[Modulation of the beta-adrenergic system during acute myocardial infarction: rationale for a new clinical trial].

Acute myocardial infarction is caused by sudden coronary artery occlusion. Persistent ischemia results in necrosis of the myocardial tissue supplied by the occluded vessel. It has recently been shown that the final size of the infarct is a major predictor of future clinical events, and is, therefore, used as a surrogate outcome in clinical trials. Moreover, it has become clear that the duration of ischemia in the main determinant of the success of myocardial salvage (i.e. of non-necrotic at-risk myocardium). In addition to minimizing the time between symptom onset and reperfusion, there is considerable interest in finding therapies that can further limit the size of the infarction (i.e. cardioprotective therapies) and they are the focus of numerous clinical studies. Oral β-blockade within the first few hours of an AMI is a class-IA indication in clinical practice guidelines. However, early intravenous β-blockade, even before coronary artery reperfusion, is not routinely recommended. Preclinical research has demonstrated that the selectiveβ1-blocker metoprolol is able to reduce the infarct size only when administered before coronary artery reperfusion, which indicates that its cardioprotective properties are secondary to its ability to reduce reperfusion injury. In addition, retrospective studies of AMI suggest that starting intravenous β-blockade early has clinical benefits (i.e. lower mortality and better recovery of left ventricular contractility) in patients without contraindications. Our general hypothesis is that early administration of metoprolol (i.e. intravenously before reperfusion) results in smaller infarcts than administering the drug orally after reperfusion. The Effect of METOprolol in CARDioproteCtioN during an acute myocardial InfarCtion (METOCARD-CNIC) trial will test this hypothesis in patients with ST-segment elevation AMI.