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We retrospectively studied the outcomes of patients with acute myocardial infarction who were treated with either direct angioplasty or thrombolytics followed by angioplasty. Two patient cohorts were analyzed: a previously reported (in regard to short-term follow-up) group of 371 patients who now have long-term follow-up (mean, 3.4 years) of survival and event-free survival and a second group of 202 patients who have been treated since publication of our initial data. Both 1-year and 2-year survival were significantly better (p = 0.01 and 0.02, respectively) in the group that was treated with thrombolytics first. Event-free survival (i.e., no myocardial infarction, coronary artery bypass graft surgery, repeat angioplasty) was better overall (p < 0.01) for the group that was treated with thrombolytics first. The more recently treated group of patients also showed benefit in regard to both survival (p = 0.002) and event-free survival (p < 0.01) over a short-term follow-up period (mean, 39 weeks) for patients who were treated initially with thrombolytics as compared with those who were treated with direct angioplasty. Although the initial cohort was very similar to the treatment groups except for age (mean age for the direct angioplasty group was 62 +/- 12 years vs 57 +/- 11 years for thrombolytics first group, (p = 0.0002), several differences existed in the more recent treatment groups. The patients who were more recently treated with direct angioplasty were older, had lower mean ejection fraction, had more extensive coronary artery disease, and were more likely to have had prior coronary artery bypass grafting.(ABSTRACT TRUNCATED AT 250 WORDS)