Post-MI ACE Inhibitor Use
August 1, 1997 4 minutes read
Post-MI ACE Inhibitor Use
ABSTRACT & COMMENTARY
Synopsis: In patients with anterior myocardial infarction, early full-dose ACE inhibitor therapy was associated with greater recovery of left ventricular function than low-dose ACE inhibitor.
Source: Pfeffer MA, et al. Circulation 1997;95: 2643-2651.
Although the benefits of angiotensin con- verting enzyme (ACE) inhibition in post myocardial infarction (MI) patients is well established, the size and timing of the first dose is unclear. Thus, the results of the Healing and Early Afterload Reducing Trial (HEART) are of interest. The 352 patients with anterior MI were randomized to early (day 1) vs. late (day 14) initiation of the ACE inhibitor ramipril. The early-dose group included those given low-dose ramipril (0.625 mg/d) and those titrated up to 10 mg/d over a few days. Therapy was continued for 14 days. Then, the placebo patients were switched to full-dose ramipril. The study was terminated at 90 days. Pre-therapy patients (78%) were in Killup’s Class I, and the average ejection fraction (EF) was 52%. Systolic blood pressure declined over the first 72 hours in all groups, but more so in the ramipril treated groupsone quarter to one-third of whom had at least one systolic blood pressure (< 90 mmHg vs. 15% of the placebo group [P = 0.01]). Early major cardiac events were not different in the four groups. EF increased during the first 14 days in all groups, but the increase was greatest in the early full-dose group (5%) vs. low-dose (4%) or placebo (2%, P < 0.05). Also, those with the lowest EF and the most dyssynergy showed the greatest improvement with ACE inhibitor therapy. During later therapy (14-90 days), clinical events were not different between the high- and low-dose groups, and further gains in EF were only seen in the group started on ramipril after day 14. The investigators conclude that in patients with anterior MI, early full-dose ACE inhibitor therapy was associated with greater recovery of left ventricular function than low- dose ACE inhibitor. Also, low-dose ACE inhibitor did not prevent hypotension.
COMMENT BY MICHAEL H. CRAWFORD, MD
These results are consistent with the results of concurrently performed large clinical trials (GISSI-3 and ISIS-4) that showed a long-term survival benefit of early ACE inhibitor therapy after MI and suggest that the mechanism is the prevention of ventricular remodeling. It is now clear that substantial ventricular enlargement can occur early after MI, and ACE inhibitor therapy during this period can reduce this consequence of MI. Apparently, the increase in hypotensive episodes and their potentially deleterious effects are offset by the prevention of remodeling early after MI. Thus, this and other trials support early full-dose therapy for those likely to benefit from this therapy.
The results are different from those of CONSENSUS-II, which failed to show remodeling benefit using early intravenous ACE inhibitor (enalapril). Since considerable hypotension was observed in this study with active drug, it was assumed that this was the mitigating factor. Thus, hypotension should be avoided if possible, but fear of hypotension should not prevent the early use of this beneficial approach.
The large clinical trials (GISSI, ISIS) treated all MI patients with ACE inhibitors, whereas the smaller trials (SAVE, AIRE) have focused on patients with anterior MI or reduced left ventricular function, where a larger effect is likely to be observed. Whether all MI patients benefit enough to be treated with ACE inhibitors early or only certain subgroups should be treated (large, anterior MIs, heart failure) is still unclear, but all of these studies have shown greater benefit in those with large or anterior MIs and those with left ventricular dysfunction.
Another issue is what to do about other recommended treatment such as beta blockers and nitrates that may contribute to hypotension. These trials did not prohibit standard therapy, and the majority of patients in this trial were on beta blockers (69%) and nitrates (85%). Although care to prevent hypotension is prudent, these agents do not seem to be contraindicated if ACE inhibitor therapy is used. Also, the role of an open artery is unclear, yet this occurrence also tends to improve long-term left ventricular function. In addition, about 9% of the study patients had angioplasty or bypass surgery early, which may have influenced the results.
These results and those of other studies suggest that ACE inhibitors should be started early (day 1) after acute MI and titrated to full dose as rapidly as possible without inducing prolonged hypotension. Other therapy such as beta blockers, nitrates and revascularization should not be withheld for appropriate patients. This approach is especially beneficial in patients with anterior or large MIs and those associated with poor left ventricular function. The risk benefit ratio will have to be carefully weighed in others before starting therapy.
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