ACE Inhibition for High-Risk CAD Patients
Abstract & Commentary
Synopsis: One must consider adding ramipril (or possibly 1 of the other ACE inhibitors) to the list of pharmacologic agents now prescribed for most high-risk coronary artery disease patients.
Source: Dagenais GR, et al. Circulation. 2001;104:522-526.
Activation of the renin-angiotensin-aldosterone in the system has been demonstrated to increase the risk of developing acute ischemic heart disease.1 The results of 3 large trials conducted in patients with heart failure or left ventricular dysfunction revealed that the long-term use of an ACE inhibitor reduced cardiac mortality and hospitalizations for congestive heart failure (CHF) and, in addition, decreased the incidence of acute myocardial infarctions (MIs).2-5
The Heart Outcomes Prevention Evaluation (HOPE) study demonstrated significant benefits using an ACE inhibitor, ramipril (Altace), in high-risk persons without known heart failure or left ventricular dysfunction.6 Dagenais and associates, on behalf of the HOPE investigators, expanded the observations of the initial HOPE study by providing greater details on a broad range of coronary events including fatal and nonfatal MIs, types of MIs, unexpected death, unstable angina, coronary revascularization, and worsening or new angina. During the mean follow-up period of 4.5 years, the use of ramipril resulted in a trend toward fewer fatal MIs and unexpected deaths and was associated with a significant reduction in nonfatal MIs. Although ramipril had no effect on hospitalizations for unstable angina, it reduced the risk of worsening and/or new-onset angina and coronary revascularizations in this high-risk cohort of 9297 high-risk men and women over the age of 55 with known previous cardiovascular disease and diabetes.
Comment by Harold L. Karpman, MD, FACC, FACP
Traditionally, ACE inhibitors have been used primarily for control of vascular hypertension, but more recently they have also been used to reduce preload, afterload, and neurohumural factors associated with congestive heart failure. In addition, recently published data1 suggested that ACE inhibition may have a positive effect on the vascular wall by reducing endothelial dysfunction and, therefore, it would appear to be unlikely that only the modest blood-pressure-lowering effect of ramipril noted in the Dagenais et al study was the sole mechanism responsible for reducing the frequency of ischemic events among the HOPE participants. In fact, it is much more likely that the endothelial vascular protective effects of ramipril were responsible for reducing the frequency of ischemic events by virtue of the drug’s beneficial effects on the atherosclerotic process, on thrombogenesis, and/or on the endothelium resulting in the observed decrease in frequency of ischemic events.
From a clinical point of view, multiple studies have clearly demonstrated that high-risk coronary artery disease patients should be treated with antiplatelet agents, beta blockers, and lipid-lowering drugs of the statin variety. It would now appear that one must consider adding ramipril (or possibly 1 of the other ACE inhibitors) to the list of pharmacologic agents now prescribed for most high-risk coronary artery disease patients in order to reduce the risk of developing acute MIs, worsening or new angina, and in order to diminish the frequency of coronary revascularizations.
References
1. Yusuf S. Lonn E. Eur Heart J. 1998;19(suppl J):J36-J44.
2. Yusuf S, et al. Lancet. 1992;340:1173-1178.
3. Pfeffer MA, et al. N Engl J Med. 1992;327:669-677.
4. Torp-Pedersen C, et al. Lancet. 1999;354:9-12.
5. Flather MD, et al. Lancet. 2000;355:1575-1581.
6. HOPE (Heart Outcomes Prevention Evaluation) Study Investigators. N Engl J Med. 2000;342:145-153.
Dr. Karpman, Clinical Professor of Medicine, UCLA School of Medicine, is Associate Editor of Internal Medicine Alert.
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