People with known heart disease or a major risk factor, such as diabetes, are counseled to reduce their low-density lipoprotein (LDL) cholesterol ("bad" cholesterol) below 100 milligrams/deciliter (mg/dL) of blood. The goal for patients whose only risk factor is high cholesterol is usually below 130 mg/dL. Statin drugs are commonly used to lower total and LDL cholesterol.
There has been some question recently, however, whether more aggressive LDL lowering would confer an even greater benefit, says lead author Allen J. Taylor, M.D., director of cardiovascular research at Walter Reed Army Medical Center in Washington, D.C.
In addition, there is a question of whether factors besides cholesterol-lowering figure into the overall benefit from statin therapy. Besides affecting cholesterol, statins may also affect levels of inflammation or the degree of artery thickening.
"This is the first comparison of two statin drugs in a general population that looked at more than their cholesterol-lowering abilities," says Taylor.
Researchers recruited 161 patients (average age 60, 71 percent men) who were candidates for statin therapy. About half had known cardiovascular disease. Of these patients, 138 completed the study in which they received either 40 milligrams (mg) of the natural drug pravastatin, or 80 mg of relatively new synthetic statin called atorvastatin.
After 12 months, those receiving pravastatin treatment had a 27.5 percent drop in their LDL cholesterol compared to a 48.5 percent reduction in LDL for people treated with the higher dose of atorvastatin. The pravastatin group's LDL was reduced to 110 mg/dL while the atorvastatin group's LDL level was 76 mg/dL.
Researchers used ultrasound to compare the thickness of the carotid arteries (major arteries in the neck that supply blood to the brain) before treatment, after six months, and after one year of therapy. The amount of plaque in the carotid arteries is considered a good indicator of the amount of atherosclerosis throughout the body.
The researchers found that many patients had a net decrease in carotid artery thickness – 54 percent of atorvastatin patients and 39 percent of pravastatin patients.
Patients who received moderate treatment with pravastatin showed a slight progression in the thickness of the atherosclerosis in their carotid arteries (from an average of .615 mm at baseline to an average of .640 mm thickness at 12 months). Those who received atorvastatin treatment had a decrease (from an average of .625 mm to an average of .591 mm).
"Atherosclerosis is a progressive disease that takes years to develop and continues to get worse over time unless treated," Taylor explains. "Previous studies found that patients in whom plaque stabilized – or stopped progressing – had the lowest risk of heart attacks and other cardiovascular disease problems. In general, past studies have shown that regression is uncommon."
"We need to carefully define at what point lower LDL values have the greatest benefit in lowering the risk of heart disease. This study would suggest that LDL values much lower than 100 mg/dL appears better than a value of around 100," he says.
In an accompanying editorial, Prediman K. Shah, M.D., director of the division of cardiology and atherosclerosis research center at Cedars Sinai Medical Center in Los Angeles, Calif., says, "The data provided by Taylor are of potential interest and could have significant implications for clinical practice. However, before we conclude that more LDL-lowering means less atherosclerosis progression or clinical events, more in depth research is necessary."
Shah points to several large scale trials that are measuring the effect of moderate vs. aggressive cholesterol lowering on coronary plaque and cardiac events that should provide additional valuable information in the near future.
Co-authors include Steven M. Kent, M.D.; Patrick J. Flaherty, D.O.; Louis C. Coyle, D.O.; Thor T. Markwood M.D.; and Marina N. Vernalis, D.O.
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