ISIS 4 provides no grounds for its routine use

Clinical investigators have long pursued the elusive dream of finding a cheap, safe treatment that reduces mortality and morbidity in a common condition. Many investigators had hoped that magnesium given intravenously to patients with acute myocardial infarction might be such a treatment. Were they justified?

Small trials reporting the use of magnesium in acute myocardial infarction have been reported intermittently for 20 years. The rationale for these studies came partly from observations of differences in heart attack rates associated with geographical variations in magnesium in the water supply and partly from laboratory studies showing that magnesium had cardioprotective effects during ischaemia and that myocardial magnesium concentrations were relatively low during acute ischaemia.1

Research on animals has shown that magnesium is a peripheral and coronary vasodilator, has antiarrhythmic effects, decreases reperfusion injury, and has antiplatelet effects in some species.1 The clinical importance of these findings is, however, still uncertain. Experimental studies often do not have the same rigorous design, conduct, and analysis that are now expected from clinical research. Few experimental studies are randomised or blinded. Furthermore, publication bias is likely, with positive results being more likely to be reported than negative ones—especially when the subject is a relatively new hypothesis.

An informal review of the results of the early clinical trials in acute myocardial infarction indicated a trend towards a lower mortality with intravenous magnesium, with this difference being statistically significant in only one trial.2 That trial also found a reduction in arrhythmias. These impressions were subsequently confirmed by a formal metaanalysis.3 The data came, however, from only 1300 patients with a …