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The relationship of chronic pre-event statin use with coronary disease severity at the time of presentation with a first acute ST-elevation myocardial infarction (STEMI) is unknown. A retrospective review was performed of consecutive patients presenting with STEMI and without a prior history of vascular disease, divided into those whom had been treated with statins before presentation (n=50) and those whom were not pretreated (n=231). Patients pretreated with statins were more likely to have left main (24.0% vs 8.3%; P=.001) or 3-vessel disease (44.0% vs 25.1%; P=.007) vs untreated patients. After matching for risk factors, a trend toward higher likelihood of 3-vessel disease persisted in the statin pretreatment group (47.6% vs 28.6%; P=.07). Significantly lower peak troponin-I levels (87.8 mg/dL vs 134.5 mg/dL; P=.006) were found in patients pretreated with statins, suggesting that statin pretreatment is protective in patients with STEMI despite the presence of greater disease burden. This finding supports the concept that statin therapy alters the natural history of coronary artery disease development leading to a first STEMI and is cardioprotective in those patients who experience a first STEMI.