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CLINICAL STUDY: LIPID LOWERING

Intravascular ultrasound evaluation of coronary plaque regression by low density lipoprotein-apheresis in familial hypercholesterolemia

The Low Density Lipoprotein-Apheresis Coronary Morphology and Reserve Trial (LACMART)

Masunori Matsuzaki, MD, PhD, FACC^*,*, Katsuhiko Hiramori, MD, PhD, Tsutomu Imaizumi, MD, PhD, FACC, Akira Kitabatake, MD, PhD, FACC, Hitoshi Hishida, MD, PhD^¶, Masanori Nomura, MD, PhD^||, Takashi Fujii, MD, PhD^*, Ichiro Sakuma, MD, PhD, Kenichi Fukami, MD, PhD, Takashi Honda, MD, PhD^¶, Hiroshi Ogawa, MD^# and Masakazu Yamagishi, MD, PhD, FACC^**

^* Division of Cardiovascular Medicine, Department of Medical Bioregulation, Yamaguchi University School of Medicine, Yamaguchi, Japan
Second Department of Internal Medicine, Iwate Medical University School of Medicine, Iwate, Japan
Department of Internal Medicine III, Kurume University School of Medicine, Fukuoka, Japan
Department of Cardiovascular Medicine, Hokkaido University Graduate School of Medicine, Hokkaido, Japan
^|| Department of Internal Medicine, Fujita Health University School of Medicine, Nagoya, Japan
^¶ Cardiovascular Center, Saiseikai Kumamoto Hospital, Kumamoto, Japan
^# Cardiovascular Medicine, Tokuyama Chuo Hospital, Yamaguchi, Japan
^** Cardiology Division of Medicine, National Cardiovascular Center, Osaka, Japan

Manuscript received April 9, 2001; revised manuscript received April 10, 2002, accepted April 19, 2002.

^* Reprint requests and correspondence: Dr. Masunori Matsuzaki, Division of Cardiovascular Medicine, Department of Medical Bioregulation, Yamaguchi University School of Medicine, 1-1-1 Minamikogushi, Ube, Yamaguchi, 755-8505, Japan.
masunori{at}po.cc.yamaguchi.u-ac.jp

OBJECTIVES: We sought to assess the effects of low density lipoprotein (LDL)-apheresis (LDL-A) for regression of coronary plaque in familial hypercholesterolemia (FH), we set up a one-year follow-up multicenter trial using coronary angiography and intravascular ultrasound (IVUS).

BACKGROUND: It is still unclear whether aggressive lipid-lowering therapy by LDL-A leads to the regression of coronary plaque in patients with FH.

METHODS: Eighteen patients with FH were assigned to one of two groups: medication + LDL-A (LDL-A group, n = 11) and medication only (medication group, n = 7). Total cholesterol, triglycerides, high density lipoprotein cholesterol and LDL cholesterol were measured in all subjects at the outset of treatment (baseline) and every three months thereafter. Coronary angiography and IVUS were performed at the outset and after the one-year follow-up period to measure minimal lumen diameter (MLD) by coronary angiogram and plaque area (PA) by IVUS.

RESULTS: The LDL-A group showed 28.4% reduction in total cholesterol (from 275 ± 27 mg/dl to 197 ± 19 mg/dl) and 34.3% reduction in LDL cholesterol (from 213 ± 25 mg/dl to 140 ± 27 mg/dl) after one-year follow-up, while the medication group showed no changes in cholesterol levels. There were significant interactions between both treatments in total cholesterol (p = 0.0001), LDL cholesterol (p = 0.0001), MLD (p = 0.008) and PA (p = 0.017) using two-way repeated-measures analysis of variance by the SAS system (SAS Institute Inc., Cary, North Carolina). Significant differences were seen in net change in MLD (p = 0.004) and PA (p = 0.008) during the one-year follow-up period between both groups.

CONCLUSIONS: These results suggest that aggressive lipid-lowering therapy using the combination of LDL-A and lipid-lowering drugs may induce regression of coronary atherosclerotic plaque in FH patients.

Abbreviations and Acronyms   ANOVA   analysis of variance   CABG   coronary artery bypass graft surgery   CAD   coronary artery disease   CHD   coronary heart disease   FH   familial hypercholesterolemia   HDL   high density lipoprotein   HMG-CoA   hepatic hydroxymethylglutaryl-coenzyme A   ISDN   isosorbide dinitrate   IVUS   intravascular ultrasound   LDL   low density lipoprotein   LDL-A   low density lipoprotein-apheresis   MI   myocardial infarction   MLD   minimal lumen diameter   NTG   nitroglycerin   PA   plaque area   PTCA   percutaneous transluminal coronary angioplasty   QCA   quantitative coronary angiogram   TAC   time-averaged concentrations

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