Looking for a way to slow down atherosclerosis, researchers have examined the effects of blocking the action of an enzyme called acyl:cholesterol-acyltransferase (ACAT) that has been identified as a major culprit in the formation of atherosclerotic plaques.

ACAT activity in the intestine is required for the absorption of dietary cholesterol and for the formation of the cholesteryl esters found in atherosclerotic plaques. Treatment of experimental animals with drugs that block the enzyme decreased the formation of atherosclerotic plaques.

These findings contributed to the expectation that treating people with drugs that block the action of ACAT would diminish the size of their arterial plaques. However, clinical trials of patients who were given two different inhibitors of ACAT have yielded disappointing results.

The first trial used the inhibitor avasimibe for two years in 509 patients with known coronary disease. The second gave another inhibitor, pactimibe, for 18 months to 408 patients with known coronary disease.

There was no reduction in the volume of atherosclerotic plaque in either study. In fact, among participants in the second trial, plaque volume increased at sites of large plaques, especially in patients with diabetes. LDL cholesterol levels rose slightly in the first study, but there were no significant changes in blood lipids in the second trial.

The negative results of these two trials almost certainly mark the end of any hope that this seemingly promising form of treatment can reduce the risk of cardiovascular events resulting from atherosclerosis.