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.
BACKGROUND
Lipid lowering with statins prevents adverse cardiac events. Both lipid-lowering and antioxidant therapies may favorably affect vasomotor function and thereby improve ischemia.


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.
Stone
Peter H
PH
Cardiovascular Division, Brigham & Women's Hospital, Boston, Mass 02115, USA. pstone@partners.org
Lloyd-Jones
Donald M
DM
Kinlay
Scott
S
Frei
Balz
B
Carlson
William
W
Rubenstein
Joel
J
Andrews
Thomas C
TC
Johnstone
Michael
M
Sopko
George
G
Cole
Holly
H
Orav
John
J
Selwyn
Andrew P
AP
Creager
Mark A
MA
D000787:Angina Pectoris / Q000188:drug therapy; D000975:Antioxidants / Q000008:administration & dosage* / Q000493:pharmacokinetics; D001205:Ascorbic Acid / Q000008:administration & dosage / Q000097:blood; D000069059:Atorvastatin; D003324:Coronary Artery Disease / Q000188:drug therapy / Q000628:therapy; D004035:Diet Therapy; D004305:Dose-Response Relationship, Drug; D005080:Exercise Test; D005260:Female; D006538:Heptanoic Acids / Q000008:administration & dosage*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use; D050356:Lipid Metabolism; D008055:Lipids / Q000097:blood; D008077:Lipoproteins, LDL / Q000097:blood; D008297:Male; D017202:Myocardial Ischemia / Q000188:drug therapy* / Q000628:therapy; D011758:Pyrroles / Q000008:administration & dosage*; D014666:Vasomotor System / Q000187:drug effects; D014810:Vitamin E / Q000008:administration & dosage / Q000097:blood
D000975:Antioxidants; D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D008055:Lipids; D008077:Lipoproteins, LDL; D011758:Pyrroles; D014810:Vitamin E; D000069059:Atorvastatin; D001205:Ascorbic Acid