Geographic variability in patient characteristics, treatment and outcome in an international trial of magnesium in acute myocardial infarction

The interpretation of clinical trials and efforts directed at reducing the worldwide burden of coronary disease must take regional differences into account. This study examined the regional differences in baseline characteristics, treatment, and outcome in patients presenting with ST elevation myocardial infarction (STEMI) who were entered into the Magnesium in Coronaries (MAGIC) trial. MAGIC randomized 6213 patients to standard care with either placebo infusion or infusion of intravenous magnesium sulphate. There was no difference in mortality between these groups. For this analysis, three geographic regions were identified (Region 1=United States and Canada; Region 2=Bulgaria, Georgia, and Russia; Region 3=Austria, Belgium, Chile, Hungary, Israel, the Netherlands, New Zealand, and Venezuela) and compared with respect to baseline characteristics, treatment, and 30-day mortality. Patients in Region 2 had the highest prevalence of adverse risk factors at entry, including history of prior myocardial infarction, heart failure, stroke, and hypertension; anterior location of index acute myocardial infarction; and presence of pulmonary congestion at presentation. Furthermore, Region 2 patients infrequently received reperfusion therapy compared with those in Region 1. Region 3 was intermediate in this regard. Mortality was highest in Region 2, least in Region 1, and intermediate in Region 3. Geographic location, particularly, parts of Eastern Europe, is strongly and independently associated with mortality following STEMI. This geographic variation in mortality confirms prior reports, although adequate explanations continue to be elusive and are beyond the scope of this large simple trial. Future international trials must recognize this variation in design, analysis, and interpretation.