PracticeUpdate: Cardiology - Winter 2018

EDITOR’S PICKS 16

Unmet Need for Adjunctive Dyslipidemia Therapy in Hypertriglyceridemia Management JACC: Journal of the American College of Cardiology

" The timely and

Take-home message • The authors of this review discuss the role of elevated triglycerides in causing residual risk of atherosclerotic cardiovascular disease events despite the use of high-intensity statins. Previous trials of fibrates, niacin, and most cholesterol ester transfer protein inhibitors did not show additional benefit when added to statin therapy. Omega-3 fatty acids are effective at lowering triglyceride levels and reducing plaque instability, but there is no evidence regarding clinical outcomes available. • There are ongoing randomized controlled trials of various triglyceride-lowering strategies, and the outcomes of these trials will inform future practice. Abstract

thorough review by Ganda et al furnishes a formidable foundation for understanding the state of the art of hypertriglyceridemia management. "

proinflammatory mediators of atherogenesis, clinical outcomes data are currently lacking. Several ongoing randomized controlled trials of TG-lowering strategies with an optimal dosage of omega-3 fatty acids are nearing completion. Unmet Need for Adjunctive Dyslipidemia Ther- apy in Hypertriglyceridemia Management. J Am Coll Cardiol 2018 Jun 16;72(3)330-343, OP Ganda, DL Bhatt, RP Mason, et al. www.practiceupdate.com/c/70885 report soon. They provide a particularly focused discussion on use of omega-3 fatty acids in this regard, as one of the per- tinent trials should report in 2018. Other approaches to management of risk attributable to triglyceride-rich lipo- proteins include deploying a fibric acid derivative, a selective modulator of peroxisome proliferation activation recep- tors-alpha (PPAR-α), to appropriately selected individuals with hypertriglyceri- demia. An antisense oligonucleotide that targets apolipoprotein CIII, an atherogenic and possibly proinflammatory component of triglyceride-rich lipoproteins, also holds considerable clinical promise. The timely and thorough review by Ganda et al furnishes a formidable foundation for understanding the state of the art of hyper- triglyceridemia management. It provides a rich context for understanding trials in pro- gress that may offer a welcome addition to the armamentarium of lipid therapies beyond effective LDL-lowering strate- gies. Such advances will help us manage residual risk in our hypertriglyceridemic patients.

strongly supported by genetic linkage studies. Previous trials with fibrates, niacin, and most cholesterol ester transfer protein inhibitors that targeted high-density lipoprotein cholesterol raising, and/or TG lowering, have failed to show conclusive evidence of incremental event reduc- tion after low-density lipoprotein cholesterol levels were “optimally controlled” with statins. Although omega-3 fatty acids are efficacious in lowering TG levels and may have pleiotropic effects such as reducing plaque instability and dyslipidemia characterized by elevated concentrations of triglyceride-rich lipo- protein particles presents an important and prevalent problem. Particularly, given the epidemics of obesity and diabetes, this aspect of the lipoprotein profile has recently garnered greater concern. Inflam- mation also contributes to cardiovascular risk and has become a therapeutic target in cardiovascular disease. Omega-3 fatty acids may afford a double opportunity to address residual risk, both by lowering triglyceride-rich lipoprotein levels and potentially exerting anti-inflam- matory effects. Although triglyceride-rich lipoproteins are associated with inflam- mation, even to a greater extent than LDL, their atherogenic potential may also arise from traditional lipid delivery mechanisms, such as fostering foam cell formation. The review by Ganda et al presents a com- prehensive, contemporary, and scholarly approach to emerging aspects of man- agement of residual risk attributed to triglyceride-rich lipoproteins in the context of contemporary clinical trials, including those in progress, some of which may

Despite the important role of high-intensity stat- ins in reducing atherosclerotic cardiovascular disease events in secondary and primary preven- tion, substantial residual risk persists, particularly among high-risk patients with type 2 diabetes mellitus, metabolic syndrome, and obesity. Con- siderable attention is currently directed to the role that elevated triglycerides (TGs) and non- high-density lipoprotein cholesterol levels play as important mediators of residual atheroscle- rotic cardiovascular disease risk, which is further COMMENT By Peter Libby MD W e are living through exciting times in cardiovascular pre- vention. Our ability to lower low-density lipoprotein (LDL) with phar- macologic agents permits us to achieve reductions in LDL below those seen in newborns and hunter-gatherer popula- tions unexposed to the contemporary Western fast food environment. Despite this enormous achievement, considera- ble cardiovascular residual risk remains, at least over the time span of pharmaco- logic LDL-lowering in trials. This concern has intensified interest in therapies that might reduce cardiovascular risk beyond LDL reduction. Many pinned hopes on raising high-den- sity lipoprotein (HDL), given the strength of the observational epidemiologic evidence that HDL might protect from car- diovascular disease. Yet, multiple routes to raise HDL have failed to reduce events in contemporary clinical trials, particularly in individuals well-treated with statins. Moreover, human genetic evidence has cast doubt on HDL’s protective properties. Within the lipid profile, the atherogenic

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