1 . A low control group mortality rate. The control group mortality in ISIS-4 was only 7.2 percent. This was probably the result of the combination of extensive use of thrombolysis (70 percent of patients) and antiplatelet agents (94 percent of patients) combined with the enrollment of intrinsically low-risk patients (only 28 percent were over 70 years of age, 17 percent had a history of a prior MI, 14 percent had clinical congestive heart failure (CHF), and 2 percent had systolic blood pressure (SBP) <100 mm Hg). Incremental mortality reducing effects of magnesium are difficult to detect against a low background control mortality rate. The inability of ISIS 4 to detect any overall benefit of magnesium also apply to specific subgroups such as the 17,325 patients who did not receive thrombolytics. ISIS 4 had less than 60 percent power to detect even a 10 percent reduction observed in the 9.3 percent control mortality in this subgroup. A detailed analysis relating the mortality rate in the control group and the treatment effect of magnesium observed in the clinical trials published before ISIS-4 shows clearly that the benefit of magnesium therapy increases as the control group mortality increases. Using this relationship, it was predicted that trials with a control group mortality rate of about 7 percent would show no benefit of magnesium therapy, precisely the result observed in ISIS-4. Of note, the LIMIT-2 trial observed a control group mortality of 10.3 percent that was reduced to 7.8 percent with magnesium. The ISIS-4 control group mortality was thus below that of the magnesium treated group in LIMIT-2.