ey among potential targets to reduce this residual cardiovascular risk is atherogenic dyslipidaemia, defined as high triglyceride (TG)-rich lipoproteins and their remnants with low levels of high-density lipoprotein cholesterol (HDL-C). Atherogenic dyslipidaemia is common in people with type 2 diabetes and/or in those who are overweight. According to IAS President Professor Raul Santos: "Atherogenic dyslipidaemia is implicated in residual cardiovascular risk. However, current treatment options are limited due to safety issues and interactions with other drugs."

To find an answer, experts took a "precision medicine" approach in which they synthesised and screened more than 1,300 compounds before identifying a novel agent with SPPARM-alpha activity, pemafibrate. "Because pemafibrate activates and represses a unique set of genes, it has higher potency and selectivity compared with fibrates, traditional non-selective PPAR-alpha agonists," said Professor Jean-Charles Fruchart, President of the R3i Foundation.

In phase 1 and 2 clinical trials, pemafibrate improved all markers of atherogenic dyslipidaemia, reducing TG by up to 50 per cent and remnant cholesterol, a causal cardiovascular risk factor, by up to 80 per cent. Pemafibrate also lowered inflammatory markers, such as C-reactive protein. Importantly, pemafibrate did not show adverse effects on the liver or kidneys, and did not increase serum creatinine. "These trials clearly show a superior benefit versus risk profile for pemafibrate over fibrates in a wide range of patients including those with chronic kidney disease," commented Professor Tatsuhiko Kodama, The University of Tokyo, Japan, a key investigator in these trials.

Pemafibrate also attenuated atherosclerotic lesion development in preclinical studies. Professor Shizuya Yamashita, President of the Japanese Atherosclerosis Society, said: "Based on all the evidence, pemafibrate may offer a new approach for reducing residual cardiovascular risk in high-risk patients with atherogenic dyslipidaemia, especially those with type 2 diabetes."

This is exactly what the PROMINENT (Pemafibrate to Reduce cardiovascular OutcoMes by reducing triglycerides IN diabetic patiENTs) study aims to answer. This international trial is testing whether reducing TG-rich lipoproteins with pemafibrate reduces cardiovascular events in 10,000 high-risk patients with type 2 diabetes, already treated with a statin. Unlike previous fibrate trials, PROMINENT specifically targets individuals with type 2 diabetes and atherogenic dyslipidaemia receiving current standard-of-care concomitant therapy, including effective statin treatment. "The scientific community eagerly awaits results from PROMINENT, due in 4-5 years, to determine if the translation of the SPPARM-alpha concept to the clinic can improve cardiovascular outcomes," said Professor Peter Libby, Harvard Medical School & Brigham and Women's Hospital, USA.