DEFINING TOMORROW'S VASCULAR STRATEGIES
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Sep 2021
Residual vascular risk: What matters?
Aug 2021
Understanding vein graft failure: a role for PPARalpha in pathobiology
May 2021
Residual cardiovascular risk: how to identify?
Apr 2021
Metabolic syndrome and COVID-19
Mar 2021
Elevated triglyceride: linking ASCVD and dementia
Feb 2021
Does SPPARMα offer new opportunities in metabolic syndrome and NAFLD?
Jan 2021
Omega-3 fatty acids for residual cardiovascular risk: more questions than answers
Oct 2020
Targeting triglycerides: Novel agents expand the field
Jul 2020
Why multidrug approaches are needed in NASH: insights with pemafibrate
Jun 2020
Triglyceride-rich remnant lipoproteins: a new therapeutic target in aortic valve stenosis?
Mar 2020
Lowering triglycerides or low-density lipoprotein cholesterol: which provides greater clinical benefit?
Feb 2020
The omega-3 fatty acid conundrum
Dec 2019
Focus on stroke: more input to address residual cardiovascular risk
Jul 2019
International Expert Consensus on Selective Peroxisome Proliferator-Activated Receptor Alpha Modulator (SPPARMα): New opportunities for targeting modifiable residual cardiovascular risk
Nov 2018
Residual cardiovascular risk: triglyceride metabolism and genetics provide a key
Jul 2018
The clinical gap for managing residual cardiovascular risk: will new approaches make the difference?
Apr 2018
Residual cardiovascular risk: refocus on a multifactorial approach
Feb 2018
Optimizing treatment benefit: the tenet of personalized medicine
Jan 2018
Addressing residual cardiovascular risk – back to basics?
Dec 2017
Residual risk of heart failure: how to address this global epidemic?
Oct 2017
Remnants and residual cardiovascular risk: triglycerides or cholesterol?
Jul 2017
Targeting residual cardiovascular risk: lipids and beyond…
Jun 2017
Why we need to re-focus on Latin America.
Apr 2017
Residual cardiovascular risk in the Middle East: a perfect storm in the making
Feb 2017
A global call to action on residual cardiovascular risk
Dec 2016
SPPARM?: more than one way to tackle residual risk
Oct 2016
Remnants linked with diabetic myocardial dysfunction
Sep 2016
New study links elevated triglycerides with plaque progression
Aug 2016
Atherogenic dyslipidaemia: a risk factor for silent coronary artery disease
Jul 2016
SPPARM?: a concept becomes clinical reality
Jun 2016
Remnant cholesterol back in the news
May 2016
Back to the future: triglycerides revisited
Apr 2016
Unravelling the heritability of triglycerides and coronary risk
Mar 2016
Will residual cardiovascular risk meet its nemesis in 2016?
Feb 2016
Tackling residual cardiovascular risk: a case for targeting postprandial triglycerides?
Jan 2016
Looking back at 2015: lipid highlights
Dec 2015
Legacy effects in cardiovascular prevention
Nov 2015
Residual cardiovascular risk: it’s not just lipids!
Oct 2015
Addressing residual vascular risk: beyond pharmacotherapy
Sep 2015
Back to basics: triglyceride-rich lipoproteins, remnants and residual vascular risk
Jul 2015
Beyond the PCSK9 decade: what's next?
Jun 2015
Targeting triglycerides: what lies on the horizon for novel therapies?
May 2015
Do we need new lipid biomarkers for residual cardiovascular risk?
Apr 2015
The Residual Risk Debate Hots Up: Lowering LDL-C or lowering remnant cholesterol?
Mar 2015
Call for action on stroke
Feb 2015
Triglycerides: the tide has turned
Jan 2015
Post IMPROVE-IT: Where to now for residual risk?
Dec 2014
R3i publishes new Call to Action paper: Residual Microvascular Risk in Type 2 Diabetes in 2014: Is it Time for a Re-Think?
Sep 2014
Targeting residual vascular risk: round-up from ESC Congress 2014 and beyond
Jul 2014
Lipid-related residual cardiovascular risk: a new therapeutic target on the horizon
Mar 2014
Non-HDL-C and residual cardiovascular risk: the Lp(a) perspective
Feb 2014
REALIST Micro, atherogenic dyslipidaemia and residual microvascular risk
Jan 2014
Looking back at 2013: what have we learned about residual vascular risk?
Dec 2013
Long-overdue US guidelines for lipid management oversimplify the evidence
Nov 2013
Triglycerides and residual cardiovascular risk: where now?
Oct 2013
How to target residual cardiovascular risk?
Sep 2013
The Residual Vascular Risk Conundrum: Why we should target atherogenic dyslipidaemia
Jul 2013
Targeting atherogenic dyslipidemia: we need to do better
Apr 2013
Is PCSK9- targeted therapy the new hope for residual risk?
Mar 2013
Scope for multifocal approaches for reducing residual cardiovascular risk?
Feb 2013
Renewing the R3i call to action: Now more than ever we need to target and treat residual cardiovascular risk
Jan 2013
Time for a re-think on guidelines to reduce residual microvascular risk in diabetes?
Jan 2013
Addressing the residual burden of CVD in renal impairment: do PPARa agonists provide an answer?
Jan 2013
Re-evaluating options for residual risk post-HPS2-THRIVE : are SPPARMs the answer?
Dec 2012
Dysfunctional HDL: an additional target for reducing residual risk
Nov 2012
Egg consumption: a hidden residual risk factor
Oct 2012
Call to action: re-emphasising the importance of targeting residual vascular risk
Jun 2012
Time to prioritise atherogenic dyslipidaemia to reduce residual microvascular risk?
Jan 2012
Residual vascular risk in chronic kidney disease: an overlooked high-risk group
Dec 2011
Introducing the HDL Resource Center: HDL science now available for clinicians
Oct 2011
Targeting reverse cholesterol transport: the future of residual vascular risk reduction?
Sep 2011
After SPARCL: Targeting cardio-cerebrovascular metabolic risk and thrombosis to reduce residual risk of stroke
Jul 2011
Challenging the conventional wisdom: Lessons from the FIELD study on diabetic nephropathy
Jul 2010
ACCORD Eye Study: a milestone in residual microvascular risk reduction for patients with type 2 diabetes
May 2010
Lipids and residual risk of coronary heart disease in statin-treated patients
Mar 2010
ACCORD Lipid Study brings new hope to people with type 2 diabetes and atherogenic dyslipidemia
Mar 2010
Reducing residual risk of diabetic nephropathy: the role of lipoproteins
Dec 2009
ARBITER 6-HALTS: Implications for residual cardiovascular risk
Nov 2009
Microvascular event risk reduction in type 2 diabetes: New evidence from the FIELD study
Aug 2009
Fasting versus nonfasting triglycerides: Importance of triglyceride-regulating genetic polymorphisms to residual cardiovascular risk
Jul 2009
Residual risk of microvascular complications of diabetes: is intensive multitherapy the solution?
Apr 2009
Reducing residual vascular risk: modifiable and non modifiable residual vascular risk factors
Jan 2009
Micro- and macrovascular residual risk: one of the most challenging health problems of the moment
Nov 2008
Treated dyslipidemic patients remain at high residual risk of vascular events

