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NEW The R3i International Steering Committee Meeting, Marrakech 2023
Reducing vascular complications of type 2 diabetes: New targets, new treatments
▷ Watch SESSION 1 & 2 Webcasts
Latest R3i Booklet and Slidekit
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.
R3i Editorial
26 September 2023
Remnant cholesterol – evolving evidence
Prof. Jean Charles Fruchart, Prof. Michel Hermans, Prof. Pierre Amarenco
Remnant cholesterol continues to attract attention as a target to reduce residual cardiovascular risk. Conventionally, remnant cholesterol is defined as the cholesterol contained in remnant lipoprotein particles, i.e. metabolized very-low-density lipoprotein and intermediate-density lipoprotein in the fasting state, to which is added the cholesterol in chylomicron remnants in the postprandial. There is strong evidence from mechanistic, observational and genetic studies to support a causal association between remnant cholesterol and risk for atherosclerotic cardiovascular disease (ASCVD).
This month’s Landmark study adds to this evidence. In a Mendelian randomization study in over 900,000 subjects, each 1 standard deviation increase in remnant cholesterol increased the risk of myocardial infarction by more than 50%, independent of low-density lipoprotein cholesterol.
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Landmark studies
26 September 2023
More evidence linking remnant cholesterol and cardiovascular outcomes
This Mendelian randomization study including more than 900,000 subjects showed a robust genetic causal association between remnant cholesterol and cardiovascular outcomes.
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Focus on...
26 September 2023
Managing remnant cholesterol: consider both accumulation and visit variability
According to this study from China, the combination of higher cumulative remnant cholesterol and greater remnant cholesterol variability exacerbates the independent risk of carotid atherosclerosis in the general population.
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R3i Booklets / Slidekits Educational Library
Created by Prof. Jean-Charles Fruchart and R3i Members
More than 6.000 downloadable slides
Including printable extensive comments booklets
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
Proteomics: a tool for developing targeted therapies in high-risk patients?

Plasma proteomics has gained focus in the search for targeted therapies, enabling better patient stratification and prediction of treatment response,...
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News from the SUSTAIN 6 and PIONEER 6 trials with semaglutide

The SUSTAIN 6 and PIONEER 6 trials showed cardiovascular benefit with semaglutide, a glucagon-like peptide-1 (GLP-1) receptor agonist in type...
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Pemafibrate in non-alcoholic fatty liver disease

While both pemafibrate and sodium glucose cotransporter-2 (SGLT2) inhibition can decrease serum transaminase levels in patients with non-alcoholic fatty liver...
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Higher remnant cholesterol linked with bioprosthetic valve degeneration

Valve replacement surgery is the first‐line therapy for patients with valvular heart disease. Bioprosthetic heart valves are increasingly becoming the...
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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...’
➤ 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
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.
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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.
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