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, Donald M. Lloyd-Jones, Scott Kinlay, Balz Frei, William Carlson, Joel Rubenstein, Thomas C. Andrews, Michael Johnstone, George Sopko, Holly Cole, John Orav, Andrew P. Selwyn, Mark A. Creager

Research output: Contribution to journalArticle

45 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1747-1755
Number of pages9
JournalCirculation
Volume111
Issue number14
DOIs
StatePublished - Apr 12 2005

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Vitamins
Myocardial Ischemia
Blood Vessels
Coronary Artery Disease
Ischemia
Antioxidants
Lipids
Ambulatory Monitoring
Lovastatin
Electrocardiography
Exercise Test
Therapeutics
Ascorbic Acid
Dilatation
Exercise
Diet
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Control Groups
Brachial Artery
Vitamin E

Keywords

  • Antioxidants
  • Cholesterol
  • Coronary disease
  • Exercise
  • Vasoconstriction

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

Cite this

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. / Stone, Peter H.; Lloyd-Jones, Donald M.; Kinlay, Scott; Frei, Balz; Carlson, William; Rubenstein, Joel; Andrews, Thomas C.; Johnstone, Michael; Sopko, George; Cole, Holly; Orav, John; Selwyn, Andrew P.; Creager, Mark A.

In: Circulation, Vol. 111, No. 14, 12.04.2005, p. 1747-1755.

Research output: Contribution to journalArticle

Stone, Peter H. ; Lloyd-Jones, Donald M. ; Kinlay, Scott ; Frei, Balz ; Carlson, William ; Rubenstein, Joel ; Andrews, Thomas C. ; Johnstone, Michael ; Sopko, George ; Cole, Holly ; Orav, John ; Selwyn, Andrew P. ; Creager, Mark A. / 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. In: Circulation. 2005 ; Vol. 111, No. 14. pp. 1747-1755.
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abstract = "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.",
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TY - JOUR

T1 - 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

T2 - The vascular basis for the treatment of myocardial ischemia study

AU - Stone, Peter H.

AU - Lloyd-Jones, Donald M.

AU - Kinlay, Scott

AU - Frei, Balz

AU - Carlson, William

AU - Rubenstein, Joel

AU - Andrews, Thomas C.

AU - Johnstone, Michael

AU - Sopko, George

AU - Cole, Holly

AU - Orav, John

AU - Selwyn, Andrew P.

AU - Creager, Mark A.

PY - 2005/4/12

Y1 - 2005/4/12

N2 - 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.

AB - 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.

KW - Antioxidants

KW - Cholesterol

KW - Coronary disease

KW - Exercise

KW - Vasoconstriction

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JO - Circulation

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