Principal Findings:

Despite dissemination of acute myocardial infarction (MI) guidelines, reperfusion (thrombolysis or PTCA), aspirin, beta blockers, and ACE inhibitors are underused in clinical practice. The MITRA investigators examined "maximal individual therapy" using all 4 of these strategies as recommended unless contraindicated.

MITRA began with a 6-month pilot period during which time physicians were instructed to continue their standard treatment approach to the acute MI patient (n=1,313). Subsequently, clinicians were asked to optimize their therapy for acute MI patients seen between 2/95 and 1/96 (n=2,688) or between 2/96 and 1/97 (n=2,062). In both 1-year phases, clinicians were obligated to document why each therapy was given or withheld during treatment of the acute infarction. Baseline characteristics were similar for these unselected series of acute MI patients.

Use of all study treatments increased significantly from the pilot phase to the end of the second 1-year study (all <0.001 except for any reperfusion therapy which was p=0.003). The most dramatic increase in clinical use was for angiotensin-converting enzyme (ACE) inhibitors, which jumped from 16% to 63%. Beta-blocker use nearly doubled (33% to 62%), with aspirin (88% to 96%) and reperfusion therapy (55% to 60%) showing comparatively more modest increases. The increase in reperfusion was attributable almost entirely to an increased use of angioplasty as primary treatment.

Better adherence to acute MI guidelines led to a significant decrease in in-hospital mortality during the second 1-year study phase compared to placebo (13.1% vs. 16.3%, p=0.005), a relative reduction of 19.6%.

Increasing the amount of therapy given to patients might increase hospital complications, but this did not appear to be the case. Indeed, there were significant reductions in in-hospital reinfarction (6% to 4%, p=0.01) and heart failure (defined as New York Heart Association Class II to IV) (10% to 7%, p=0.01), with a trend toward fewer in-hospital strokes (2.5% to 1.6%, p=0.08). There was no change in postinfarction angina.

Corresponding to the improvement in heart failure, left ventricular (LV) function based on pre-discharge echocardiography (in 85% of patients) also improved, with significantly more patients showing normal LV function during the last phase of the study compared to the pilot phase.