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Abstract & Commentary
By Michael H. Crawford, MD, Professor of Medicine, Chief of Cardiology, University of California, San Francisco. Dr. Crawford is on the speaker's bureau for Pfizer. This article originally appeared in the July 2010 Clinical Cardiology Alert. It was peer reviewed by Ethan Weiss, MD. Dr. Weiss is Assistant Professor of Medicine, Division of Cardiology and CVRI, University of California, San Francisco; he reports no financial relationships relevant to this field of study.
Source: Milonas C, et al. Effect of angiotensin-converting enzyme inhibition on one-year mortality and frequency of repeat acute myocardial infarction in patients with acute myocardial infarction. Am J Cardiol. 2010;105:1229-1234.
The use of angiotensin converting enzyme (ACE) inhibitors in all acute myocardial infarction (MI) patients is controversial. Thus, these investigators from the Register of Information and Knowledge about Swedish Heart Intensive Care Admissions (RIKS-HIA) examined the association between ACE inhibitor therapy and mortality in unselected patients with acute MI. This registry started in 1995 and includes almost all patients admitted to Swedish hospitals with acute coronary syndromes until 2005. The patient population for this study is 105,224 patients with acute MI who were not treated with ACE inhibitors on admission. They were followed for one year for mortality and repeat admission for acute MI. Two groups were compared: those put on ACE inhibitors at discharge and those not. Since there were differences in baseline characteristics between the two groups, a propensity score was calculated for each patient and used to adjust for baseline characteristics and treatment.
Results: Thirty-seven percent of the patients received ACE inhibitors at discharge; 30% in 1995, increasing to 43% in 2005. The unadjusted one-year mortality rate was less in those treated with ACE inhibitors as compared to those not (10.6% vs. 12.1%, p < 0.001). After adjustment, the risk ratio for mortality in those on treatment was 24% less (RR = 0.76, 95% CI 0.73-0.80). The benefit was largely confined to those with a history of current heart failure. Also, in those where it was measured, the ACE inhibitor benefit was greater as the glomerular filtration rate and ejection fraction decreased. Readmission for acute MI was decreased 7% when adjusted (RR = 0.93, 95% CI 0.9-0.96), with the major effect seen in those with ST elevation MI and systolic left ventricular dysfunction (LV). The authors concluded that ACE-inhibitor treatment prior to discharge of unselected acute MI patients was associated with reduced one-year mortality, but mainly in those with heart failure and renal dysfunction. Also, there was a small reduction in recurrent MI mainly in patients with STEMI and LV dysfunction.
Current guidelines recommend ACE inhibitors for acute MI with preserved LV function, but there is little data to support this practice. Previous trials have shown benefits largely in high-risk patients such as those with heart failure or reduced LV function. The guidelines are based upon data from patients with stable CAD treated over many years. So even though this is not a randomized trial, the results are of interest because unselected patients with acute MI, not treated on admission with ACE inhibitors, were analyzed based upon whether or not they received ACE inhibitors at discharge. This study represents the largest observational study of this issue, so propensity scoring adjustments for differing baseline characteristics could be made with adequate power. The results showed that ACE inhibitors reduce mortality mainly in patients with heart failure and renal dysfunction, and they reduce recurrent MI largely in patients with STEMI and reduced LV function. If I were revising the guidelines for post-MI care, I would recommend ACE inhibitors for acute MI patients if they had STEMI, LV dysfunction, heart failure, or renal dysfunction (IIa). ACE inhibitor treatment for all acute MIs would be IIb. Of course, ACE inhibitors could be used for other indications such as hypertension.
There are some caveats to this study. Propensity score adjustments may not account for all differences between groups. We do not have data on the actual ACE inhibitor the patients were on or the dose. Not all ACE inhibitors may be the same, and prior studies have shown variable effects depending on dose. This study was completed before the widespread use of angiotensin receptor blocking drugs (ARB). They accounted for < 3% of prescriptions for drugs targeting the renin-angiotensin system in this study. Also, we do not know the effect of the drugs on blood pressure in this study, which could be an important consideration.
The benefits observed in those with renal dysfunction are interesting because we often do not start ACE inhibitors if there is renal dysfunction. Also, ACE inhibitors are indicated in diabetics to prevent renal damage. Of those discharged on ACE inhibitors, 22% had diabetes. But, in subgroup analyses, diabetes did not influence the results of the study. Less than 2% of patients in the study had renal failure, but the number with renal dysfunction is not given.
Partially because the study started in 1995, only about one-third had coronary angiography and one-quarter revascularization. About half the patients were on statins. Thus, more aggressive therapy for acute MI could alter the results of this study. The major message I take from this study is that ACE inhibitors or ARBs should be reserved for those following acute MI who have definite indications such as heart failure, LV dysfunction, hypertension, or diabetes, and should be more strongly considered in those with renal dysfunction.