Drug Fails to Slow Progression of Atherosclerosis
TUESDAY, March 17 -- A drug that blocks an enzyme involved in the accumulation of cholesterol does not reduce the progression of atherosclerosis, thickening and stiffening of the arteries, but increases the risk of major cardiovascular events, according to an international study.
Researchers assessed the safety and efficacy of the drug pactimibe, which inhibits an enzyme known as ACAT, in 892 people with a family history of high cholesterol, which is associated with an increased risk of atherosclerosis. The participants, from 40 clinics in the United States, Canada, Europe, South Africa and Israel, were randomly selected to take either 100 milligrams a day of pactimibe or a placebo, in addition to standard lipid-lowering therapy.
The researchers assessed the participants' atherosclerosis at the start of the study and 12, 18 and 24 months later using ultrasound to measure carotid intima-media thickness (CIMT), a measurement of the thickness of the inner wall of a major artery. Increasing thickness indicates increasing plaque in the artery.
After six months, levels of "bad" low-density lipoprotein (LDL) cholesterol had increased by 7.3 percent among people taking pactimibe and by 1.4 percent among those taking the placebo. This increase disappeared after participants stopped taking the drug.
There was no difference between the two groups in progression of maximum CIMT, but average CIMT progressed significantly in the pactimibe group within one year, compared with minor CIMT progression in the placebo group, the study found.
Compared with people in the placebo group, those in the pactimibe group suffered more serious events (10 percent vs. 7.7 percent) and more cardiovascular events (6.3 percent vs. 3.4 percent) and had a higher rate for the composite of cardiovascular death, heart attack and stroke (2.3 percent vs. 0.2 percent).
Dr. Marijn C. Meuwese, of the Academic Medical Center in Amsterdam, The Netherlands, and colleagues wrote that in people with a family history of cholesterol, "pactimibe had no effect on atherosclerosis as assessed by changes in maximum CIMT compared with placebo but was associated with an increase in mean CIMT as well as increased incidence of major cardiovascular events."
The findings from this and previous studies lessen "the promise and further development of this class of drugs (ACAT inhibitors) for cardiovascular prevention," they concluded.
The study is in the March 18 issue of the Journal of the American Medical Association.
The U.S. National Heart, Lung, and Blood Institute has more about atherosclerosis.
Posted: March 2009
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