R3i Editorial

2 November 2021
New ACC guidance addresses unmet clinical needs for high-risk patients with mild to moderate hypertriglyceridemia
Prof. Jean Charles Fruchart, Prof. Michel Hermans, Prof. Pierre Amarenco
An Editorial from the R3i Trustees
 
Prof. Jean Charles Fruchart, Prof. Michel Hermans, Prof. Pierre Amarenco For too long, triglycerides (TG) have been the forgotten player in atherosclerotic cardiovascular disease (ASCVD). Times are now changing. Substantive evidence from epidemiologic surveys and Mendelian randomization studies supports a role for TG-rich lipoproteins and their remnants in the causal pathway of ASCVD 1,2. Added to this, REDUCE-IT (Reduction of Cardiovascular Events with Icosapent Ethyl-Interventional Trial) showed that lowering elevated TG with high-dose icosapent ethyl, an eicosapentaenoic acid (EPA) ethyl ester, significantly reduced cardiovascular events in high-risk patients 3. Controversy persists, however, as other clinical trials, including STRENGTH (A Long-Term Outcomes Study to Assess Statin Residual Risk Reduction with Epanova in High Cardiovascular Risk Patients with Hypertriglyceridemia) with a mixed omega-3 fatty acid formulation 4, did not show any cardiovascular benefit from lowering TG. It is, however, recognized by both European and North American guideline groups that elevated TG contribute to increased cardiovascular risk. For example, preceding REDUCE-IT, the 2018 American Heart Association/American College of Cardiology/multisociety cholesterol guideline categorized elevated TG as a “risk-enhancing factor” 5. The 2019 European Society of Cardiology/ European Atherosclerosis Society (ESC/EAS) dyslipidemia guidelines also recommended desirable TG levels in managing elevated TG 6.

