Published Online
on April 4, 2005

A more recent version of this article appeared on April 12, 2005

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Submitted on July 21, 2004
Revised on December 20, 2004
Accepted on December 29, 2004

Effect of Intensive Lipid Lowering, With or Without Antioxidant Vitamins, Compared With Moderate Lipid Lowering on Myocardial Ischemia in Patients With Stable Coronary Artery Disease. The Vascular Basis for the Treatment of Myocardial Ischemia Study

Peter H. Stone MD^*, Donald M. Lloyd-Jones MD, SM, Scott Kinlay MD, PhD, Balz Frei PhD, William Carlson MD, PhD, Joel Rubenstein MD, Thomas C. Andrews MD, Michael Johnstone MD, George Sopko MD, Holly Cole BS, John Orav PhD, Andrew P. Selwyn MD, Mark A. Creager MD, for the Vascular Basis Study Group

From Brigham & Women’s Hospital (P.H.S., S.K., W.C., H.C., J.O., A.P.S., M.A.C.); Massachusetts General Hospital, Boston, Mass (D.M.L.-J.); Beth Israel Deaconess Medical Center, Boston, Mass (M.J.); Newton Wellesley Hospital (J.R.), Newton, Mass; University of Texas Southwestern Medical Center, Dallas (T.C.A.); Oregon State University, Corvallis (B.F.); and National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, Md (G.S.).

^* To whom correspondence should be addressed. E-mail: pstone{at}partners.org.

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 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 153 mg/dL at baseline in the 2 atorvastatin groups to 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.

Key words: antioxidants • cholesterol • coronary disease • exercise • vasoconstriction

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