To test the hypothesis that aggressive cholesterol lowering results in a rapid regression of coronary atherosclerosis, the effect of low-density lipoprotein (LDL)-apheresis for 1 year on coronary artery diameters was studied in patients with heterozygous familial hypercholesterolemia. LDL-apheresis was performed every 2 weeks in 13 patients with LDL-cholesterol levels > or = 200 mg/dL despite treatment with conventional dietary and drug therapies. Coronary arteriography was performed before and 1 year after the initiation of treatment. The LDL-cholesterol level was decreased by an average of 71% immediately after the initial LDL-apheresis and by 30% before the second apheresis. Such phasic changes were observed throughout the trial. Computer-assisted automated quantitative arteriograms analyzed 101 proximal coronary segments. The mean lumen diameter of angiographically normal sections of each segment was slightly but significantly increased from 2.93 +/- 0.89 mm at baseline to 3.05 +/- 0.93 mm at the follow-up arteriogram (P < 0.05); 54 of the 101 segments showed a lesion stenosed by 20% or more in diameter. The minimal diameter of individual lesions was also significantly increased from 2.17 +/- 0.67 mm to 2.36 +/- 0.76 mm (P < 0.05), and thus the diameter stenosis was significantly reduced from 32.3 +/- 10.5% to 28.2 +/- 12.1% (P < 0.05). It is concluded that 1 year of aggressive cholesterol lowering, using LDL-apheresis, can significantly reduce coronary atherosclerosis in patients with familial hypercholesterolemia.