An Enzyme Inhibitor Might Increase Benefits of Statin Therapy

Cardiovascular disease researchers have found evidence suggesting that the cholesterol lowering benefits of statins could be increased if steps were taken to inhibit the activity of the enzyme proprotein convertase type 9 (PCSK9).

PCSK9 causes the degradation of hepatic low-density lipoprotein (LDL) receptors. Individuals who carry a mutation that stimulates the expression of PCSK9 suffer from familial hypercholesterolemia, while those with a mutation that inhibits the expression of PCSK9 have decreased LDL-cholesterol levels and cardiovascular risk. Statins, which are the drugs of choice for lowering blood cholesterol levels, have been shown to increase production of PCSK9 in cell cultures and animals models.

Investigators at Eli Lilly and Company (Indianapolis, IN, USA) studied the relation between statins and PCSK9 in human subjects. They measured circulating PCSK9 protein levels using a sandwich ELISA to quantitate serum PCSK9 levels in patients treated with atorvastatin or a placebo for 16 weeks. They reported in the February 2008 issue of the Journal of Lipid Research that atorvastatin (40 mg/day) significantly increased circulating PCSK9 levels by 34% compared with baseline and placebo and decreased LDL-C levels by 42%.

The investigators suggested that adding a PCSK9 inhibitor to statin therapy could be an approach to further decrease LDL-C levels in patients unable to reach desired results on statin therapy alone, or to effectively lower the dosage in patients who experience unwanted statin side effects.


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