Novel Therapies for Plaque Inflammation

12th Biennial Meeting of the International Andreas Gruentzig Society:  Rio de Janeiro - February 2-6, 2014

Novel Therapies for Plaque Inflammation:

  • Inflammation is the key component of vulnerable plaque. Recently, therapies exist in animal models but have been disappointing in human trials.
  • Reducing markers does not necessarily lead to a reduction in future events – this disconnect is disappointing.
  • Statins remain the gold standard for chronic therapy, but the mechanism is not completely understood.
  • LDL reduction is crucial for improved prognosis.
  • CRP may not be the optimal tool to assess risk of inflammation.
  • We need new therapies for plaque inflammation, but for now statins remain the gold standard for chronic therapy. Almost all new therapies have failed in the last 1-2 years and by and large most trials have been disappointing.
  • Better biomarkers and direct coronary imaging to detect vulnerable patients / lesions may help to develop new modalities.

What are the Gaps in the current knowledge?

  • Our main question today: “How important is plaque inflammation as a modifiable risk factor?”
  • LpPLA2 and SPLA2 therapies have failed – what are the biomarkers that should be targeted?
  • Will HDL-c raising therapies reduce plaque inflammation and CV risk? – or will any benefits be purely lipid related?
  • How are the animal models going to be translated to humans?
  • Is the statin benefit pliotropic or only due to LDL reduction?
  • What new tools exist to assess coronary inflammation burden?
  • We need to understand the most relevant targets / biomarkers, conduct the right clinical trials and study correct pre-clinical models to select the best candidate therapies for plaque inflammation.
  • However, we need to remember that the inflammatory cascade is very complex and it would be naive to think that blocking a single pathway will be effective as a magic bullet.

Our Summary and Recommendations:

  • New targets and therapies need to be pursued in future research. Plaque specific and selective biomarkers need to be established.
  • Imaging modalities need to be developed (PET/CT, PET/MRI, IVUS/NIRS) and we must look beyond inflammation for targets for novel therapies with lowest CV risk.
  • We must also look beyond lipids into infrared technologies to assess therapies and vulnerable plaques and patients.
  • Outcome trial of Apo1 Milano study and PCSK-9 inhibitory studies may improve our understanding in the role of inflammation and coronary atherosclerosis.
  • At the same time we look toward new therapies and solutions, we must use proven therapies such as statins to understand the appropriate biomarkers / models / imaging to gain proof of concept. We must use this information to develop an algorithm for selecting new drugs and assess which targets to aim for.