R3i - The Residual Risk Reduction Initiative

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Reducing vascular complications
of type 2 diabetes:
New targets, new treatments

R3i Meeting Marrakech
Stay tuned!

On 10 and 11 February 2023, The R3i Foundation and the Steering Committee Members had a meeting in Marrakech where we discussed how to reduce vascular complications of type 2 diabetes, among other important topics.

We will soon post videos of the meeting. Stay tuned!

Latest R3i Booklet and Slide kit

PCSK9 as Therapeutic Target

This booklet/slidedeck, the second in the series, focuses on evidence from clinical trials with PCSK9-targeted therapeutics.

Elevated LDL cholesterol is established as causal for atherosclerotic cardiovascular disease. Statin treatment, although effective in lowering LDL cholesterol, still leaves an unacceptably high residual cardiovascular risk, underlining the need for additional therapies.

VIEW THE SLIDEKIT

R3i Editorial

6 December 2022

Lipid-related residual risk: lessons from PROMINENT?

Prof. Jean Charles Fruchart, Prof. Michel Hermans, Prof. Pierre Amarenco

Triglyceride-rich lipoproteins have attracted much attention as a likely therapeutic target to reduce residual cardiovascular risk, supported by evidence from extensive epidemiologic, genetic, and mechanistic studies . There are also insights from the fibrate trials suggesting clinical benefit in patients with type 2 diabetes and atherogenic dyslipidemia, i.e., the combination of mild-to-moderate hypertriglyceridemia, and low plasma concentration of high-density lipoprotein cholesterol (HDL-C)...

Landmark studies

6 December 2022

Results from PROMINENT are in

In PROMINENT (Pemafibrate to Reduce Cardiovascular OutcoMes by Reducing Triglycerides IN patiENts With diabetes) lowering triglyceride levels by 26% with pemafibrate on top of intense statin therapy did not significantly reduce cardiovascular events in patients with type 2 diabetes and hypertriglyceridemia. However, exploratory data suggest this treatment may have potential in non-alcoholic fatty liver disease (NAFLD).

Focus on...

6 December 2022

RESPECT-EPA– Randomized Trial for Evaluating Secondary Prevention Efficacy of Combination Therapy - Statin and Eicosapentaenoic Acid

The RESPECT-EPA trial showed a marginally significant effect of highly purified eicosapentaenoic acid (EPA) on the primary outcome (a composite of cardiovascular death, nonfatal myocardial infarction [MI], nonfatal ischemic stroke, unstable angina pectoris, or coronary revascularization). The study did, however, have large dropout and protocol violation rates.

Differentiating SPPARMα and fibrates
(PPARα agonists)

This booklet/slidekit discusses the evidence for the novel SPPARMα agonist, pemafibrate, that differentiates it as a distinct therapeutic class from traditional fibrates.

SSPARMα at the Crossroads of Obesity,
Diabetes and Cardiovascular Diseases

This library discusses the rationale and therapeutic opportunities for SPPARαMs in the future management of cardiovascular diseases, including the latest information on the role of triglyceride-rich lipoproteins and their remnants in residual vascular risk.

PCSK9 and Atherosclerosis

Authors review the discovery and structure of PCSK9, PCSK9 levels in health and disease, PCSK9-drug interactions focusing on statin trials, current approaches to PCSK9 inhibition, and recent results from anti-PCSK9 mAb pre-clinical and clinical trials.

Other Slidekits

The R3i Educational Library also contains numerous commented slides concerning micro and macrovascular residual risk as well as the detailed analysis of the most important clinical studies related to it.

Triglyceride-rich lipoproteins and atherosclerotic cardiovascular disease

This booklet provides a critical background to triglyceride-rich lipoproteins and their role in ASCVD, concluding with discussion of the trials.

PCS9 as a therapeutic target
Insights from clinical trials

This booklet/slidedeck, the second in the series, focuses on evidence from clinical trials with PCSK9-targeted therapeutics.

Recent publications

MESA: Remnant-cholesterol and inflammation associate similarly with cardiovascular risk

MESA (Multi-Ethnic Study of Atherosclerosis) was initiated to study the correlates, predictors, and progression of subclinical cardiovascular disease in a...

Remnant cholesterol: a residual risk factor in Korean diabetes patients

Studies conducted predominantly in Caucasian cohorts show that elevated remnant cholesterol is a risk factor for cardiovascular disease. There is,...

Non-alcoholic fatty liver disease, diabetic retinopathy and atherogenic dyslipidemia

Some reports have suggested that the prevalence of diabetic retinopathy is lower in individuals with concomitant non-alcoholic fatty liver disease...

Matrix metallopeptidase 9: a potential marker of residual risk?

Matrix metallopeptidase 9 (MMP-9) plays a key role in vascular remodelling, development of the atherosclerotic lesion, and arterial plaque rupture,...

NEW

Top 5 Award for the Joint Residual Risk Reduction Initiative (R3i) Foundation/ International Atherosclerosis Society (IAS) Consensus Statement on Selective Peroxisome Proliferator‑Activated Receptor alpha Modulators (SPPARMα)

Cardiovascular Diabetology, the first journal to exclusively cover the link between diabetes and cardiovascular disorders (9.95 2-year impact factor), announced that this landmark paper is in the Top 5 of the most influential articles published.

Editors-in-Chief of Cardiovascular Diabetology Prof. E Fisman and Prof. A Tenenbaum commented: ‘On the occasion of Cardiovascular Diabetology’s 20th anniversary we are delighted to confirm that this is one of most influential articles for the journal. The publication will be showcased in the coming year...’
https://cardiab.biomedcentral.com/articles/10.1186/s12933-019-0864-7

R3i NEW PUBLICATIONS

➤ Selective Peroxisome Proliferator–Activated Receptor Alpha Modulators (SPPARMα): New Opportunities to Reduce Residual Cardiovascular Risk in Chronic Kidney Disease?

➤ Residual vascular risk in diabetes: Will the SPPARMα concept hold the key?

➤ SPPARMα – the Lazarus effect

KEEPING UP TO DATE
WITH THE SSPARMα REVOLUTION

NEW MOVIE - Understanding how pemafibrate acts

What's Residual Risk?

Residual risk of vascular events persisting in patients at treatment goals according to current standards of care or failing to meet goals, including risk related to dyslipidemia, high blood pressure, hyperglycemia, systemic inflammation and unhealthy lifestyles.

What is the Initiative?

The R³i, a worldwide, academic, multidisciplinary non-profit organization, aims to successfully address the excessively high risk of macro- and micro-vascular complications in patients with atherogenic dyslipidemia, characterised by elevated triglycerides and low levels of high-density lipoprotein (HDL) cholesterol and unaddressed by current standards of care.