Evidence supports high-dose over low-dose atorvastatin in stable coronary heart disease

Atorvastatin 80 mg/d is associated with better cardiovascular outcomes than atorvastatin 10 mg/d in patients with stable coronary heart disease (CHD), according to John LaRosa, MD, who presented the results of the Treating to New Targets (TNT) study at the ACC Annual Scientific Session 2005.

The study is the latest to demonstrate a clinical advantage of an aggressive lipid-lowering regimen compared with a moderate regimen in patients with various manifestations of CHD.

Although the reduction in cardiovascular risk with high- vs low-dose atorvastatin was "very robust," new guideline recommendations for lowering low-density lipoprotein (LDL) cholesterol for patients with stable CHD should await completion of other studies in progress, said Dr LaRosa, president, State University of New York Downstate Medical Center, Brooklyn, NY.

The risk of achieving the primary end point-a composite of death from CHD, nonfatal myocardial infarction, resuscitation from cardiac arrest, or fatal or nonfatal stroke-was reduced by 22% (P=.0002) in patients randomized to high-dose vs low-dose atorvastatin. The outcome of stroke was reduced by 25% in the group randomized to 80 mg/d (P=.02).

No significant difference in mortality was observed between the 2 groups, which was attributed to an insufficient total number of deaths. "We cannot with 10,000 people even answer the issue of mortality, and this is going to be a problem from now on in clinical trials in this area," said Dr LaRosa. "We have to make the assumption... that lowering LDL does lower the total mortality rate."

Both treatments were well tolerated. The incidence of persistent elevations in liver enzyme levels was 0.2% in the group randomized to 10 mg/d and 1.2% in the group randomized to 80 mg/d of atorvastatin (P<.001), "which is a fraction of the rate in other statin trials," Dr LaRosa said.

The incidence of persistent elevations in creatine kinase levels or complaints of myalgia were not different between the 2 groups. Five cases of rhabdomyolysis were reported, none of which the investigators attributed to the study drug.

Proposed changes in the target levels of LDL cholesterol for patients with stable CHD should await the results of additional studies in which aggressive and moderate lipid-lowering are compared; those studies are expected to be completed soon, Dr LaRosa said.

"We would be on firmer ground if we waited," he said. "We already have an option to go to 70 [mg/dL]."

In 2004, the Adult Treatment Panel (ATP) of the National Cholesterol Education Program (NCEP) issued an update to the ATP III guidelines in which an option to achieve a more aggressive LDL cholesterol level-70 mg/dL-was offered at the discretion of the treating physician when treating high-risk patients.