FOR RELEASE:4 p.m. ET, MondayApril 2, 2001
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American Heart Association journal report:Beta-blocker slows wall thickening of neck artery in healthy people
DALLAS, April 3 -- For the first time in humans, researchers show that a beta-blocker drug slows the progression of artery-clogging plaque in the carotid arteries of healthy people, according to a report in today's Circulation: Journal of the American Heart Association.
The three-year study found that low doses (25 mg. once daily) of the beta-blocker drug metoprolol CR/XL slows the rate of progression of atherosclerosis by 40 percent in healthy, symptom-free people who have plaque build-up in their carotid (neck) arteries. Beta-blockers are generally used to treat high blood pressure and heart failure and to prevent recurrent heart attack.
"This is the first randomized trial to show that metoprolol CR/XL has an anti-atherosclerotic effect in humans," says lead author Bo Hedblad, M.D., Ph.D., associate professor of Malmo University Hospital, Malmo, Sweden. "Although studies in animals have shown some beta-blockers have an anti-atherosclerotic effect, until now, there has been no direct evidence of the effect in humans."
The carotid arteries supply blood to the brain. The narrowing of these arteries by plaque is called atherosclerosis. The more advanced the atherosclerosis, the greater the chance one of the carotid arteries will become blocked by plaque or a blood clot, causing a stroke. If a blood vessel leading to the heart is blocked, a heart attack can occur.
Hedblad notes that studies on preventing first and recurrent cardiovascular events already have shown some that beta-blockers reduce the risk for heart attacks, stroke and death. This research indicates that the central nervous system, which some beta-blockers act upon, may play an important role in accelerating atherosclerosis development.
Earlier animal studies have indicated psycho-social stress as being an important factor for atherosclerosis development, with a beta-blocker being protective.
In the randomized, double-blind, placebo-controlled, trial known as Beta-Blocker Cholesterol-Lowering Asymptomatic Plaque Study or BCAPS, researchers examined the effects of low-dose, controlled release metoprolol succinate and the cholesterol-lowering statin drug fluvastatin on the thickening of the inner lining of the carotid artery. Statins have previously been shown to reduce carotid artery wall thickening.
The study participants were drawn from an urban, white, Swedish population participating in the Malmo Diet and Cancer Study. These 793 individuals (435 were women) ranged in age from 49 to 70 years and had plaque in the carotid artery, but no symptoms of carotid artery disease.
Participants were randomly assigned to one of four groups: those receiving metoprolol CR/XL, those taking fluvastatin, a group taking a combination of metoprolol CR/XL and fluvastatin, and a fourth group on placebo.
The first participant was enrolled in the study in November 1994, and the 36-month treatment period was completed for all participants by February 1999.
Ultrasound images of the participants' carotid arteries were taken at enrollment, 18 months, and 36 months. Progression of artery thickening at both 18 and 36 months was reduced by metroprolol CR/XL. Incidence of cardiovascular events, heart attacks and stroke also tended to be lower in those on the beta-blocker.
The study findings suggest that the beta-blocker may have a beneficial effect on the early stages of atherosclerosis development, according to Hedblad. He says the low dose of metoprolol CR/XL used in the study is substantially less than the amount used to treat high blood pressure. For that reason, Hedblad says a higher dose of metoprolol CR/XL may have more effect on atherosclerosis.
"Further experimental studies need to be conducted to understand the mechanisms of the anti-atherosclerotic effect of metoprolol CR/XL," Hedblad says. He also says further studies are needed before clinical implications can be drawn about the use of the beta-blocker in atherosclerosis, although the potential population that could benefit is large.
While statins' anti-atherosclerotic effects already have been demonstrated in many trials, BCAPS shows that fluvastatin reduced the rate of progression of thickening of the inner lining of carotid arteries by 75 percent, he says.
Hedblad also notes the two drugs worked on different sites in the carotid artery. While fluvastatin works on the site of the common carotid artery, he says, metoprolol CR/XL works at the point where the artery forks in two different directions. There was no indication of any interaction between the two drugs.
Co-authors include Goran Berglund, M.D., Ph.D.; John Wikstrand, M.D., Ph.D.; Lars Janzon, M.D., Ph.D.; and Hans Wedel, Ph.D.
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NR01-1274 (Circ/Hedblad)
Media advisory: Dr. Hedblad can be reached at 46-40-336305, by fax at 46-40-336215 or by e-mail at [email protected]. Dr. Berglund can be reached at 46-40-332301, by fax at 46-40-923272 or by e-mail at [email protected] (Please do not publish contact information.)
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