Seelig M S, Elin R J, Antman E M
Department of Nutrition, School of Public Health, University of North Carolina, Chapel Hill, USA.
Can J Cardiol. 1998 May;14(5):745-9.
Many activities of magnesium have justified randomized controlled trials of its role in acute myocardial infarction (AMI), which have shown reduction of short term mortality by 25% to over 50%. The Fourth International Study of Infarct Survival (ISIS-4) megastudy failed to confirm these findings, and, based on analysis of pooled findings, it was concluded that magnesium has no place in treatment of AMI. The fixed effects statistical model employed in ISIS-4 for evaluation of pooled data is inappropriate because the studies were not homogeneous. Among the differences between the earlier studies and the megatrial, the most significant was the time at which magnesium infusions were started relative to the time of reperfusion. Animal studies have shown that magnesium is protective only if present before or at the time of reperfusion. Unlike in earlier trials, in which magnesium infusions were started soon after the ischemic event or simultaneously with a lytic agent, in ISIS-4 magnesium treatment was withheld until after iatrogenic or spontaneous reperfusion occurred. This can explain poor therapeutic results in ISIS-4, but not the hypotension and bradycardia encountered in a minority of patients in that study. Dosage difference alone cannot explain 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 spares magnesium) or the vasodilating oral nitrate in arms of ISIS-4 may have contributed to adverse effects of hypermagnesemia. Also, the very low 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 that magnesium has been shown to be most effective. A large scale study of magnesium in such patients is being started.
镁的许多作用使得针对其在急性心肌梗死（AMI）中作用的随机对照试验具有合理性，这些试验表明短期死亡率降低了25%至超过50%。第四次国际梗死生存研究（ISIS - 4）大型研究未能证实这些发现，并且基于汇总结果的分析得出结论，镁在AMI治疗中没有作用。ISIS - 4中用于评估汇总数据的固定效应统计模型不合适，因为这些研究并非同质。在早期研究与大型试验之间的差异中，最显著的是镁输注开始时间相对于再灌注时间。动物研究表明，镁仅在再灌注之前或之时存在才具有保护作用。与早期试验不同，早期试验中镁输注在缺血事件后不久或与溶栓剂同时开始，而在ISIS - 4中，镁治疗一直推迟到医源性或自发性再灌注发生之后。这可以解释ISIS - 4中较差的治疗结果，但无法解释该研究中少数患者出现的低血压和心动过缓。仅剂量差异无法解释这一点，尽管小型研究中的给药量比ISIS - 4中的少40%至25%，因为第二次莱斯特静脉镁干预试验（LIMIT - 2）中使用的剂量仅略低于ISIS - 4中使用的剂量。在ISIS - 4的分组中，将高剂量镁与血管紧张素转换酶抑制剂（可节省镁）或血管扩张性口服硝酸盐一起使用可能导致了高镁血症的不良反应。此外，ISIS - 4中对照组的极低死亡率表明患者可能处于相对低风险，而镁已被证明在高风险患者中最有效。针对此类患者的镁的大规模研究正在展开。
