LDL apheresis for severe refractory hypercholesterolemia

Familial hypercholesterolemia is an autosomal dominant disorder resulting in severe elevation of total and LDL cholesterol due to defective hepatic LDL receptor. Heterozygotes occur in about 1 of 500 people in the United States. In some populations, such as French Canadians, the incidence for heterozygotes may be increased. Many people with familial hypercholesterolemia experience recurrent cardiovascular events at a young age and eventually die, prematurely.

For many, aggressive combination pharmacotherapy is sufficient and effective. However, in those in whom medications are either ineffective or not tolerated, LDL apheresis is another option. LDL apheresis is FDA-approved for the management of patients with severe elevation of LDL cholesterol who have not responded to at least six months of dietary modification and maximum tolerated drug therapy consisting of a trial of at least two classes of lipid -lowering medications.

There are two groups of patients for which LDL apheresis is indicated:

Patients with an LDL level >300 mg/dL.
Patients with an LDL level between 200 mg/dL to 300 mg/dL with CV disease.

During LDL apheresis, the plasma is separated from whole blood, and LDL and other apolipoprotein B-containing particles are removed from the plasma. Then, the plasma and blood are recombined and returned back to the patient. The entire procedure takes approximately two to three hours to perform.

A single LDL apheresis treatment may lower LDL between 73% and 83%. Because patients have a genetic defect, however, treatment must be repeated indefinitely. In general, individuals with LDL levels starting at>300 mg/dL are treated once per week, while individuals with LDL levels starting at 200 mg/dL are usually treated once every two weeks. Patients should continue their diet and lipid-lowering medications after initiating LDL apheresis.

LDL apheresis has been shown to regress atherosclerotic plaque and decrease the frequency CV events. In one study, the rate for CV events, death and subsequent interventions were reduced by 72% after six years of LDL apheresis compared to management with medication alone. Besides lowering LDL, LDL apheresis also lowers triglycerides, very-low density lipoprotein (VLDL), apolipoprotein B, fibrinogen, lipoprotein A, C-reactive protein, lipoprotein-associated phospholipase A2, blood viscosity and other markers associated with increased CVD risk.

Adverse events are rare. Transient hypotension during the procedure is the most common adverse event. In clinical trials, hypotension occurred in <1% of all treatments. ACE inhibitors increase this risk, presumably mediated through bradykinins. Therefore, we switch all patients on angiotensin-converting enzyme inhibitors to angiotensin receptor blockers which do not have this effect. Other antihypertensive agents should be withheld for 24 hours before the procedure. Our own patients undergoing LDL apheresis have tolerated the procedure well without any ill effects.

One disadvantage, besides the requirement of two or three-hour treatments every two weeks, is that LDL apheresis is expensive. Severe hypercholesterolemia thathas failed to respond to usual therapy, however, can also be expensive when considering not only the literal expense of repeated procedures and revascularization, but also the personal cost in terms of recurrent events and premature death. For patients in whom it is indicated, LDL apheresis is medically necessary and covered by many insurance plans.

Unfortunately, there continues to be a misconception that familial hypercholesterolemia is rare and that LDL apheresis is available only at large academic medical centers. Because of this, many patients who could potentially benefit from such life-saving therapy are never offered the opportunity.

Mabuchi H. Am J Cardiol.1998;82:1489-1495.

Mehta PK. Current Treatment Options in Cardiovascular Medicine. 2009;11:279-288.