Emerging anti-inflammatory drugs for atherosclerosis

Abstract

Introduction: Cardiovascular disease is the most common cause of morbidity and mortality worldwide. Inflammation is responsible for initiation and progression of atherosclerosis, and leads to plaque vulnerability. Evidence-based therapies reduce the risk of initial and recurrent cardiovascular events but many patients experience recurrent events due to the failure of conventional therapies to adequately address inflammation.

Areas covered: Statins were originally developed for their LDL cholesterol-lowering effects, but are now thought to improve cardiovascular morbidity and mortality through anti-inflammatory effects as well. Drugs that inhibit the various inflammatory pathways responsible for atherosclerosis are the subject of current research. These include antioxidants, phospholipase A₂ inhibitors, leukotriene pathway inhibitors, CCL2-CCR2 pathway inhibitors, non-specific anti-inflammatory drugs (i.e., methotrexate), IL-1 inhibitors and p-selectin inhibitors.

Expert opinion: Currently, only three anti-inflammatory drugs (methotrexate, darapladib and canakinumab) are being investigated in Phase III clinical trials of atherosclerosis. The development of cardiovascular drugs requires long, expensive Phase III trials to demonstrate incremental improvement in cardiovascular events. Imaging end points and soluble biomarkers accelerate Phase II development, but further validation is needed before these can be used as surrogate end points in the large trials leading to drug approval. Improved access to currently available therapies like statins would decrease the burden of cardiovascular disease worldwide.

Keywords::

• anti-inflammatory agents
• atherosclerosis
• canakinumab
• darapladib
• statin