Inflammation and beyond: new directions and emerging drugs for treating atherosclerosis

Expert Opin Emerg Drugs. 2017 Mar;22(1):1-26. doi: 10.1080/14728214.2017.1269743. Epub 2016 Dec 22.

Abstract

Cardiovascular (CV) atherosclerotic disease remains the leading cause of morbidity and mortality worldwide, despite the advances in contemporary therapies. Inflammation is an important process in atherosclerosis, leading to plaque rupture and acute coronary syndrome. Although statin therapy has substantially reduced CV events in primary and secondary prevention, many treated patients will have recurrent adverse CV events despite the standard of care. Thus, drug development aiming to target inflammatory pathways seems a promising avenue for novel therapies in atherosclerosis. Areas covered: Statins have been extensively studied and are the most effective lipid-lowering drugs available for CV prevention. Novel anti-inflammatory drugs are being tested in Phase II and III trials, targeting pathways like interleukin-1, leukotrienes, TNF-α, P-selectin, CCL2-CCR2 and MAP Kinase. Expert opinion: Novel anti-inflammatory therapies seem promising additions to address the residual CV risk present despite the current standard of care, but large clinical trials have not yet shown beneficial effects on clinical events. PCSK9 inhibitors have been shown to substantially reduce LDL-C, however their long-term safety and effects on CV risk are currently being investigated. Pharmacogenomics holds great potential in future lipid trials, enabling the identification of patients who will respond with greater benefits and smaller risk to therapies and to decrease failure rates in drug development, as genotype-dependent effects of the CETP inhibitor dalcetrapib were shown in the dal-OUTCOMES and dal-PLAQUE-2 trials.

Keywords: Atherosclerosis; C-reactive protein; P-selectin; cardiovascular disease; inflammation; interleukin-1; leukotrienes; p38 MAP kinase; serpin; statins; tumor necrosis factor alpha.

Publication types

  • Review

MeSH terms

  • Acute Coronary Syndrome / drug therapy
  • Acute Coronary Syndrome / pathology
  • Animals
  • Anti-Inflammatory Agents / adverse effects
  • Anti-Inflammatory Agents / pharmacology
  • Anti-Inflammatory Agents / therapeutic use*
  • Atherosclerosis / drug therapy*
  • Atherosclerosis / pathology
  • Cardiovascular Diseases / etiology
  • Cardiovascular Diseases / prevention & control
  • Drug Design
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / therapeutic use
  • Hypolipidemic Agents / therapeutic use
  • Inflammation / drug therapy*
  • Inflammation / pathology
  • Pharmacogenetics
  • Risk Factors

Substances

  • Anti-Inflammatory Agents
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Hypolipidemic Agents