In a new study, researchers have found that darapladib, a novel inflammation inhibitor, shows no primary endpoint advantage over placebo in patients with chronic coronary heart disease with a high level of background care. The data was released March 30 as part of ACC.14 in Washington, DC, and simultaneously published in the New England Journal of Medicine.

The drug is designed to inhibit Lp-PLA2, a biomarker of inflammation in blood vessels that is generally found on LDL cholesterol. Since high Lp-PLA2 levels are an associated risk factor for coronary heart disease, and linked with vulnerable plaque, an unstable waxy buildup in arterial walls that is associated with heart attacks and strokes, the hope was that darapladib would reduce the likelihood of such plaque resulting in an artery-blocking clot.

In an international, phase III double-blind trial, 15,828 patients with chronic coronary heart disease (median age 65-years-old) were randomly assigned to receive a daily 160-mg darapladib tablet or placebo. With a median follow-up of 3.7 years darapladib showed no significant benefit with 769 event (9.7 percent) compared with 819 events (10.4) for the placebo. Despite not achieving its primary endpoint, a secondary endpoint showed a nominally significant reduction in major coronary events such as heart attack, an urgent need for angioplasty or bypass surgery, or death. Those that took darapladib had a 10 percent relative risk reduction, with 737 events (9.3 percent) in major coronary events compared with 814 events (10.3 percent) in the placebo group.

"These events are clinically important, with substantial consequences for patients," says Harvey D. White, MD, director of Coronary Care Unit, Green Lane Cardiovascular Unit, Auckland City Hospital, New Zealand, and a co-chair of the study. "The effects on these endpoints could support the hypothesis that inhibition of Lp-PLA2 with darapladib may alter the composition of atherosclerotic plaques to a less vulnerable state and reduce ischemic events related to coronary artery plaque progression and rupture."

Warranting further analysis of biomarkers, Lp-PLA2 levels, and genetic sub-studies, insight into darapladib's potential effects on the prevention of coronary events in patients with stable coronary heart disease will soon be underway. White notes, "As with statins it may take some time for the anti-inflammatory effect of darapladib to alter the composition of coronary artery plaque, resulting in less vulnerability and fewer coronary events."

Keywords: Stroke, Plaque, Atherosclerotic, Follow-Up Studies, Cholesterol, LDL, Coronary Care Units, Coronary Disease, Risk Factors, Angioplasty, Benzaldehydes, Oximes, Biomarkers, Hospitals, Urban, Coronary Vessels, 1-Alkyl-2-acetylglycerophosphocholine Esterase