Reconstituted HDL: A Therapy for Atherosclerosis and Beyond

Andrew J Murphy; Jaye Chin-Dusting; Dmitri Sviridov

Disclosures

Clin Lipidology. 2009;4(6):731-739. 

In This Article

Advantages & Disadvantages of rHDL Therapy

Studies examining the antiatherogenic potential of rHDL therapy in humans have demonstrated multiple advantages with this approach in treating cardiovascular and related diseases. Administration of rHDL has been shown to stabilize the phenotype of the atherosclerotic plaque in patients with PVD. It would be of great interest to examine the effects in other vessels and while there is some evidence to suggest that rHDL remodels coronary plaques using IVUS, it remains undetermined as to what extent rHDL changes coronary plaque composition. The evidence that HDL can regulate insulin secretion and glucose uptake after a single high-dose infusion in Type 2 diabetics opens up a new avenue for rHDL therapy. Thus, results from future studies on the long-term effects of increasing HDL levels in Type 2 diabetics is greatly anticipated.

To date, rHDL has only been examined in small cohorts with acute applications where it has overall been shown to be effective. However, there remains a lack of evidence to prove that rHDL therapy has a clear beneficial effect on cardiovascular outcomes. Clearly, there is a need for such studies to be validated in larger multicenter trials. The major disadvantage with rHDL therapy is the cost and practical issues associated with producing large amounts of rHDL along with the costs and time associated with an infusion drug compared with an oral drug. This may complicate its use as a chronically administered drug and limits its application. Repeated infusions in humans were not met with any increase in adverse events compared with the placebo group. In addition, the rHDL appears to be well tolerated and does not appear to cause an immune response. In addition, as apoA-I is purified from human plasma, the blood undergoes all the same screening methods as it would if used in the clinic for transfusions.[29] However, in stating this, no long-term studies have been carried out that allow for the observation of an immune response to rHDL particles.

If rHDL therapy can indeed lead to plaque regression, it would need to be determined if this treatment would be preferable over surgery. The obvious advantage of rHDL therapy over HDL pathway inhibitors (such as cholesteryl ester transfer protein) is that it is a direct avenue to increase HDL levels with a known population of HDL. What does appear to be evident is that acute administration of rHDL could have great potential in the clinic for rapidly stabilizing plaques and could be used in either pre- or post-operative care to minimize the risk of plaque rupture resulting in myocardial infarction or stroke.

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