Low Density Lipoprotein Apheresis Improves Regional Myocardial Perfusion in Patients With Hypercholesterolemia and Extensive Coronary Artery Disease: The LDL-Apheresis Atherosclerosis Regression Study (LAARS)

Objectives. In a randomized study we evaluated the effect of biweekly low density lipoprotein (LDL) apheresis plus simvastatin versus medication alone on regional myocardial perfusion.

Background. In patients with severe hypercholesterolemia, diet and lipid-lowering drugs are often insufficient to achieve optimal LDL cholesterol values. Low density lipoprotein apheresis is a very effective lipid-lowering therapy. Assessment of regional myocardial perfusion enables evaluation of the functional state of the coronary circulation.

Methods. We studied 42 patients with severe hypercholesterolemia and extensive coronary artery disease who were randomized to diet and simvastatin with or without biweekly LDL apheresis. Regional myocardial perfusion was assessed by digital subtraction angiography with videodensitometric calculation of hyperemic mean transit time (HMTT) of contrast medium at baseline and after 2 years of therapy.

Results. Low density lipoprotein cholesterol decreased by 63% (to 3.0 mmol/liter) in the LDL apheresis group and by 47% (to 4.1 mmol/liter) in the medication group. Paired HMTT measurements were assessed in 43 regions in the LDL apheresis group and 35 regions in the medication group. In the LDL apheresis group, regional HMTT decreased over 2 years from 3.35 ± 1.18 (mean ± SD) to 2.87 ± 0.82 s (−14%, p = 0.001), whereas no change in the medication group was observed: 2.95 ± 1.06 to 2.96 ± 0.90 s (p = NS). In the patient-based comparison, the mean change in HMTT was −0.45 s (−14%, p = 0.01) in the LDL apheresis group and −0.05 s (−2%, p = NS) in the medication group, respectively. Only exercise-induced ischemia improved in the LDL apheresis group.

Conclusions. Biweekly LDL apheresis plus simvastatin decreased time-averaged LDL cholesterol levels by an additional 31% (1.1 mmol/liter) compared with medication alone. After 2 years of therapy, regional myocardial perfusion improved in the LDL apheresis group and remained unchanged in the medication group. Thus, aggressive reduction of LDL cholesterol has a favorable effect on regional myocardial perfusion and alleviates ischemia.

(J Am Coll Cardiol 1996;28:1696–704)>