Targeting Inflammation In Atherosclerosis After Darapladib: Does The IL-6 Pathway Hold The Answer?

Targeting inflammation appears to be a promising complementary approach to lipid-lowering drugs in atherosclerosis, but the question of which pathway in a complex system to target remains open. The failure of GlaxoSmithKline’s darapladib in the STABILITY trial may have dealt a fatal blow to phospholipase A2 enzymes as targets, but the interleukin-6 pathway is gaining attention with the ongoing CANTOS study of Novartis’ canakinumab and the NHLBI’s CIRT study of low-dose methotrexate.

As scientific awareness of the importance of inflammation in atherosclerosis has grown, the development of anti-inflammatory drugs to reduce cardiovascular risk has stumbled. But even in the shadow of the failure of GlaxoSmithKline PLC’s phospholipase A2 inhibitor darapladib in the STABILITY trial, the recent American College of Cardiology annual meeting showcased the continuing interest in anti-inflammatory approaches to atherosclerosis treatment.

Some researchers touted the potential of a different pathway centered on interleukin-6 signaling, while others questioned the ability of drugs...