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Effect of Apheresis of Low-Density Lipoprotein on Peripheral Vascular Disease in Hypercholesterolemic Patients with Coronary Artery Disease

Abraham A. Kroon, MD; Wim N.J.C. van Asten, PhD; and Anton F.H. Stalenhoef, MD
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From University Hospital Nijmegen, Nijmegen, the Netherlands. Acknowledgments: The authors thank the nursing staff of the apheresis unit, the staff of the vascular laboratory, and Ms. D. Kampschreur for assistance and Dr. E. de Groot for supervising the analysis of the videotapes at the Laboratory of the Interuniversity Cardiology Institute. Grant Support: By grant 90.065 from the Dutch Heart Foundation and by Merck, Sharp, & Dohme, Haarlem, the Netherlands. Merck, Sharp, & Dohme also provided simvastatin. Separators, adsorption columns, and other disposable materials for the apheresis unit were provided by Kaneka Deutschland, Wiesbaden, Germany. Requests for Reprints: Anton F.H. Stalenhoef, MD, Department of Internal Medicine, 541 AIG, University Hospital Nijmegen, Geert Grooteplein 8, PO Box 9101, 6500 HB Nijmegen, the Netherlands. Current Author Addresses: Dr. Kroon: Department of Internal Medicine, University Hospital Maastricht, PO Box 5800, 6202 AZ Maastricht, the Netherlands.

Copyright ©2004 by the American College of Physicians

Ann Intern Med. 1996;125(12):945-954. doi:10.7326/0003-4819-125-12-199612150-00001
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Background: Apheresis of low-density lipoprotein (LDL) is an effective lipid-lowering treatment in hypercholesterolemic patients who have coronary artery disease and are refractory to drugs. More aggressive lipid-lowering therapy may further slow the progression of atherosclerosis.

Objective: To compare the effect of LDL apheresis and simvastatin therapy with the effect of simvastatin therapy alone on the progression of peripheral vascular disease.

Design: Open, randomized, single-center study.

Setting: University hospital.

Patients: 42 men with primary hypercholesterolemia (total cholesterol level > 8.0 mmol/L) and extensive coronary atherosclerosis.

Intervention: Biweekly apheresis of LDL plus simvastatin, 40 mg/d (n = 21), or simvastatin, 40 mg/d (n = 21), for 2 years.

Measurements: Lipid and lipoprotein levels, changes in hemodynamically significant stenoses in the aortotibial tract (measured by ankle:arm systolic blood pressure ratio combined with Doppler spectrum analysis of the femoral artery), and changes in the mean intima-media thickness of three carotid artery segments.

Results: Mean baseline LDL cholesterol levels decreased from 7.8 to 3.0 mmol/L in the apheresis and simvastatin group and from 7.9 to 4.1 mmol/L in the simvastatin-only group; mean lipoprotein(a) levels decreased from 57.0 to 44.5 mg/dL (change, −19%)in the former group and increased from 38.4 to 44.5 mg/dL (change, 15%) in the latter group. In the apheresis group, the number of patients with hemodynamically significant stenoses in the aortotibial tract decreased from 9 to 7; in the simvastatin-only group, the number increased from 6 to 13 (P = 0.002). Mean intima-media thickness decreased by a mean ±SD of 0.05 ± 0.34 mm in the apheresis group and increased by 0.06 ± 0.38 mm in the simvastatin-only group (P < 0.001). According to multiple regression analysis, changes in apolipoprotein B, total cholesterol, and lipoprotein(a) levels accounted for changes in the aortotibial tract (R2 = 0.36); changes in lipoprotein(a) and apolipoprotein A1 levels accounted for changes in the intima-media thickness of the carotid artery (R2 = 0.49).

Conclusions: Aggressive lipid lowering with simvastatin and LDL apheresis decreased the intima-media thickness of the carotid artery and prevented an increase in the number of hemodynamically significant stenoses in the lower limbs. Therapy with simvastatin alone did not prevent progression of carotid or aortotibial vascular disease.


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Figure 1. The change in trend between both groups is statistically significant ( = 0.002).
The number of patients with hemodynamically significant stenoses in the aortotibial tract at baseline and at 2 years of treatment with low-density lipoprotein (LDL) apheresis plus simvastatin or simvastatin alone.P
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Figure 2.
Correlation between the change in mean intima-media thickness of the carotid artery and the change in the score of the Doppler spectrum analysis (negative values indicate worsening).
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