Magnesium in Coronaries (MAGIC)

BACKGROUND:

The management of patients with acute myocardial infarction (MI) has improved dramatically over the last three decades. Advances in the general coronary care unit environment, treatment with beta blockers, and aggressive attempts at reperfusion have all contributed to a reduction in mortality from acute MI. Large randomized trials have demonstrated that aggressive reperfusion strategies in conjunction with aspirin can reduce mortality in patients with suspected acute MI to an average of 6.5 to 7.5 percent. However, the mortality rate remains high in two particular subgroups of patients: those who do not receive thrombolysis (11.5 to 13 percent) or those over 65 years who do receive thrombolytics (13.5 to 24 percent).

Recently, attention has turned to additional adjunctive pharmacologic treatment with agents such as magnesium, nitrates, and angiotensin converting enzyme inhibitors to determine their potential for reducing mortality further. Of these, magnesium appears to be particularly promising. It is safe, even in the hands of physicians who have no prior experience with it and it is easily administered and readily available in any hospital in the United States. Further, if it has the expected benefit in the high risk groups described, it would become an unusually cost-effective intervention, costing less than $2,500 per year of life saved.

Supplemental administration of magnesium very early after the onset of acute myocardial infarction is supported by abundant data indicating potential cardioprotective effects of magnesium. Magnesium is considered to be "nature's physiologic calcium blocker." This is because it protects myocytes against calcium overload by inhibiting calcium influx which is particularly important at the time of reperfusion. In experimental models of ischemia and reperfusion, agents inhibiting calcium influx improved post-ischemic recovery of mechanical function when given prior to or at the time of reperfusion. On the other hand, little improvement in mechanical function was observed if such agents were given 15-20 minutes after the onset of reperfusion. Reduced serum magnesium may also be responsible for a maladaptive increase in coronary tone and an increased response to vasoconstrictors.

In the setting of acute myocardial infarction, when increased serum magnesium might be beneficial, there is actually a decline in free magnesium. This comes about because of a sharp rise in free fatty acids brought about by catecholamine induced lipolysis at the onset of chest pain, that results in a completing of magnesium in the form of insoluble soaps. Thus, although total body magnesium does not decrease, magnesium available in a free form that is capable of exerting a cardioprotective effect declines. Hence, there is a strong theoretical rationale for supplemental magnesium administration in this setting.