Design and rationale of the ARBITER trial (Arterial Biology for the Investigation of the Treatment Effects of Reducing Cholesterol)--a randomized trial comparing the effects of atorvastatin and pravastatin on carotid artery intima-media thickness

Abstract

Background: As a class, statins are remarkably effective in reducing low-density lipoprotein (LDL) cholesterol, and several of these drugs have now been shown to reduce coronary heart disease morbidity and mortality. However, several important controversies in the use of statins remain to be answered by clinical trials. For example, it is controversial whether marked cholesterol reduction to levels below 100 mg/dL would further reduce the incidence of coronary heart disease. Furthermore, concerns about differences among statins for nonlipid effects has raised the concern that the assumption of a class effect is premature until head-to-head clinical trials are completed.

Methods: Arterial Biology for the Investigation for the Treatment Effects of Reducing Cholesterol (ARBITER) is a single-center, randomized, active-controlled study comparing the efficacy of high-dose atorvastatin (80 mg/d) and pravastatin (40 mg/d) in patients being treated for either the primary or secondary prevention of coronary heart disease. This trial will enroll up to 200 patients for the primary end point of the mean change in intima-media thickness of the common carotid artery. This effect will be evaluated over a treatment duration of 12 months. Secondary end points include the effects of statin therapy on inflammatory and hemostatic markers (C-reactive protein and fibrinogen).

Conclusion: ARBITER will provide important data on the role of marked LDL reduction and the "class effect" theory of statin therapy in cardiovascular medicine.