International Atherosclerosis Society Residual Risk Reduction Initiative Publish Consensus Statement on New Treatment for Residual Cardiovascular Risk

Food and Healthcare Press Releases Tuesday September 3, 2019 09:15
MILAN and BASEL, Switzerland--6 Sep--PRNewswire/InfoQuest

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," 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.

ABOUT THE IAS

The International Atherosclerosis Society (IAS) is a federation of member scientific societies from across the globe. The core mission of the IAS is to promote scientific understanding of the aetiology, prevention, and treatment of atherosclerosis. The IAS coordinates the exchange of scientific information among constituent societies, fosters research into how atherosclerosis develops, and helps translate this knowledge to improving the effectiveness of programmes designed to prevent and treat the disease.

ABOUT THE R3i

The R3i (Residual Risk Reduction Initiative) is a worldwide, academic, multidisciplinary non-profit organisation. Its core objective is to successfully address the excessively high risk of cardiovascular and microvascular complications that persists in patients who are already receiving the current standards of care to address abnormal lipid levels. The R3i is working to achieve this with an innovative global initiative of academic research, education and advocacy.

Related Links
https://www.athero.org/
https://www.r3i.org/
https://cardiab.biomedcentral.com/articles/10.1186/s12933-019-0864-7
https://clinicaltrials.gov/ct2/show/NCT03071692
References

Fruchart JC. et al. The selective peroxisome proliferator-activated receptor alpha modulator (SPPARMα) paradigm: conceptual framework and therapeutic potential. A consensus statement from the IAS and the R3i Foundation. Cardiovasc Diabetology (2019) 18:71.

Contact: info@r3i.org

Latest Press Release

Menarini: Elcin Barker Ergun Group CEO

"Elcin Barker Ergun is the ideal addition to the Menarini team, in order to continue the agenda of growth in geography and therapeutic areas," commented Eric Cornut, Chairman of Menarini. Elcin Barker Ergun: "Menarini is a company admired on a global...

Strekin AG Announces Completion of Patient Recruitment in the RESTORE Phase 3 Clinical Study of STR001

Strekin AG (www.strekin.com), a biopharmaceutical company focused on treatments for hearing loss, announced today that it has successfully completed patient recruitment in the RESTORE study, an international, randomized, placebo-controlled, Phase 3...

Merck Announces FDA Breakthrough Therapy Designation for Investigational Therapy Tepotinib in Patients with Metastatic NSCLC with METex14 Skipping Alterations

- Investigational oral MET inhibitor has previously received SAKIGAKE 'fast-track' regulatory designation in Japan - MET exon 14 skipping alterations and MET amplifications are present in 3-5% of non-small cell lung cancer patients and correlate with...

Updated Results for Investigational Therapy Tepotinib Presented at WCLC 2019

- Results include progression-free survival and overall survival data from Phase Ib/II INSIGHT study - Phase II INSIGHT 2 study now open for enrollment for patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) with epidermal...

Newly Published ROSacea COnsensus (ROSCO) Expert Recommendations Encourage Dermatologists to Upweight Burden-related Discussions, Aim For #Complete Clearance# of Symptoms and Consider Combination Therapy For Severe Patients

Experts also welcome upsurge in the adoption of a rosacea signs and symptoms ('phenotype') led approach in clinical practice and announce the launch of prototype clinical tools to support physicians to optimize rosacea management Published online in the...

Related Topics