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Effect of HELP-LDL-Apheresis on Outcomes in Patients With Advanced Coronary Atherosclerosis and Severe Hypercholesterolemia

Atheroslerosis
1998;139:401-409.

Jai-Wun Park, Mechthild Merz, Peter Braun.

The authors undertook a prospective, open, single center study in patients with advanced coronary atherosclerosis who were resistant to treatment with lipid-lowering drugs and/or suffered from elevated fibrinogen or Lp(a) levels. Their aim was to assess the impact of aggressive lowering of LDL-C, fibrinogen, and Lp(a) with diet, medication, and weekly heparin-induced apheresis therapy on clinical outcomes (death, angina pectoris, exercise tolerance, and coronary status after 10 months of the heparin-induced therapy; LDL-C, fibrinogen, and Lp(a) levels after long-term treatment with the heparin-induced method).

The study consisted of 44 patients with advanced coronary artery disease (CAD) and LDL-C exceeding 160 mg/dL despite therapy with diet and lipid-lowering medications. In contrast to previous trials, this study included patients with left ventricular ejection fraction <0.35 treated with ACE inhibitors. Improvement of clinical status via the heparin-induced method was defined as an increase of exercise tolerance, decrease of antianginal drug use, and/or decrease of angina pectoris severity and frequency. Blood chemistries included measurement of total cholesterol, triglycerides, HDL-C, LDL-C, Lp(a), and fibrinogen. Bicycle ergometry in the sitting position was used as an exercise test. Coronary angiography was performed to monitor CAD status.

LDL-apheresis (mean of 15.5 ± 9.5 months) resulted in mean per-treatment percent reduction of total cholesterol (44.8 ± 8.7), LDL-C (55.5 ± 8.6), Lp(a) (60.8 ± 10.2), and fibrinogen (53.8 ± 6.5).
Improvement in clinical status was found in 73% of patients, with 11% showing no change and 16% demonstrating deterioration in clinical status.
Twenty-three (52%) patients reported less frequency and severity of angina pectoris, with 17 patients (39%) reporting no change and four patients (9%) reporting an increase.
Maximal workload as observed by bicycle ergometry testing increased significantly from 101 ± 41 watts (W) to 119 ± 46 W (P<0.001) posttreatment.
Ten (40%) patients who underwent coronary angiography demonstrated CAD progression, whereas two (8%) patients had CAD regression. Nonetheless, eight out of the 10 (80%) progressors demonstrated clinical improvement. This apparent contradiction between CAD progression and clinical improvement was believed to be due to the impact of heparin-induced therapy on rheologic and antithrombotic mechanisms.

The authors concluded that apheresis via the heparin-induced method can safely and effectively lower LDL-C, Lp(a), and fibrinogen in patients with advanced coronary atherosclerosis and severe hypercholesterolemia. Frequent treatments with the heparin-induced method resulted in clinical improvement even in patients with angiographically-demonstrable CAD progression.

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