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Indications for ACE Inhibitors in Vascular Disease

Am Fam Physician. 2002 Aug 1;66(3):485-506.

Angiotensin-converting enzyme (ACE) inhibitors are associated with improved survival in patients with congestive heart failure (CHF) and left ventricular systolic dysfunction. Halkin and Keren reviewed the indications for this class of medication.

The Studies of Left Ventricular Dysfunction (SOLVD) trial compared an ACE inhibitor with placebo and found that the risks of acute myocardial infarction (MI) and unstable angina were reduced significantly in patients taking the ACE inhibitor. Rates of acute coronary syndromes were also reduced.

In the Survival and Ventricular Enlargement (SAVE) trial, ACE inhibitors were shown to reduce all-cause mortality in MI survivors and the risk of recurrent infarction. A number of other trials have yielded similar results. The risk of cardiac events that seems to be associated with atherosclerotic plaque rupture is reduced by the use of ACE inhibitors.

ACE inhibitors seem to have an anti-inflammatory effect that restricts vessel wall inflammation. These agents also have antithrombotic properties. The Heart Outcomes Prevention Evaluation (HOPE) trial was terminated prematurely when it was discovered that ramipril-treated patients had significantly lower rates of cardiovascular mortality, cardiac arrest, worsening angina, heart failure, MI, and stroke, compared with those who received placebo. To date, there are no studies showing “definitive evidence” that one ACE inhibitor is preferable to another in terms of efficacy.

ACE inhibitors are standard treatment in patients with reduced systolic left ventricular function, patients who have had an MI, and patients with diabetes who are also hypertensive or nephropathic. After MI, patients who can be projected to receive the most benefit from ACE inhibitors are those with CHF, decreased ejection fraction, and anterior myocardial damage. Almost all patients who receive ACE inhibitors will also be appropriately treated with aspirin. One study found that five-year mortality was lower in patients taking an ACE inhibitor plus aspirin (19 percent) than in those taking an ACE inhibitor alone (27 percent). Similar results were found in patients with CHF who were taking both medicines.

The authors recommend that patients without contraindications to ACE inhibitors should receive this class of medication if they have either established atherosclerosis or diabetes mellitus plus an additional risk factor for cardiovascular disease. Further testing is needed to determine whether angiotensin II receptor antagonists will have the same beneficial effects as ACE inhibitors.

Halkin A, Keren G. Potential indications for angiotensin-converting enzyme inhibitors in atherosclerotic vascular disease. Am J Med. February 1, 2002;112:126–34.


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