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Study Assessing Goals in the Elderly - SAGE
Description:
The goal of the trial was to evaluate intensive statin therapy using atorvastatin 80 mg/d compared with moderate statin therapy using pravastatin 40 mg/d among older patients with stable coronary artery disease (CAD).
Study Design
Study Design:
Patients Screened: 4,852
Patients Enrolled: 893
Mean Follow Up: 12 months
Mean Patient Age: Mean age 73 years
Female: 30
Patient Populations:
Age 65 to 85 years with a documented history of CAD, baseline LDL cholesterol levels between 100 mg/dl and 250 mg/dl, and ≥1 episode of myocardial ischemia with a total duration of ≥3 minutes during 48-hour ambulatory ECG monitoring at the screening visit
Primary Endpoints:
Absolute change from baseline in total duration of ischemia at month 12
Secondary Endpoints:
Absolute change in the total duration of myocardial ischemia on 48-hour Holter monitor from baseline to 3 months; percent change in the total duration of myocardial ischemia on 48-hour Holter monitor from baseline to 3 and 12 months; absolute and percent change in the number of ischemic episodes on 48-hour Holter monitor from baseline to 3 and 12 months; percent change in the ischemic burden on 48-hour Holter monitor from baseline to 3 and 12 months; proportion of patients who were totally free of ischemia at 3 and 12 months; and percent change from baseline to 3 and 12 months in the levels of total cholesterol, LDL cholesterol, high-density lipoprotein cholesterol, triglycerides, and apolipoprotein
Drug/Procedures Used:
Patients with stable CAD and ages 65 to 85 years were randomized in a double-blind, double-dummy manner to intensive statin therapy using atorvastatin 80 mg/d (n = 446) or moderate statin therapy using pravastatin 40 mg/d (n = 445). Holter monitoring was performed at baseline, 3 months, and 12 months.
Principal Findings:
Baseline mean low-density lipoprotein (LDL) was 146 mg/dl and total cholesterol was 224 mg/dl. Average duration of ischemia on the baseline 48-hour Holter was ~119 minutes and mean number of ischemic events was 3.9. Diabetes was present in 23% of patients, and 46% had a prior myocardial infarction (MI).
While both treatment groups had a significant reduction in total duration of ischemia from baseline to 12 months (from 113.5 to 70.8 minutes for atorvastatin and from 124.3 to 78.7 minutes for pravastatin), there was no difference in the primary endpoint of change between groups (p = 0.88). Results were similar at 3 months. There was also no difference between groups in other ischemic measures, including number of ischemic episodes and ischemic burden.
Lipid reductions at 12 months were greater in the atorvastatin group compared with the pravastatin group, including LDL (55.4% for atorvastatin vs. 32.4% for pravastatin), total cholesterol (39.6% for atorvastatin vs. 21.3% for pravastatin), and triglycerides (26.3% for atorvastatin vs. 7.0% for pravastatin; all p values <0.001).
Major adverse cardiovascular events trended lower in the atorvastatin group (8.1% vs. 11.2%, p = 0.114). Mortality was significantly lower in the atorvastatin group (1.3% vs. 4.0%, p = 0.014). The occurrence of serious adverse events was similar between groups (12.1% for atorvastatin vs. 11.9% for pravastatin), but liver function test abnormalities were more frequent in the atorvastatin group (4.3% vs. 0.2%, p < 0.001).
Interpretation:
Among older patients with stable CAD, treatment with intensive statin therapy using atorvastatin 80 mg/d was not associated with a different magnitude of reduction in duration of ischemia on Holter at 12 months compared with moderate statin therapy using pravastatin 40 mg/d. Atorvastatin was associated with improvements in lipid parameters as well as a reduction in mortality.
Older CAD patients are at higher risk of myocardial ischemia, cardiac events, and mortality. Both intensive statin therapy with atorvastatin and moderate statin therapy with pravastatin were associated with reductions in myocardial ischemia at 12 months, but the degree of reduction did not differ between groups. The discrepant findings between the lack of difference in myocardial ischemia and the larger reduction in LDL with atorvastatin suggest different mechanisms identified by these measures.
Results of the present study are similar to those observed in the Vascular Basis for the Treatment of Myocardial Ischemia trial, which also showed reductions in myocardial ischemia in both the intensive (atorvastatin) and moderate (lovastatin) statin groups, without a difference between groups.
References:
Deedwania P, Stone PH, Bairey Merz CN, et al. Effects of intensive versus moderate lipid-lowering therapy on myocardial ischemia in older patients with coronary heart disease: results of the Study Assessing Goals in the Elderly (SAGE). Circulation 2007;115:700-7.
Keywords: Myocardial Infarction, Coronary Artery Disease, Lovastatin, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Heptanoic Acids, Cost of Illness, Pyrroles, Liver Function Tests, Lipoproteins, LDL, Cholesterol, Pravastatin, Electrocardiography, Ambulatory, Triglycerides, Diabetes Mellitus
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