In an editorial to be published in the Journal of the American Medical Association online March 13, cardiologists at Johns Hopkins embrace results of a study that shows aggressive use of a cholesterol-lowering drug, rosuvastatin (Crestor), significantly reverses atherosclerosis and its potentially fatal risks. According to the American Heart Association, nearly three-quarters of all deaths from cardiovascular disease are due to atherosclerosis, a condition marked by a long-term deposit of fat and calcium plaques in arteries that nourish the heart. Left untreated, the hardening and narrowing of these vessels create a high risk that blood flow to the heart will be compromised or clots will break off and trigger a stroke.
In the two-year study, conducted at the Cleveland Clinic and other institutions, more than 500 men and women with mild to moderate atherosclerosis were given the maximum-approved dose of 40 milligrams per day of the statin drug, which lowers levels of cholesterol and other fats in the blood. Using ultrasound imaging to measure the degree to which arteries were clogged both before and after treatment, plus blood chemistry testing, researchers found that patients experienced an average 53 percent decline in the so-called bad cholesterol, or LDL, to just over 60 milligrams per deciliter of blood. They also found that HDL cholesterol levels, the so-called good cholesterol that keeps arteries clear, increased on average by 15 percent, to an average 49 milligrams per deciliter of blood. Overall disease progression was slowed by an average of 14 percent, as measured on a disease-specific scale known as percent atheroma volume, with no significant adverse drug effects.
"The study results are very exciting and bound to stir debate and further research," says cardiologist Roger S. Blumenthal, M.D., an associate professor and director of the Ciccarone Preventive Cardiology Center at The Johns Hopkins University School of Medicine and its Heart Institute and lead author of the editorial. "Until now, many scientists did not believe that atherosclerosis could be reversed, even modestly, in people."
Blumenthal cautions that the study's results would have been more convincing if the authors had compared the intense cholesterol-lowering treatment to a more moderate treatment, such as simvastatin (Zocor), another statin drug, which has been shown in large clinical trials to be very effective in reducing cholesterol levels.
He says a definitive answer to why the dramatic reduction in cholesterol leads to the benefits observed in this study will not be ready until results are released from other ongoing clinical trials that are comparing the effects of different dosages and levels of statin reatments.
Editorial co-author Navin K. Kapur, M.D., a clinical research fellow at Hopkins, adds that, "Researchers' next steps have to determine whether these very promising results translate into greater reductions in future heart attacks and strokes."
The new research, which appears in the same issue of JAMA, will be simultaneously presented by other scientists at the annual scientific sessions of the American College of Cardiology taking place in Atlanta, Ga., from March 11 to 14. Results are part of a longer-term study to evaluate the effect of rosuvastatin on intravascular ultrasound-derived coronary atheroma burden, called ASTEROID.
"The results certainly support the idea that we should be even more aggressive in our cholesterol management of people with at least moderate atherosclerosis," says Blumenthal. It would be reasonable, he says, for doctors to aim for lowering bad cholesterol levels to below 70 milligrams per deciliter in people with at least moderate narrowing of the coronary arteries. This objective, he points out, was listed as an optional target in the last update of the National Cholesterol Program Guidelines for people with diabetes and heart disease who had a recent episode of angina, where they experienced chest pain due to decreased blood flow.
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