2 statin drugs similarly effective in reversing coronary heart disease

Maximum doses of Crestor™ (rosuvastatin) or Lipitor™ (atorvastatin) are similarly effective in reversing the buildup of cholesterol plaques in the coronary artery walls (atherosclerosis) after 24 months of treatment, according to Cleveland Clinic researchers. The extent of reversal of atherosclerosis observed in this trial was unprecedented and was achieved with excellent drug safety.

The SATURN trial results were presented today by lead investigator and Cleveland Clinic researcher, Stephen Nicholls MD PhD., Cardiovascular Director of the Cleveland Clinic Coordinating Center for Clinical Research (C5) at the American Heart Association's Scientific Sessions in Orlando, Fla., and simultaneously published in The New England Journal of Medicine.

The SATURN Trial included 1,039 patients -519 in the atorvastatin group and 520 in the rosuvastatin group. The study used intravascular ultrasound (IVUS) imaging to compare the progression of coronary atherosclerosis after two years of treatment with these two drugs.

For the primary measure of efficacy, IVUS showed a 0.99 percent decrease in plaque burden with atorvastatin and a 1.22 percent decrease with rosuvastatin with no statistically significant differences between the regimens, p=0.17. A secondary endpoint, total plaque burden, did show greater reduction in plaque burden with rosuvastatin that was statistically significant, p=0.01.

The rosuvastatin regimen produced moderately greater lowering of the LDL (bad) cholesterol (62.6 mg/dL vs. atorvastatin 70.2 mg/dL) and a greater increase in HDL (good) cholesterol (50.4 mg/dL vs. atorvastatin 48.6 mg/dL). There were few adverse events observed during the study and no patients experienced serious muscle injury demonstrating that disease regression can be achieved with excellent safety.

Rosuvastatin is an oral drug for lowering blood cholesterol levels. It belongs to a class of drugs called HMG-CoA reductase inhibitors, more commonly referred to as "statins". Other drugs in this class include simvastatin (Zocor), lovastatin (Mevacor), pravastatin (Pravachol), atorvastatin (Lipitor) and fluvastatin (Lescol). These drugs reduce cholesterol levels by inhibiting HMG-CoA reductase, an enzyme that produces cholesterol in the liver. Rosuvastatin and other statins lower blood total cholesterol as well as blood LDL cholesterol levels. LDL cholesterol is the "bad" type of cholesterol that increases the risk of coronary artery disease (atherosclerosis) and heart attacks. Lowering LDL cholesterol levels slows the progression of coronary artery disease and may even reverse it. Statins also increase HDL cholesterol, the "good" type of cholesterol, and reduce triglycerides.

Scientists have discovered that in addition to atherosclerosis, inflammation of the coronary arteries may also contribute to the development of heart attacks. The presence of inflammation can be determined by measuring a chemical in the blood called highly sensitive C-reactive protein (Hs-CRP). Moreover, Hs-CRP can be used to predict the occurrence of heart attacks, strokes and death. Hs-CRP is, in fact, a better predictor of the risk for heart attacks than LDL cholesterol. Scientists have found that statins reduce the level of Hs-CRP in the body, presumably by reducing inflammation in the coronary arteries, and this may be another mechanism through which statins prevent heart attacks, strokes, and death. More research needs to be conducted, however, to confirm the importance of inflammation and the mechanisms through which statins work. Rosuvastatin was approved by the FDA in August 2003.