Recently, the ACC published an Expert Consensus Decision Pathway on the Management of ASCVD Risk Reduction in Patients With Persistent Hypertriglyceridemia 7 to address gaps in the management of high-risk patients with mild to moderate hypertriglyceridemia (defined as fasting TG ≥150 mg/dL or nonfasting TG ≥175 mg/dL and <500 mg/dL). Specifically, this focused on therapeutic approaches when guideline-recommended lifestyle intervention and a stable dose of maximally tolerated statin therapy have failed to lower elevated TG. For ASCVD patients with persistent mild to moderate hypertriglyceridemia, treatment strategies are differentiated by LDL-C levels. For those with LDL-C levels <70 mg/dL on a statin, a TG-risk-based approach is recommended, with the use of high-dose icosapent ethyl. In contrast, for patients with LDL-C levels ≥100 mg/dL the approach is LDL-C-based, with optimization of statin therapy and consideration of non-statin LDL-lowering options. A joint strategy is recommended if LDL-C levels are between 70 and 99 mg/dL. This consensus document also considered the management of primary prevention patients with diabetes mellitus and persistent hypertriglyceridemia, as well as those with no ASCVD or diabetes mellitus and elevated TG levels. While there is some consistency with European recommendations, the latter do also take account the potential for microvascular benefits from other TG-lowering therapy 6,8.

Why is this new guidance important? This document addresses many uncertainties that clinicians have in their daily management of patients with mild to moderate hypertriglyceridemia. The Editors welcome clarity on managing elevated TG, given the ongoing clinical development of several novel agents that lower TG. Not only do these include the selective peroxisome proliferator-activated receptor alpha agonist pemafibrate, currently being tested in the PROMINENT (Pemafibrate to Reduce Cardiovascular OutcoMes by Reducing Triglycerides IN patients With diabetes) study 9, but also RNA interference therapy (antisense oligonucleotides and small interfering RNAs) and monoclonal antibody therapy specific to key targets of TG metabolism. Results from these trials will be crucial to delineating the contribution of elevated TG – a surrogate for TG-rich lipoproteins and their remnants – to residual cardiovascular risk.

References

1. Do R, Willer CJ, Schmidt EM, et al. Common variants associated with plasma triglycerides and risk for coronary artery disease. Nat Genet 2013;45:1345–52.
2. Nordestgaard BG. Triglyceride-rich lipoproteins and atherosclerotic cardiovascular disease: new insights from epidemiology, genetics, and biology. Circ Res 2016;118:547-63.
3. Bhatt DL, Steg PG, Miller M, et al. Cardiovascular risk reduction with icosapent ethyl for hypertriglyceridemia. N Engl J Med 2019;380:11–22.
4. Nicholls SJ, Lincoff AM, Garcia M, et al. Effect of high-dose omega-3 fatty acids vs corn oil on major adverse cardiovascular events in patients at high cardiovascular risk: the STRENGTH randomized clinical trial. JAMA 2020;324:2268–80.
5. Grundy SM, Stone NJ, Bailey AL, et al. 2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA guideline on the management of blood cholesterol: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. J Am Coll Cardiol 2019;73:e285–e350.
6. Mach F, Baigent C, Catapano AL, et al. 2019 ESC/EAS Guidelines for the management of dyslipidaemias: lipid modification to reduce cardiovascular risk. Eur Heart J 2020;41:111-88.
7. Virani SS, Morris PB, Agarwala A et al. 2021 ACC Expert Consensus Decision Pathway on the Management of ASCVD Risk Reduction in Patients With Persistent Hypertriglyceridemia. A Report of the American College of Cardiology Solution Set Oversight Committee. J Am Coll Cardiol 2021:S0735-10972105323-7. doi: 10.1016/j.jacc.2021.06.011.
8. Averna M, Banach M, Bruckert E, et al. Practical guidance for combination lipid-modifying therapy in high- and very-high-risk patients: A statement from a European Atherosclerosis Society Task Force. Atherosclerosis 2021;325:99-109.
9. Pradhan AD, Paynter NP, Everett BM, et al. Rationale and design of the Pemafibrate to Reduce Cardiovascular Outcomes by Reducing Triglycerides in Patients with Diabetes (PROMINENT) study. Am Heart J 2018;206:80-93.