Researchers found that those who took Zetia failed to shrink buildups in artery walls, while those who took rival drug Niaspan did so significantly.
Ultrasound images revealed Niaspan patients shrank buildups by about 2 percent, but Zetia had no effect on them, even though Zetia did lower bad cholesterol as expected.
Niaspan is a slow release version of the B-vitamin niacin.
A large study last year suggested that the combination pill Vytorin which combines Zetia with a statin, was no more effective than the statin Zocor alone.
Both Zetia and Vytorin are both products of Merck & co. which says it stands behind its drugs.
Niaspan is made by Abbott Laboratories, who sponsored the latest study.