Dr. Steven Nissen, Cleveland Clinic
In what many cardiologists are describing as a groundbreaking new study, researchers determined that high doses of the statin Crestor® actually reduce the level of plaque that is responsible for hardening arteries.
Over the course of 24 months, 349 patients took 40 milligrams of Crestor (rosuvastatin) a day. At the end of that time, patients taking the statin experienced an average reduction of "bad" low-density lipoprotein (LDLs) of 53 percent and an increase of 15 percent in "good" cholesterol, high-density lipoprotein (HDLs). Most remarkably, patients also experienced a reduction of 7 percent to 9 percent of arterial plaque.
"I think this is actually the first study ever to show that a statin actually reduced the atherosclerotic burden," said Dr. David Zhao, director of the cardiac catheterization lab and head of interventional cardiology at Vanderbilt University Medical Center. "In the past, many studies demonstrated you could slow progression of the atherosclerotic process, but never showed regression. I think it will have a very significant impact in terms of preventing coronary artery disease. Potentially, someone can slowly regress back."
That conclusion is likely to signal a major shift in the way that cardiovascular patients are treated.
"We think that this study has important implications for better understanding the physiopathology and envisaging the optimal treatment of coronary disease," said Dr. Steven Nissen, the principal investigator in the study and a noted cardiologist at the Cleveland Clinic. "It was thought that atheromatous disease was an inexorable process for which treatments could not slow its progression, but our study allows us to be more optimistic. A very aggressive hypolipidemic treatment like that evaluated in ASTEROID (A Study to Evaluate the Effect of Rosuvastatin on Intravascular Ultrasound-Derived Coronary Atheroma Burden) can lead to a regression in this process and thus have very significant clinical benefits."
Plaque is an accumulation of cholesterol, inflammatory cells and fibrous tissue along the arterial walls. If the materials rupture, they can block an artery, provoking a heart attack or stroke.
"We see this as underscoring the benefits of aggressively managing cholesterol levels, both LDL and HDL, to reduce the burden of atherosclerosis," said Dr. Howard Hutchinson, vice president of clinical research for AstraZeneca, which sells the blockbuster anti-cholesterol drug. The results of the study were unveiled at the 55th Annual Scientific Session of the American College of Cardiology, where they received star billing. Nissen is president of the ACC.
Cardiologists seem eager to try it.
"I think there's no doubt that many of us will adopt that quickly," agreed Zhao. But there is one more necessary step in the process, he added. "We need to see whether that reduction of atherosclerosis translated into a better clinical outcome."
That may not take very long.
It's likely that the patients in the most recent study are still being monitored closely, he noted. If so, another 24 months from now should reveal important new data on how Crestor works in terms of better clinical outcomes.
"I have no doubt that it will show that," said Zhao. "Many studies have shown that even slowing down progression can reduce clinical events; stroke, heart attacks and angina. Now we're one step further."
Zhao added, "It's most likely that the people who will benefit the most from this kind of therapy would have mild to moderate plaque buildup. Someone with advanced atherosclerosis wouldn't likely benefit tremendously."
This is just one of a variety of new methods being explored by drug developers. Novartis, for example, has a program to develop D-4F, which was advanced in preclinical stages by Bruin Pharmaceuticals in Los Angeles. Developing work started at UCLA, researchers found that D-4F dramatically reduced plaque in animals. Another half dozen plaque therapies are currently in clinical pipelines.
It's not hard to see what the drug companies are after. In 2004, cholesterol lowering drugs garnered $27 billion in sales, up 12 percent from the year before, according to IMS Health. And a drug company that can demonstrate an ability to go beyond lowering cholesterol and begin undoing decades of plaque buildup will be able to tap into a huge global market.