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LDL-Apheresis Atherosclerosis Regression Study (LAARS). Effect of aggressive versus conventional lipid lowering
A A Kroon1, W R Aengevaeren, T van der Werf
1Department of Internal Medicine, University Hospital Nijmegen, Nijmegen, The Netherlands.
Insights
Intensive lipid lowering with LDL-apheresis significantly improved exercise tolerance in men with coronary artery disease. While not altering lesion size, this aggressive approach offered functional benefits that may precede visible changes.
Area of Science:
- Cardiology
- Vascular Biology
- Lipid Metabolism
Background:
- Coronary atherosclerosis progression can be slowed by intensive lipid lowering.
- Low-density lipoprotein (LDL) apheresis can achieve very low LDL cholesterol levels.
- Severe coronary atherosclerosis in hypercholesterolemic men warrants investigation into aggressive lipid-lowering strategies.
Purpose of the Study:
- To evaluate the impact of LDL apheresis combined with medication on coronary atherosclerosis progression.
- To compare the effects of intensive lipid lowering versus standard medication on coronary artery disease (CAD) in men.
Main Methods:
- A randomized study involving 42 men with hypercholesterolemia and severe coronary atherosclerosis.
- Participants received either biweekly LDL apheresis plus simvastatin (40 mg/day) or simvastatin alone for 2 years.
- Coronary angiography and bicycle exercise tests were used to assess disease progression and functional capacity.
Main Results:
- LDL apheresis achieved a 63% reduction in LDL cholesterol, compared to 47% with medication alone.
- No significant differences in average mean segment diameter or minimal obstruction diameter were observed between groups.
- The LDL apheresis group showed a tendency for decreased stenosis and significant improvements in exercise test parameters, including increased time to ST-segment depression.
Conclusions:
- Both LDL apheresis with medication and medication alone halted angiographic progression of coronary artery disease over 2 years.
- Intensive lipid lowering via LDL apheresis induced functional improvements in patients, potentially indicating benefits that precede anatomical changes.
Background:
Intensive lipid lowering may retard the progression of coronary atherosclerosis. LDL-apheresis has the potential to decrease LDL cholesterol to very low levels. To assess the effect of more aggressive lipid lowering with LDL-apheresis, we set up a randomized study in men with hypercholesterolemia and severe coronary atherosclerosis.
Methods And Results:
For 2 years, 42 men were treated with either biweekly LDL-apheresis plus medication or medication alone. In both groups a dose of simvistatin of 40 mg per day was administered. Baseline (mean+/-SD) LDL cholesterol was 7.8+/-1.9 mmol x L(-1) and 7.9+/-2.3 mmol x L(-1) in the apheresis and medication groups, respectively. The mean reduction in LDL cholesterol was 63% (to 3.0 mmol x L(-1)) and 47% (to 4.1 mmol x L(-1)), respectively. Primary quantitative coronary angiographic end points were changes in average mean segment diameter and minimal obstruction diameter. No differences between the apheresis and medication groups were found in mean segment diameter (-0.01+/-0.16 mm versus 0.03+/-0.16 mm, respectively) or in minimal obstruction diameter (0.01+/-0.13 mm versus 0.01+/-0.11 mm, respectively), expressed as means per patient. On the basis of coronary segment, mean percent stenosis of all lesions showed a tendency to decrease; only in the apheresis group more minor lesions disappeared in comparison to the medication group. On bicycle exercise tests, the time to 0.1 mV ST-segment depression increased significantly by 39% and the maximum level of ST depression decreased significantly by 0.07 mV in the apheresis group versus no changes in the medication group.
Conclusions:
Two years of lipid lowering both with medication alone or LDL-apheresis with medication showed angiographic arrest of the progression of coronary artery disease. However, more aggressive treatment induced functional improvement, which may precede anatomic changes.