Vascular Basis for the Treatment of Myocardial Ischemia Study - Vascular Basis for the Treatment of Myocardial Ischemia Study
The goal of the study was to evaluate the use of intensive lipid lowering, with or without antioxidant vitamins, compared with moderate lipid lowering on ambulatory and exercise-induced ischemia in patients with stable coronary disease and moderately elevated cholesterol.
Patients Screened: 597
Patients Enrolled: 300
Mean Follow Up: 12 months
Mean Patient Age: Mean age 64 years
Mean Ejection Fraction: Mean baseline ejection fraction of 56%
Age <85 years, fasting total cholesterol of 180-250 mg/dl, objective evidence of coronary disease, exercise-induced ST-segment depression of 1.0 mm, and one episode of reversible ST depression of 1.0 mm during 48-hour ambulatory ECG monitoring of routine activities
Acute coronary syndrome within one month of study entry, coronary revascularization procedure within six months of study entry, congestive heart failure greater than New York Heart Association class III, significant valvular heart disease, cigarette smoking within two months of study entry, and a resting 12-lead ECG that was not interpretable to detect the presence of ischemia
Change from baseline to 12 months in: (1) number and duration of ischemic episodes on the ambulatory ECG, (2) exercise time to 1.0 mm ST-segment depression, and (3) flow-mediated vasodilation of the brachial artery
Patients were removed from all long-acting antianginal medications for at least 48 hours before baseline studies, including exercise treadmill test (ETT), flow-mediated dilation assessment of brachial artery, and ambulatory ECG monitoring. Patients were randomized to one-year treatment with intensive atorvastatin to reduce low-density lipoprotein (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). Patients underwent repeat ETT, brachial artery flow-mediated dilation, and ECG monitoring at 6 and 12 months.
Median atorvastatin dose was 80 mg daily. Lovastatin was used in 91% of patients in the control group, with a median dose of 5 mg daily. Baseline characteristics were well matched between treatment groups, with an average total cholesterol of 223-230 mg/dl and an average LDL of 141-151 mg/dl.
At six months, LDL decreased to 85 mg/dl in the two intensive atorvastatin groups and to 123 mg/dl in the control group (p<0.001 for each vs. control). At 12 months, number of ischemic episodes per 48 hours decreased by 1.6 in the atorvastatin group, by 1.2 in the atorvastatin plus antioxidant group, and by 3.1 in the control group (each p<0.001 vs. baseline; p=0.15 for between group change), but there was no change in daily heart rate activity.
Additionally, the mean duration of ischemia for 48 hours decreased in all groups compared to baseline (p<0.01), but without a significant difference between groups (35.1, 19.2, and 63.9 minutes, respectively; p=0.06 between groups). Similar results were observed for median exercise duration to 1 mm ST-segment depression (5.9, 6.0, and 6.9 minutes, respectively; p=0.52 between groups).
There was no difference in change in total exercise duration (0.02, -0.09, and -0.08 minutes, respectively; p=0.51) or change in mean sum of maximum ST depression (-0.26, -0.09, and -0.61 mm; p=0.72). Flow-mediated dilation studies showed no difference between groups, with mean endothelium-dependent dilation change from baseline of -0.1% for atorvastatin, -1.0% for atorvastatin plus antioxidants, and -0.9% for control (p=0.35). There was no difference in clinical events (8% for atorvastatin, 7% for atorvastatin plus antioxidants, and 5% for control; p=0.62).
Among patients with stable coronary artery disease and moderately elevated cholesterol, intensive lipid lowering with atorvastatin to an LDL of 85 mg/dl, with or without antioxidant vitamins, was not associated with benefits in ambulatory ischemia, exercise time to onset of ischemia, or endothelium-dependent vasodilation compared with moderate lipid lowering with diet and low-dose lovastatin to an LDL level of 123 mg/dl. Addition of antioxidant vitamins did not add incremental benefit to any of the lipid or ischemic measures compared with atorvastatin alone.
While the present study showed no change in ischemic parameters in the setting of stable coronary disease, it is unknown if similar results would be shown in the setting of acute coronary syndrome. The much larger PROVE IT-TIMI 22 trial demonstrated a reduction in clinical events with intensive lipid lowering in the setting of acute coronary syndrome.
Stone PH, Lloyd-Jones DM, Kinlay S, et al. 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. Circulation 2005;111:1747-55.
Presented at ACC 2004 Scientific Sessions by Peter H Stone, MD.
Clinical Topics: Acute Coronary Syndromes, Dyslipidemia, Heart Failure and Cardiomyopathies, Prevention, Atherosclerotic Disease (CAD/PAD), Homozygous Familial Hypercholesterolemia, Lipid Metabolism, Nonstatins, Novel Agents, Statins, Diet
Keywords: Coronary Artery Disease, Acute Coronary Syndrome, Vitamin E, Vasodilation, Lovastatin, Hyperlipidemias, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Heptanoic Acids, Electrocardiography, Hypercholesterolemia, Heart Rate, Pyrroles, Fasting, Exercise Test
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