Effect of Very High-Intensity Statin Therapy on Reversal of Coro
Effect of Very High-Intensity Statin Therapy on Reversal of Coronary Atherosclerosis
What is the problem and what is known about it so far?
Atherosclerosis is a progressive disease involving the build up of fatty material, which forms deposits in the arteries. These deposits are called plaque. Risk factors for atherosclerosis include high levels of cholesterol, high blood pressure, smoking, obesity, diabetes, and physical inactivity. It is estimated that some 4.6 million Americans are afflicted with this disease. Atherosclerosis can cause a variety of cardiovascular problems including reduced blood flow, clots, heart attacks, and strokes. The amount of plaque or blockage in arteries can be recognized with a variety of imaging studies (CT scan, ultrasound, arteriography, intravascular ultrasound). Currently treatment to slow progression of disease has focused on reducing elevated cholesterol, primarily with the statin class of drugs and other lipid-reducing agents.
Why did the researchers do this particular study?
Previous studies have shown that statins reduce both the rate of progression of atherosclerosis and risk of cardiovascular events. The study authors wanted to determine if statins simply slow disease progression, or if used at high enough doses, can reverse atherosclerosis.
Who was studied?
This was a multi-center trial in the US, Canada, Western Europe and Australia. 507 patients who had coronary angiography and met several criteria volunteered for this study. Patients were required to have at least one coronary blood vessel 20% blocked. In order to be eligible, patients could not have taken statin medication for more than 3 months in the 12-month period preceding the beginning of this study. Additionally, patients who had received any lipid-lowering medication in the 4 weeks preceding the study underwent a 4-week "wash-out" period before receiving experimental treatment. This means they went 4 weeks without medication so they would not have any left over effects from them. Seventy percent of the patients were male, average age was 58.
How was the study done?
A baseline intravascular ultrasound was performed before treatment. Intravascular ultrasound can be done during cardiac catheterization. The catheter is inserted in a groin or arm artery and snaked up into the arteries supplying the heart muscle. A tiny ultrasound camera on the end of the catheter is used to view the arteries carefully and measure how much blockage there is in each artery. Then, each patient received 40mg/d of rosuvastatin (Crestor), a member of the statin drug class. After 24 months of treatment another intravascular ultrasound was conducted for comparison. Each ultrasound was evaluated for total plaque volume and the percent of the vessel occupied by atherosclerotic plaque by persons unaware of whether the image was made before of after treatment. Blood lipid values were also analyzed.
What did the researchers find?
High-dose statin treatment was found to result in an average of 53% reduction in "bad cholesterol" (LDL-C) in the blood. Additionally, both the total volume of plaque and percent of the vessel occupied by plaque were reduced. Total volume of plaque was reduced in 3/4 of patients studied; 2/3 showed a reduction of the percent of the vessel occupied by plaque, while 1/3 showed an increase in plaque or blockage.
What are the limitations of the study?
The 24-month period of treatment was too brief to determine if high-dose statin therapy is able to reduce the rates of complications and death associated with coronary artery atherosclerosis over the long term. Additionally, there was no control group receiving a placebo or low-dose statin therapy because it was deemed unethical to withhold high-dose treatment. Thus, it is difficult to determine the minimum dose needed.
What are the implications of the study?
Until now atherosclerosis has been viewed as a progressive disease, for which treatment has been aimed at slowing disease progression. However, these results suggest that a high-dose statin treatment may actually reverse atherosclerosis. Since treatment was shown to be reasonably well tolerated (liver and muscle damage may limit statin treatment options in some patients), doctors may suggest more aggressive, high dose treatment with the hopes of reversing the atherosclerotic process.
Summarized by Andrew Boyer, College of Medicine, University of Vermont.
Summarized from "Effects of Very High-Intensity Statin Therapy on Regression of Coronary Atherosclerosis: the ASTEROID trial." Nissen, S.E. et al. Journal of the American Medical Association, April 5, 2006, Vol. 295, No. 13, Pages 1556-65.
