By Ashley Starkweather, B.S. and Asher Kimchi M.D.

Brooklyn, NY - Intensive statin therapy was proven to reduce the risk of cardiovascular events in patients with established coronary artery disease and a current LDL level of less than 130mg/dl. The results of the double-blind, randomized trial were published by John C. LaRosa, M.D., et. al, from the State University of New York Health Science Center as an early release on March 8, 2005 in the New England Journal of Medicine. The findings were presented at this year’s American College of Cardiology meeting in Orlando, Florida. 

While the value of reducing LDL cholesterol levels in preventing major cardiovascular events has been well documented, the issue has been raised as to what optimal treatment targets should be. Prior to this study, the value in reducing LDL levels below 100mg/dl in patients with coronary artery disease has not been clearly proven. 

Between July 1998 and December 1999 a total of 10,001 patients with clinically evident coronary artery disease and LDL cholesterol levels of less than 130mg/dl were randomly assigned to double-blind therapy with either 10mg or 80mg atorvastatin per day. Eligible patients were men and women ages 35 to 75 years old who had clinically evident coronary artery disease (CAD), defined by one or more of the following: previous myocardial infarction, previous or current angina with evidence of atherosclerotic CAD, and history of revascularization. 

Mean LDL levels during the study were 77mg/dl in the 80mg atorvastatin treatment group, and 101mg/dl in the 10mg atorvastatin group.  

The primary efficacy endpoint was the occurrence of a major cardiovascular event, defined as death from CAD, nonfatal myocardial infarction, resuscitation after cardiac arrest, or fatal or nonfatal stroke. A total of 434 patients in the group given 80mg of atorvastatin and 548 patients in the 10mg group. This represented a 2.2 percent absolute reduction in the 80mg group, with a 22 percent relative reduction in the primary outcome (hazard ratio 0.78, 95 percent confidence interval 0.69 to 0.89, P<0.001). As compared with patients given 10mg of atorvastatin, patients in the 80mg group had significant reductions in the risk of a major coronary event, any coronary event, cerebrovascular events, hospitalization with a primary diagnosis of congestive heart failure, and any cardiovascular event. 

Furthermore, the risk of death from any cause did not differ significantly between the two drug regimens (hazard ratio 1.01, 95 percent confidence interval 0.85 to 1.19, P=0.92). Adverse events related to treatment occurred in 8.1 percent of patients on 80mg of atorvastatin, and in 5.8 percent of patients on 10mg (P<0.001). These events included persistent elevation in alanine aminotransferase, aspartate aminotransferase, or both, and a few rare cases of rhabdomyolysis. There were no persistent elevations in creatine kinase. 

The results of this trial indicate that intensive therapy with 80mg of atorvastatin to reduce LDL levels below 100mg/dl provides significant clinical benefits in patients with established coronary artery disease when compared to therapy at the 10mg dose, with the only significant side effect being an elevation in aminotransferase levels and occasional cases of rhabdomyolysis. 

Co-authors: Scott M. Grundy, M.D., Ph.D., David D. Waters, M.D., Charles Shear, Ph.D., Philip Barter, M.D., Ph.D., Jean-Charles Fruchart, Pharm.D., Ph.D., Antonio M. Gotto, M.D., D.Phil., Heiner Greten, M.D., John J.P. Kastelein, M.D., James Shepherd, M.D., Nanette K. Wenger, M.D.