MAGNESIUM IN ACUTE MYOCARDIAL-INFARCTION - STILL AN OPEN QUESTION

Many activities of magnesium have justified randomized con trolled tri als of its role in acute myocardial infarction (AMI), which have shown reduction of short term mortality by 25% to over 50%. The Fourth Inte rnational Study of Infarct Survival (ISIS-4) megastudy failed to confi rm these findings, and, based on analysis of pooled findings, it was c oncluded that magnesium has no place in treatment of AMI. The fixed ef fects statistical model employed in ISIS-4 for evaluation of pooled da ta is inappropriate because the studies were not homogeneous. Among th e differences between the earlier studies and the megatrial, the most significant was the time at which magnesium infusions were started rel ative to the time of reperfusion. Animal studies have shown that magne sium is protective only if present before or at the time of reperfusio n. Unlike in earlier trials, in which magnesium infusions were started soon after the ischemic event or simultaneously with a lyric agent, i n ISIS-4 magnesium treatment was withheld until after iatrogenic or sp ontaneous reperfusion occured. This can explain poor therapeutic resul ts in ISIS-4, but not the hypotension and bradycardia encountered in a minority of patients in that study. Dosage difference alone cannot ex plain this, even though the amounts given in the small studies were 40 % to 25% less than that in ISIS-4, because the dose used in the Second Leicester Intravenous Magnesium Intervention Trial (LIMIT-2) was only slightly lower than that used in ISIS-4. Administration of high dose magnesium with an angiotensin converting enzyme inhibitor (which spare s magnesium) or the vasodilating oral nitrate in arms of ISIS-4 may ha ve contributed to adverse effects of hypermagnesemia. Also, the very l ow mortality rate of controls in ISIS-4 suggests that the patients may have been at relatively low risk, and it is in high risk patients tha t magnesium has been shown to be most effective. A large scale study o f magnesium in such patients is being started.