Intravenous magnesium therapy in acute myocardial infarction.
OBJECTIVE
To review the methods and summarize the findings of clinical trials evaluating the use of intravenous magnesium (Mg2+) in acute myocardial infarction (AMI); to discuss serum Mg2+ in AMI and the potential mechanisms by which intravenous Mg2+ may be effective. Tables are used extensively to provide detailed information about the various trials.


METHODS
A MEDLINE search was used to identify pertinent literature. Additional references were obtained from the articles retrieved from that search.


METHODS
Studies randomized and/or placebo-controlled were selected for review. Additional relevant citations were used in the introductory material and discussion.


METHODS
There were surprisingly few large, placebo-controlled trials. All clinical trials available at the time of publication were reviewed. Only eight trials enrolled sufficient numbers of patients and/or were of adequate design to make meaningful interpretations. The description of the methods and results of these articles are the basis of this review. Although additional controlled studies with more subjects are needed, the results to date form a foundation from which to make inferences regarding the utility of this therapeutic modality.


RESULTS
Intravenous Mg2+ has been demonstrated, albeit inconclusively, to reduce immediate and long-term morbidity and mortality when given in the immediate postinfarction period. Six of the eight controlled trials discussed report a decrease in the overall incidence of arrhythmia or in the frequency of arrhythmia requiring treatment. Four of the eight reported statistical significance. Five of the six trials evaluating mortality reported a decrease in the mortality rate from intravenous Mg2+ administered post-MI. Four of the five reported statistical significance. The favorable effect of intravenous Mg2+ on the mortality rate appears to occur in the first 30 days post-MI and is maintained through at least one year. The effects appear to be independent of concurrent therapy and do not appear to relate to baseline serum Mg2+ concentrations. Intravenous Mg2+ appears to be safe and well tolerated. Flushing, hypotension, and atrioventricular (AV) node conduction abnormalities occur on occasion and seem related to the rate of administration. The exact dosage in this setting remains to be determined.


CONCLUSIONS
Additional, well-designed, multicenter, controlled trials evaluating intravenous Mg2+ in AMI are needed. The pending Fourth International Study of Infarct Survival, with an anticipated 400,000 subjects, should clarify a number of unresolved issues regarding this therapy. Based on the information available to date, however, intravenous Mg2+ as a significant therapeutic modality for AMI shows promise. Pending further investigation, however, it should be avoided in patients with significant sinoatrial or AV conduction disturbances.
Hampton
E M
EM
Pharmacokinetic Dosing and Research Unit, Department of Veterans Affairs Medical Center, Oklahoma City, OK 73104.
Whang
D D
DD
Whang
R
R
D001145:Arrhythmias, Cardiac / Q000188:drug therapy; D002986:Clinical Trials as Topic; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D007262:Infusions, Intravenous; D008274:Magnesium / Q000008:administration & dosage / Q000627:therapeutic use*; D009203:Myocardial Infarction / Q000188:drug therapy*; D009206:Myocardium / Q000473:pathology; D009336:Necrosis / Q000188:drug therapy; D016032:Randomized Controlled Trials as Topic
D008274:Magnesium