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Relationship between plasma LDL concentrations during treatment with pravastatin and recurrent coronary events in the
F M Sacks1, L A Moyé, B R Davis
1Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Mass, USA. fsacks@hsph.harvard.edu
Insights
Lowering LDL cholesterol reduced coronary events in patients with heart disease, but only down to approximately 125 mg/dL. Further reductions in LDL cholesterol did not provide additional cardiovascular benefits.
Area of Science:
- Cardiology
- Clinical Lipidology
- Preventive Cardiology
Background:
- Low-density lipoprotein (LDL) cholesterol lowering effectively reduces recurrent coronary events in patients with established coronary heart disease.
- However, the precise extent of LDL cholesterol reduction needed for optimal risk reduction remains incompletely understood.
Purpose of the Study:
- To investigate the relationship between achieved LDL cholesterol levels and the rate of recurrent coronary events in patients post-myocardial infarction.
- To determine if the degree of LDL cholesterol reduction, rather than the absolute achieved level, predicts cardiovascular outcomes.
Main Methods:
- The Cholesterol and Recurrent Events (CARE) trial randomized patients with prior myocardial infarction to pravastatin or placebo.
- Baseline and follow-up lipid levels, including LDL cholesterol, were assessed. The primary endpoint was coronary death or recurrent myocardial infarction.
Main Results:
- Pravastatin significantly reduced the risk of coronary death or recurrent myocardial infarction by 24%.
- Achieved LDL cholesterol levels during follow-up were a significant predictor of event rates, but the extent of LDL reduction was not.
- Coronary event rates decreased as LDL cholesterol fell to approximately 125 mg/dL, with no further significant benefit observed below this level.
Conclusions:
- Achieved LDL cholesterol concentrations around 125 mg/dL were associated with reduced coronary events in patients treated with pravastatin or placebo.
- LDL cholesterol levels below 125 mg/dL did not confer additional cardiovascular benefits in this patient cohort.
- The absolute or percentage reduction in LDL cholesterol showed a weak relationship to the observed reduction in coronary events.
Background:
Although LDL lowering has been shown to reduce recurrent coronary events in patients with coronary heart disease, little direct information is available on the extent of LDL lowering required to achieve this outcome.
Methods And Results:
The Cholesterol and Recurrent Events (CARE) trial compared pravastatin and placebo in patients who had experienced myocardial infarction (MI) who had average concentrations of total cholesterol <240 mg/dL (baseline mean, 209 mg/dL) and LDL cholesterol (LDL) 115 to 174 mg/dL (mean, 139 mg/dL). Pravastatin reduced coronary death or recurrent MI by 24%. In multivariate analysis, the LDL concentration achieved during follow-up was a significant, although nonlinear, predictor of the coronary event rate (P=.007), whereas the extent of LDL reduction was not significant, whether expressed as an absolute amount (P=.97) or a percentage (P=.76). The coronary event rate declined as LDL decreased during follow-up from 174 to approximately 125 mg/dL, but no further decline was seen in the LDL range from 125 to 71 mg/dL. In multivariate analysis, triglyceride but not HDL concentrations during follow-up were weakly but significantly associated with the coronary event rate.
Conclusions:
The LDL concentrations achieved during treatment with pravastatin or placebo were associated with reduction in coronary events down to an LDL concentration of approximately 125 mg/dL. LDL concentrations <125 mg/dL during treatment were not associated with further benefit. Absolute or percentage reduction in LDL had little relationship to coronary events.
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