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http://www.acc.org/clinical/guidelines/nov96/1999/jac1716pVa.htm

1999 UPDATED GUIDELINE
(WEB VERSION)

ACC/AHA Guidelines for the Management of Patients With Acute Myocardial Infarction

Magnesium

Recommendations

Class I

None.

Class IIa

1. Correction of documented magnesium (and/or potassium) deficits, especially in patients receiving diuretics before onset of infarction.

2. Episodes of torsades de pointes-type VT associated with a prolonged QT interval should be treated with 1 to 2 g magnesium administered as a bolus over 5 minutes.

Class IIb

1. Magnesium bolus and infusion in high-risk patients such as the elderly and/or those for whom reperfusion therapy is not suitable.

Comment: The available data suggest that mortality reduction may be seen in high-risk patients, provided magnesium therapy is administered soon after onset of symptoms (preferably less than 6 hours). The optimum dose has not been established, but a bolus of 2 g over 5 to 15 minutes followed by an infusion of 18 g over 24 hours has been used with success.

Background

Supplemental administration of magnesium for reducing morbidity and mortality in patients with acute MI is a reasonable avenue to pursue because of abundant data relating magnesium to cardiovascular disease.548 It is the second most abundant intracellular cation and is involved in more than 300 enzymatic processes. Evidence exists that magnesium produces systemic and coronary vasodilatation, possesses antiplatelet activity, suppresses automaticity in partially depolarized cells, and protects myocytes against calcium overload under conditions of ischemia by inhibiting calcium influx especially at the time of reperfusion.548-552

Meta-analyses of the seven randomized trials published between 1984 and 1991 suggest a significant mortality benefit of magnesium (odds ratio 0.44, CI 0.27 to 0.71).553,554 The Second Leicester Intravenous Magnesium Intervention Trial (LIMIT-2) trial555 subsequently reported a 24% reduction in mortality with magnesium treatment (P<.04). The magnesium-treated patients in LIMIT-2 had a 25% lower incidence of CHF in the CCU and a 21% lower rate of ischemic heart disease-related mortality over 4 years, consistent with the hypothesis that magnesium exerts its beneficial effects, at least in part, via a myocardial protective action.555,556

The results of one large trial were negative. The ISIS-4 investigators enrolled 58 050 patients, 29 011 allocated to magnesium, and 29 039 to control. There were 2216 deaths (7.64%) by 35 days in the magnesium group and 2103 deaths (7.24%) in the control group (odds ratio 1.06; CI 0.99 to 1.13), suggesting no mortality benefit of magnesium administration and even the possibility of slight harm.421 When ISIS-4 is added to the preceding randomized trials, meta-analysis indicates no beneficial effect of magnesium. Possible sources of heterogeneity that could explain these differences include:

1. The relatively late administration of magnesium in ISIS-4.557

2. The control group mortality in ISIS-4 was only 7.2%. Regression analyses of the available data predict a null effect of magnesium when the control mortality is about 7% and increasing benefit of magnesium for higher control mortality rates.558

Shechter and colleagues559 recently reported a randomized trial of 194 patients with acute MI unsuitable for thrombolysis. There was a significant reduction in mortality in the magnesium group (4.2% versus 17.3%, P<.01), largely due to a lower incidence of cardiogenic shock and CHF.

An NHLBI-sponsored trial (Magnesium in Coronary Disease [MAGIC]) is planned to further evaluate the role of magnesium in acute MI, especially with early administration before thrombolysis in higher-risk patients.557

© 1999 by the American College of Cardiology and American Heart Association, Inc.


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