EARLY VERSUS DELAYED ANGIOTENSIN-CONVERTING ENZYME-INHIBITION THERAPYIN ACUTE MYOCARDIAL-INFARCTION - THE HEALING AND EARLY AFTERLOAD REDUCING THERAPY TRIAL

Background Although ACE inhibitor therapy has been shown to reduce mor tality in patients with acute myocardial infarction (MI), the optimal dose and the timing of its initiation have not been determined. Method s and Results In a double-blind trial of 352 patients with anterior MI , we compared the safety and effectiveness of early (day 1) versus del ayed (day 14) initiation of the ACE inhibitor ramipril (10 mg) on echo cardiographic measures of left ventricular (LV) area and ejection frac tion (EF). An early, low-dose ramipril (0.625 mg) arm was also evaluat ed. Clinical events did not differ. During the first 14 days, the risk of manifesting a systolic arterial pressure of less than or equal to 90 mmHg was increased in both ramipril groups. LVEF increased in all g roups during this period, but the early, full-dose ramipril group had the greatest improvement in EF (increase: full, 4.9+/-10.0; low, 3.9+/ -8.2%; delayed, 2.4+/-8.8%; P for trend <.05) and was the only group t hat did not demonstrate a significant increase in LV diastolic area. C onclusions The results of the present study demonstrated that in patie nts with anterior MI, the early use of ramipril (titrated to 10 mg) at tenuated LV remodeling and was associated with a prompter recovery of LVEF. The use of low-dose regimen did not prevent hypotension and had only intermediate benefits on LV size and function. The more favorable effects on LV topography of the early use of full-dose ramipril suppo rt the results of the major clinical trials, which have demonstrated a n early survival benefit of ACE inhibition.