the previous clinical trials. The study design is prospective, randomized, blinded, controlled trials. The study period is December, 2001 to August 2006. [7] The inclusion criteria are: 1. New onset attack. 2. 20 to 79 years old. 3. Chest pain of more than 30 minutes. 4. 0.1 mV ST segment elevation in two ECG leads. 5. Admission to the hospital within 12 hours of symptom onset. The exclusion criteria are also shown in the lower part of the slide here. [8] The primary endpoints are: 1. Infarct size estimated by the area under curve of creatinine kinase. 2. Chronic left ventricular function assessed by left ventriculography. And secondary endpoints are: 1. All cause mortality. 2. Cardiovascular event. 3. Incidence of reperfusion injury. [9] Since previous single center studies demonstrated that intravenous administered carperitide or Nicorandil decreased the CK variable by 20%, to detect the satisfactory significant differences with 80% power and with alpha equals 0.05, a total of 600 patients is required when 10% dropout patients are estimated in each study. All analyses were performed according to the intention to treat. We analyzed Sigma CK and ejection fraction. Since these data are log-normally distributed, the data are log transformed and then analyzed. We also obtained the estimate of the event rate using Kaplan-Meier method. The relative risk was obtained by Cox model that provides a time-averaged hazard ratio. [10] This shows a flow chart of the present study. In all, 1,216 patients were screened. For the study of carperitide, 34 patients were excluded out of 602 patients because they were not AMI such as ... myopathy, although they met the entry criteria, or they declined ... . They were randomly assigned to the placebo group of 292 patients and a carperitide group of 277 patients. For the study of Nicorandil, 68 patients were excluded out of 613 patients and they were randomly assigned to the placebo group of 269 patients and the Nicorandil group of 276 patients. All of the assigned patients were evaluated. [11] This shows the study organization and participating hospitals. We have the steering committee, the data center, and the coordinating center to promote and evaluate the present study. We also sent the independent data safety and the monitoring committee to survey the unfavorable events. This committee has a right to decide to continue or discontinue the present study. Sixty-five hospitals with coronary care unit in Japan participated in either the carperitide trial of 27 hospitals or the Nicorandil trial of 38 hospitals. Since the hospital that participated in one of the two studies was not allowed to participate in the other study, these two studies were considered as two independent clinical trials. [12] This shows the baseline characteristics of the patients assigned in each group. There are no significant differences of age, gender, or BMI between the two groups in each study. Recurrence of hypertension, diabetes mellitus, hyperlipidemia, or smoking was comparable between the two groups in each study. Almost all of the patients were classified in KILLIP IV and 40% of patients had pre-angina. Mean elapse time was within four hours and 40-60% of the culprit artery was LAD. Now, I will show the data of the primary endpoint. [13] This shows the infarct size assessed by the area under the curve of the creatinine kinase. In the left panel, carperitide significantly reduced infarct size by 14.7%. However, as is shown in the right panel, Nicorandil did not reduce infarct size. [14] Furthermore, left ventricular function was significantly improved in the carperitide group compared to the placebo group. On the other hand, we found that Nicorandil did not improve ejection fraction. [15] Since carperitide significantly reduced infarct size, we further examined the factors that effect carperitide mediated limitation of infarct size. None of the factors effected the carperitide mediated limitation of infarct size. I will show the result of the secondary endpoint. [16] This shows the incidence of reperfusion injury. Carperitide significantly reduced the incidence of reperfusion injury by 25.9%. However, Nicorandil did not affect the incidence of reperfusion injury. [17] This shows the all cause mortality and the composite endpoints. There was no difference in all cause mortality when we used either Nicorandil or carperitide. Both carperitide and Nicorandil, shown in the red line, decreased the extent of the composite endpoints, although there are no significant differences, suggesting that both carperitide and Nicorandil may mediate better clinical outcomes at the chronic stage around here and here. [18] Indeed carperitide significantly decreased the incidence of either cardiac death and/or heart failure by 73.3%. On the other hand, Nicorandil also decreases the incidence by 22.1% but without significant results. [19] On the other hand, there are ... point of Nicorandil. First of all, the left panel shows that although Nicorandil administration throughout the study increased the extent of improvement of ejection fraction within acute and acute and chronic phases. The right panel shows that the incidence of revascularization for the non-culprit lesions is reduced by the Nicorandil treatment. [20] We summarize the present study as follows: 1. We investigated the effect of either carperitide of Nicorandil on infarct size, chronic left ventricular function, reperfusion injury, and cardiovascular events in patients with AMI. 2. The infusion of carperitide reduced infarct size in patients with AMI. 3. Carperitide increased chronic left ventricular ejection fraction by 5.1%. 4. Carperitide reduced the incidence of reperfusion injury. 5. Carperitide decreased and Nicorandil marginally decreased the incidence of cardiac death and rehospitalization due to heart failure. 6. On the other hand, the intravenous administration of Nicorandil did not reduce infarct size, reperfusion injury, or the incidence of cardiovascular events. 7. When Nicorandil was administered orally in the chronic phase, left ventricular function was improved and the development of new coronary lesions in non-culprit artery was significantly reduced. [21] Therefore, we summarize that, we conclude that we firstly demonstrated that carperitide reduced infarct size and reperfusion injury, and improved the left ventricular function followed by the reduction…reduced incidence of cardiac death and heart failure in patients with their first AMI as an adjunct therapy on top of reperfusion therapy. Nicorandil may provide additional cardiovascular protection. Following oral treatment of Nicorandil, improved left ventricular function and inhibited the incidence of revascularization of non-culprit lesions in AMI patients. The current study opens new era of adjunctive therapy in patients with AMI. Lastly, I thank the participant hospitals and patients and many of my colleagues, especially Dr. ... Kim, ... for their devoted work. We thank the Ministry of Health, Labor, and Welfare Japan, and Japan Cardiovascular Research Foundation for the support of these trials. Thank you very much for your kind attention. [22]