MILAN and BASEL, Switzerland Sept. 3, 2019 AsiaNet /PRNewswire/ --
A new highly selective treatment, a peroxisome proliferator-activated receptor alpha modulator (SPPARM-alpha) agonist, may help to address the gap in managing the residual risk of heart attacks and strokes in high-risk patients, according to over 50 world-leading experts from the International Atherosclerosis Society (IAS) and the Residual Risk Reduction Initiative (R3i). This residual cardiovascular risk persists despite guideline-recommended treatments for high blood pressure, cholesterol and glucose. This unmet clinical challenge, the focus of this Joint IAS-R3i Consensus Statement, was discussed in Paris, France on 1 September 2019.
Key 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,"
