Drug Reduces Biomarkers in Coronary Heart Disease

Darapladib reduces lipoprotein-associated phospholipase A2 (Lp-PLA2) activity and other inflammatory markers in patients with coronary heart disease who are receiving statins, according to a study in the April 29 issue of the Journal of the American College of Cardiology. A related study found that statins have variable effects on oxidative stress markers in patients with high cholesterol.

In the first study, Emile R. Mohler III, M.D., of the University of Pennsylvania in Philadelphia and colleagues randomly assigned 959 patients with coronary heart disease or its risk equivalent who were receiving atorvastatin to one of three doses of darapladib or placebo. They found that darapladib inhibited Lp-PLA2 in a dose-dependent manner, with reductions in interleukin-6 and high-sensitivity C-reactive protein at the highest dose.

In the second study, Bonnie Ky, M.D., from the University of Pennsylvania and colleagues randomly assigned 120 patients with hypercholesterolemia to 40 milligrams pravastatin, 10 milligrams or 80 milligrams atorvastatin, or placebo.

The researchers found that pravastatin led to a significant reduction in Lp-PLA2, while 10 milligrams atorvastatin led to a significant reduction in oxidized low-density lipoprotein. There were significant increases in oxidized phospholipids/apolipoprotein B-100 particle with pravastatin and 80 milligrams atorvastatin.

"Because inflammation plays a pivotal role in atherothrombosis and its clinical complications, inhibition of Lp-PLA2 might have promise as a suitable strategy to combat residual cardiovascular risk," Wolfgang Koenig, M.D., of the University of Ulm Medical Center in Germany writes in an editorial.

The first study received support from GlaxoSmithKline. The second received a grant from Bristol-Myers Squibb. The author of the editorial has a relationship with GlaxoSmithKline.

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