ACEI Post-MI in Diabetics
ABSTRACT & COMMENTARY
Synopsis: Early treatment with ACEI in diabetic acute MI victims reduces mortality and morbidity at six weeks.
Source: Zuanetti G, et al. Circulation 1997;96:4239-4245.
Diabetic patients have a higher mortality following acute myocardial infarction (MI) than non-diabetics. Angiotensin-converting enzyme inhibitors (ACEI) have shown to be valuable in the treatment of acute MI, but, since diabetic patients have more vascular disease, they could cause hypotension and adverse effects in diabetics. Thus, the GISSI-3 investigators retrospectively analyzed their data with respect to a history of diabetes and insulin use. In GISSI-3, suspected acute MI patients were randomized to lisinopril with or without nitrates, begun within 24 hours and continued for six weeks, or no therapy. The primary end point was six-week mortality, and the secondary end point was combined mortality and severe LV dysfunction (EF £ 35% or clinical heart failure). Of the 18,131 patients with known diabetic status, 2790 were diabetic (15%) and most were non-insulin dependent (82%). ACEI treatment decreased mortality at six weeks from 12% in the no therapy group to 9%, which translates to 37 lives saved per 1000 patients treated (P < 0.03). Despite withdrawal of treatment at six weeks, this survival benefit persisted for six months. The results were not different in the insulin-dependent diabetics nor in any other clinical subgroup. The secondary end point was also reduced by ACEI. Hypotension and renal dysfunction were 2-3 times more common in ACEI-treated patients, but there were no differences based upon diabetic status. Zuanetti and associates conclude that early treatment with ACEI in diabetic acute MI victims reduces mortality and morbidity at six weeks.COMMENT BY MICHAEL H. CRAWFORD, MD
The European approach of treating all post-MI patients with ACEI has not been widely followed in the United States for several reasons. The large European studies supporting this practice (GISSI, ISIS) did not have LV function measures on most patients. By contrast, the U.S. studies (SAVE, SOLVD) did, and these studies showed that only those with low EFs benefitted. Also, U.S. physicians have been more concerned with side effects, such as hypotension and renal insufficiency, based upon smaller trials, their own experience, and the message from the large heart failure trials that high doses were needed to see a beneficial effect. Thus, U.S. physicians have tended to be more selective in the application of ACEI post-MI.Since LV function evolves over time post-MI, initial hospital measures may not reflect ultimate values. One approach has been to put all patients on ACEI early post MI and then measure EF in four to eight weeks. Those with a normal EF at that time could have the drug discontinued. This approach makes the most sense with anterior MIs but less so with other MI locations. Also, other patient characteristics may support ACEI use, such as hypertension and possibly diabetes, to prevent renal disease. This study adds to this approach in diabetics because they had a 30% lower mortality on ACEI, whereas the non-diabetics mortality was only reduced 5%.
Although EF was not measured in this study, it is interesting that the diabetic Killip class I patients benefitted more from ACEI than the class II-IV patients. This does not mesh with the SAVE and SOLVD data that suggest that patients with lower EFs do better on ACEI. Perhaps diabetics represent a special risk group in whom ACEI has beneficial effects beyond improved LV performance. Unfortunately, we have no data on glycemic control and the retrospective nature of the study makes the analysis of comorbidities difficult. However, the large population size makes this data compelling and gives us another reason to use ACEI in diabetics post MI—at least for six weeks. Whether they need to be on long-term therapy probably depends upon other issues.
ACE inhibitors post myocardial infarction are most beneficial in patients with:
a. diabetes.
b. left ventricular fraction greater than 50%.
c. renal artery stenosis.
d. systemic hypotension.
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