BACKGROUND: Lipid lowering with statins prevents adverse cardiac events. Both 
lipid-lowering and antioxidant therapies may favorably affect vasomotor function 
and thereby improve ischemia.
METHODS AND RESULTS: In a randomized, double-blind, placebo-controlled trial, 
300 patients with stable coronary disease, a positive exercise treadmill test, 
48-hour ambulatory ECG with > or =1 episode of ischemia, and fasting total 
cholesterol of 180 to 250 mg/dL were assigned to 1-year treatment with intensive 
atorvastatin to reduce LDL to <80 mg/dL (n=96), intensive atorvastatin to reduce 
LDL to <80 mg/dL plus antioxidant vitamins C (1000 mg/d) and E (800 mg/d) 
(n=101), or diet and low-dose lovastatin, if needed, to reduce LDL to <130 mg/dL 
(n=103; control group). Ischemia end points, including ambulatory ECG monitoring 
and exercise treadmill testing, and endothelial assessment using brachial artery 
flow-mediated dilation were obtained at baseline and at 6 and 12 months. 
Baseline characteristics were similar in all groups. LDL decreased from 
approximately 153 mg/dL at baseline in the 2 atorvastatin groups to 
approximately 83 mg/dL at 12 months (each P<0.0001) and from 147 to 120 mg/dL in 
the control group (P<0.0001). During ambulatory ECG monitoring, mean number of 
ischemic episodes per 48 hours decreased 31% to 61% in each group (each P<0.001; 
P=0.15 across groups), without a change in daily heart rate activity. Mean 
duration of ischemia for 48 hours decreased 26% to 62% in each group (each 
P<0.001; P=0.06 across groups). Mean exercise duration to 1-mm ST-segment 
depression significantly increased in each group, but total exercise duration 
and mean sum of maximum ST depression were unchanged. Angina frequency decreased 
in each group. There was no incremental effect of supplemental vitamins C and E 
on any ischemia outcome. Flow-mediated dilation studies indicated no meaningful 
changes.
CONCLUSIONS: Intensive lipid lowering with atorvastatin to an LDL level of 80 
mg/dL, with or without antioxidant vitamins, does not provide any further 
benefits in ambulatory ischemia, exercise time to onset of ischemia, and angina 
frequency than moderate lipid lowering with diet and low-dose lovastatin to an 
LDL level of <120 mg/dL.