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

Fruchart, Jean-Charles;Santos, Raul D;Aguilar-Salinas, Carlos;Aikawa, Masanori;Libby, Peter;et.al.
(2019) Cardiovascular Diabetology — Vol. 18, n° 1, p. 71 (2019)

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Authors
  • Fruchart, Jean-Charles
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  • Santos, Raul D
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  • Aguilar-Salinas, Carlos
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  • Aikawa, Masanori
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  • Hermans, MichelUCLouvain
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  • Libby, Peter
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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 (SPPARMα) offers an approach to address this treatment gap. This Joint Consensus Panel appraised evidence for the first SPPARMα 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 SPPARMα agonist safely reduces residual cardiovascular risk.
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Fruchart, J.-C., Santos, R. D., Aguilar-Salinas, C., Aikawa, M., Al Rasadi, K., Amarenco, P., Barter, P. J., Ceska, R., Corsini, A., Després, J.-P., Duriez, P., Eckel, R. H., Ezhov, M. V., Farnier, M., Ginsberg, H. N., Hermans, M., Ishibashi, S., Karpe, F., Kodama, T., et al. (2019). The selective peroxisome proliferator-activated receptor alpha modulator (SPPARMα) paradigm: conceptual framework and therapeutic potential : A consensus statement from the International Atherosclerosis Society (IAS) and the Residual Risk Reduction Initiative (R3i) Foundation. Cardiovascular Diabetology, 18(1), 71. https://doi.org/10.1186/s12933-019-0864-7 (Original work published 2019)