A Phospholipase A2 Inhibitor In Development May Reduce Plaque Formation

Darapladib, a lipoprotein associated phospholipase A2 inhibitor, may help to reduce atherosclerosis. However, it does not appear to lower cholesterol levels.

Although there are cholesterol lowering drugs currently on the market that help many people prevent or slow the progression of heart disease, there are a small number of people that still experience heart attacks or strokes – despite cholesterol lowering therapy. While this has perplexed researchers for many years, a group of scientists may have found a way to help that small population of patients with a new drug in development called darapladib.

During the development of atherosclerosis, enzymes are released by white blood cells that further encourage the buildup of more fats on vessels. One of these enzymes, lipoprotein associated phospholipase A₂ (Lp-PLA₂), has been previously shown to be a marker for the presence of heart disease. Lp-PLA₂ binds to a component on LDL, or “bad” cholesterol, called apolipoprotein b and can promote the inflammation that is associated with plaque formation.

As atherosclerosis progresses, it can cause plaques to accumulate to the point that it could cause a partial blockage, either slowing blood flow and nutrients to parts of the body or breaking off and traveling to another area of the body. Darapladib appears capable of reducing plaque by blocking Lp-PLA₂.

More Studies Are Needed On Darapladib

There is only one study on darapladib to date, and the drug is currently undergoing more tests by Glaxo-Smith-Kline. The study involved 964 participants taking Lipitor (atorvastatin) that had stable coronary heart disease (CHD) or a CHD risk equivalent, such as:

• Peripheral artery disease
• Carotid stenosis greater than 50%
• Previous carotid artery surgery or stenting
• Diabetes mellitus (and taking medication for it)

Along with Lipitor, they took either a placebo or darpladib. As a result of this study, it was found that Lp-PLA₂ was reduced by as much as 66%. The investigators also found that higher doses of darapladib corresponded to a further reduction of Lp-PLA₂. Additionally, other proteins that cause inflammation, such as interleukin-6 (IL-6) and C-reactive protein (CRP), were also reduced. However, this was slight and only seen with the highest dose of darapladib. Darapladib does not appear to lower cholesterol levels.

This drug is still undergoing tests and will not be on the market for some time. While darapladib can reduce Lp-PLA₂ and other chemicals involved with inflammation that could contribute to the formation of atherosclerosis, more studies are needed in order to determine whether or not this drug can actually reduce plaque formation. If it does, darapladib may provide additional protection against atherosclerosis those individuals where statins do not seem to help.

_Source:

Mohler ER, Ballantyne CM, Davidson MH. The effect of darapladib on plasma liporprotein-associated phospholipase A2 activity and cardiovascular biomarkers in patients with stable coronary heart disease risk equivalent. J Am Coll Cardiol 2008; 51:1632-1641.