Experimental Drug May Prevent Plaque Buildup

FRIDAY Feb. 20, 2009 -- An experimental drug called A-002 appears effective in preventing atherosclerosis, according to a phase II study that included American and Ukrainian participants.

In atherosclerosis, arteries become blocked and inflamed by a buildup of white blood cells and fatty material, or lipids. Two potentially bioactive fats that can be involved in atherosclerosis are produced when enzymes known as sPLA2 break down particular molecules in the blood and artery walls. The drug A-002 targets three groups of these enzymes that are present in high levels in atherosclerotic lesions.

The 393 people in the study were randomly selected to receive one of four doses of the drug (50, 100, 250 or 500 milligrams) or a placebo twice a day for eight weeks.

Among people taking any dose of A-002, average enzyme levels decreased by 87 percent, compared with a 5 percent drop in the placebo group. The reduction varied by dosage, ranging from an average of 69 percent for those taking 50 mg to 96 percent for people taking 500 mg.

Average levels of low-density lipoprotein cholesterol (the bad type) decreased by 8 percent among people given A-002, compared with a 1.7 percent decline in the placebo group. Concentrations of the inflammatory marker C-reactive protein fell by 56 percent among people taking the drug and 25 percent among those given the placebo.

The findings appear in this week's issue of The Lancet.

"Our study demonstrates that sPLA2 inhibition produces favorable changes in plasma lipids, oxidized LDL and inflammatory markers, and the magnitude of these changes was larger in statin-treated patients," Dr. Robert S. Rosenson, a specialist in cardiovascular medicine at the University of Michigan Medical School, and colleagues wrote.

Though Rosenson said that further study is needed to determine "the effects of sPLA2 inhibition on reducing atherosclerosis progression and cardiovascular events," the study's conclusion suggested that "the reductions in sPLA2 concentration suggest that A-002 might be an effective anti-atherosclerotic agent."

In an accompanying editorial in The Lancet, Dr. Marshall A. Corson, of the University of Washington/Harborview Medical Center in Seattle, noted that a number of other seemingly promising anti-inflammatory or antioxidant therapies eventually proved ineffective or harmful.

This "suggests that challenges might lie ahead for sPLA2 inhibitors," Corson wrote. "These difficulties could increase the regulatory hurdles that need to be cleared for these, or other, novel anti-atherosclerotic therapies."

More information

The U.S. National Heart, Lung, and Blood Institute has more about atherosclerosis.

Posted: February 2009


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