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Long-Term Effect of Low-Density Lipoprotein Apheresis on Plasma Lipoproteins
and Coronary Heart Disease in Native Vessels and Coronary Bypass in Severe Heterozygous
Familial Hypercholesterolemia
Metabolism
1998;47:863-868.
Werner O. Richter, Markus G. Donner, Berthold Höfling, Peter Schwandt
Individuals with familial hypercholesterolemia (FH) are at high risk for severe
atherosclerosis, with coronary lesions presenting at an early age. While a portion
of individuals with FH respond to intensive lipid-lowering treatment using medications,
some do not; as a result, these individuals are at high risk for the rapid progression
of coronary lesions. These patients who do not respond to lipid-lowering medications
are candidates for LDL-apheresis treatment.
The main goal of this study was to evaluate whether the positive short-term effects
of LDL-apheresis could be preserved over the long-term. To examine this, 34 patients
(21 men and 13 women) with heterozygous FH and angiographically-proven coronary
artery disease who did not respond to lipid-lowering drugs were placed on LDL-apheresis
for as many as 8 years. The mean treatment period was 4.6 ± 2.6 years (range
8.6–0.9). Apheresis techniques included immunoadsorption (IA; n=18), dextran
sulfate adsorption (DS; n=8) or the heparin-induced method (HI; n=8). All lipid-lowering
drugs were removed at the initiation of treatment. Subsequently, simvastatin at
the maximal dose was added after 6 months to 3 years. Clinical course, lipoprotein
concentrations, results of coronary angiograms, and side effects in patients undergoing
LDL-apheresis were reported.
Regardless of apheresis technique, LDL-C declined 62.6%, from 4.8 ± 1.0 mmol/L
(mean ± SD) pretreatment to 1.8 ± 0.4 mmol/L posttreatment, and Lp(a)
levels decreased 48.5% from 33 ± 50 mg/dL to 17 ± 19 mg/dL. Regression
of coronary artery disease (CAD), as defined by definite regression of coronary
lesions, was observed in 4 (11.8%) patients, whereas 19 patients demonstrated a
cessation of progression of the lesions. At the completion of the study, all patients
who underwent LDL-apheresis and had not undergone any other coronary revascularization
procedure were asked to complete a score on the severity and frequency of angina
pectoris at baseline and at study completion. Of the 23 patients eligible for scoring
of anginal symptoms, 5 reported decreased frequency and severity of angina pectoris.
Throughout the entire period, 3 sudden deaths, 1 nonfatal myocardial infarction,
and 5 hospital admissions as a result of unstable angina pectoris were observed.
The results of this study show that for those patients with FH who do not readily
respond to drug treatment, aggressive reductions in LDL-C with a combination of
LDL-apheresis and lipid-lowering drug treatment can prevent progression of CAD in
the majority of cases and lead to measurable clinical improvement. This stabilization
can be maintained for periods up to 8.6 years.
Click for full abstract.
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