The selective peroxisome proliferator-activated receptor alpha modulator (SPPARM) paradigm: conceptual framework and therapeutic potential: A consensus statement from the International Atherosclerosis Society (IAS) and the Residual Risk Reduction Initiative (R3i) Foundation


Fruchart J., Santos R. D. , Aguilar-Salinas C., Aikawa M., Al Rasadi K., Amarenco P., ...More

CARDIOVASCULAR DIABETOLOGY, vol.18, 2019 (Journal Indexed in SCI) identifier identifier identifier

  • Publication Type: Article / Review
  • Volume: 18
  • Publication Date: 2019
  • Doi Number: 10.1186/s12933-019-0864-7
  • Title of Journal : CARDIOVASCULAR DIABETOLOGY

Abstract

In the era of precision medicine, treatments that target specific modifiable characteristics of high-risk patients have the potential to lower further the residual risk of atherosclerotic cardiovascular events. Correction of atherogenic dyslipidemia, however, remains a major unmet clinical need. Elevated plasma triglycerides, with or without low levels of high-density lipoprotein cholesterol (HDL-C), offer a key modifiable component of this common dyslipidemia, especially in insulin resistant conditions such as type 2 diabetes mellitus. The development of selective peroxisome proliferator-activated receptor alpha modulators (SPPARM) offers an approach to address this treatment gap. This Joint Consensus Panel appraised evidence for the first SPPARM agonist and concluded that this agent represents a novel therapeutic class, distinct from fibrates, based on pharmacological activity, and, importantly, a safe hepatic and renal profile. The ongoing PROMINENT cardiovascular outcomes trial is testing in 10,000 patients with type 2 diabetes mellitus, elevated triglycerides, and low levels of HDL-C whether treatment with this SPPARM agonist safely reduces residual cardiovascular risk.