The implications of these observations are that, to prevent calcium overload of reperfused myocytes, a loading dose of magnesium should be administered before thrombolytic therapy and during the period when spontaneous reperfusion is most likely to occur in patients not receiving thrombolytics. The design of ISIS-4 did not permit these conditions to be met. Further, prior studies suggest that the low risk profile that characterized the ISIS-4 patients would have been likely to preclude obtaining much additional benefit. The results of the small trial reported by Schechter et al strongly support the view that high risk MI patients benefit from early treatment with magnesium infusion. However, definitive proof requires the larger sample size proposed in MAGIC.