Low-Density Lipoprotein (LDL) Apheresis Using H.E.L.P. Therapy
Low-Density Lipoprotein (LDL) Apheresis Using H.E.L.P. Therapy
The objectives of this post-surveillance study are to continue to evaluate the safety and
 effectiveness of the H.E.L.P. System. The safety and effectiveness will be assessed by
 evaluating the occurrence of death, cardiovascular events or interventions, angina, and
 serious unanticipated adverse effects. Laboratory assessments will be made to document
 low-density lipoprotein cholesterol (LDL-C) reduction and any effects on other blood
 components. Quality of life assessments will also be made.

 The study will also assess the modifications to the H.E.L.P. System, including:

 -  use of a single heparin adsorber, instead of two smaller adsorbers;

 -  change in the supplier of the ultrafilter (from Secon to Toray);

 -  reduction in the number of blood lines from eleven to nine;

 -  change from a single-layer to a two-layer precipitate filter.

 The safety and efficacy of the device specific to these modifications will be evaluated by
 comparing the safety and efficacy data from the patient registry to the data from the initial
 clinical study on the device as originally designed.
H.E.L.P. therapy is indicated for use in treating patients with familial hypercholesterolemia
 (FH) who have undergone six months of optimal diet and drug therapy and whose LDL-C level
 remains > 300 mg/dl in the absence of CHD or > 200 mg/dl with documented CHD. These patients
 are divided into three subgroups of interest:

 -  Group A: functional hypercholesterolemic homozygotes with LDL-C > 500mg/dl;

 -  Group B: functional hypercholesterolemic heterozygotes with LDL-C > 300mg/dl;

 -  Group C: functional hypercholesterolemic heterozygotes with LDL-C > 200mg/dl and
 documented CHD.

 Optimal diet therapy is defined as having received instruction by a trained dietitian in the
 use of a diet meeting the National Cholesterol Education Program (NCEP) Step 2 criteria (<
 30% of calories as fat, < 7% of calories as saturated fat, and < 200 mg of dietary
 cholesterol per day). Optimal drug therapy is defined as having been tried on at least two
 separate classes of effective serum LDL-C lowering agents (>15% reduction) as currently
 available for at least six months. These drugs include hydroxy methyl glutaryl (HMG) CoA
 reductase inhibitors, fibric acid derivatives, niacin, and anion exchange resins. These
 agents should be used in combination at maximal doses as tolerated by the patient under the
 supervision of their treating physician to monitor side effects.

 Documented coronary heart disease (CHD) includes documentation of coronary heart disease by
 coronary angiography or a history of myocardial infarction (MI), coronary artery bypass
 surgery (CABG), percutaneous transluminal coronary angioplasty (PTCA) or alternative
 revascularization procedure (e.g., atherectomy or stent), or progressive angina documented by
 exercise or non-exercise stress test.

 The primary criteria for evaluating the safety and effectiveness of the device will be:

 -  Occurrence of Death

 -  cardiovascular deaths

 -  non-cardiovascular deaths

 -  Occurrence of Cardiovascular Events

 -  MI - stroke

 -  unstable angina - transient ischemic attack (TIA)

 -  congestive heart failure - pulmonary embolism

 -  arrhythmia - peripheral vascular disease

 -  hypertension

 -  Occurrence of Surgical or Non-Surgical Intervention Procedure of the Treatment of
 Atherosclerotic Cardiovascular Disease (ASCVD) including:

 -  coronary artery bypass graft (CABG) surgery

 -  peripheral vascular bypass surgery

 -  percutaneous transluminal coronary angioplasty (PTCA)

 -  percutaneous transluminal coronary artery bypass graft angioplasty

 -  percutaneous transluminal peripheral angioplasty (PTA)

 -  coronary atherectomy (device)

 -  coronary artery bypass graft atherectomy (device)

 -  peripheral atherectomy (device)

 -  carotid endarterectomy (non-device)

 -  peripheral endarterectomy (non-device)

 -  coronary artery laser surgery

 -  coronary artery bypass graft laser surgery

 -  peripheral vascular laser surgery

 -  coronary artery stent placement

 -  coronary artery bypass graft stent placement

 -  peripheral vascular stent placement

 -  repair of atherosclerotic aortic and arterial aneurysms

 -  limb amputation for ASCVD

 -  Frequency and severity of CHD Symptoms:

 -  chest pain (angina),

 -  shortness of breath

 -  claudication

 -  Use of CHD Medications for treatment of:

 -  angina

 -  heart failure

 -  arrhythmias

 -  hypertension

 -  hyperlipidemia

 -  Use of Lipid-Lowering Medications and Other Cardiovascular Medications Concomitantly

 -  Laboratory Assessments (lipid, lipoprotein, chemistry, and clotting factors)

 -  Quality of life assessments (SF-36)

 -  Occurrence of Serious and/or Unanticipated Adverse Events Reported During Treatment
 (e.g., hypotension, nausea, vomiting, syncope)

 -  Occurrence of other serious illnesses

 -  Acute Reduction of LDL-C
Inclusion Criteria:

 -  Adequate venous access

 -  Laboratory values:

 -  Hematocrit 30% or greater

 -  platelet count between 100,000 and 1,000,000/ml

 -  Premenopausal women must be surgically sterilized or be on oral contraceptive therapy
 and have a negative pregnancy test at the onset of treatment with H.E.L.P.

 -  Patients have familial hypercholesterolemia and have undergone at least 6 months
 optimal diet and drug therapy and fit group A, B, or C

 Exclusion Criteria:

 -  Presence of any of the following conditions:

 -  untreated hypothyroidism

 -  decompensated congestive heart failure

 -  major arrhythmia

 -  uncontrolled diabetes mellitus

 -  any malignancy

 -  disorders associated with excessive bleeding (e.g., peptic ulcer and hemophilia)

 -  established or suspected intracranial disease which might cause intracranial
 bleeding if the patient is anticoagulated

 -  any other medical disorders which lead the treating physician to believe that
 H.E.L.P. treatment would not be in the best interest of the patient

 -  current treatment with anticoagulants

 -  diastolic BP > 100 mmHg recorded in two occasions at least 24 hours apart.

 -  patients under 18 years of age

 -  positive test for Hepatitis [Type A (IgM) or B] antigen, Hepatitis C antibody, or
 HIV (or diagnosis of AIDS)