The Present and Future
JACC Review Topic of the Week
Unmet Need for Adjunctive Dyslipidemia Therapy in Hypertriglyceridemia Management

https://doi.org/10.1016/j.jacc.2018.04.061Get rights and content
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Abstract

Despite the important role of high-intensity statins in reducing atherosclerotic cardiovascular disease events in secondary and primary prevention, substantial residual risk persists, particularly among high-risk patients with type 2 diabetes mellitus, metabolic syndrome, and obesity. Considerable attention is currently directed to the role that elevated triglycerides (TGs) and non–high-density lipoprotein cholesterol levels play as important mediators of residual atherosclerotic cardiovascular disease risk, which is further 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 reduction 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 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.

Key Words

clinical trials
dyslipidemia and residual risk
hypertriglyceridemia
omega-3 fatty acids

Abbreviations and Acronyms

ANGPTL
angiopoietin-like protein
apo
apolipoprotein
ASCVD
atherosclerotic cardiovascular disease
CETP
cholesteryl ester transfer protein
CHD
coronary heart disease
CI
confidence interval
CRP
C-reactive protein
DHA
docosahexaenoic acid
EPA
eicosapentaenoic acid
HDL-C
high-density lipoprotein cholesterol
HR
hazard ratio
IL
interleukin
LDL-C
low-density lipoprotein cholesterol
OM3FA
omega-3 fatty acids
OR
odds ratio
RCT
randomized controlled trial
RR
relative risk
T2DM
type 2 diabetes mellitus
TG
triglyceride

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Dr. Ganda is partially supported by the National Institute of Diabetes and Digestive and Kidney Diseases grant no. P30-DK036836; has served as a consultant/advisory board member for Sanofi-Regeneron, Amarin, Merck, and Novo Nordisk; has received honoraria from Merck, Novo Nordisk, and Sanofi-Regeneron; and has received a research grant from Amarin Pharma. Dr. Bhatt has served on the advisory board for Cardax, Elsevier PracticeUpdate Cardiology, Medscape Cardiology, and Regado Biosciences; has served on the board of directors for Boston VA Research Institute and Society of Cardiovascular Patient Care; chair for the American Heart Association Quality Oversight Committee; member of the data monitoring committees for the Cleveland Clinic, Duke Clinical Research Institute, Harvard Clinical Research Institute, Mayo Clinic, Mount Sinai School of Medicine, and Population Health Research Institute; has received honoraria from the American College of Cardiology (senior associate editor, Clinical Trials and News, ACC.org), Belvoir Publications (Editor-in-Chief, Harvard Heart Letter), Duke Clinical Research Institute (clinical trial steering committees), Harvard Clinical Research Institute (clinical trial steering committee), HMP Communications (Editor-in-Chief, Journal of Invasive Cardiology), Journal of the American College of Cardiology (guest editor, associate editor), Population Health Research Institute (clinical trial steering committee), Slack Publications (chief medical editor, Cardiology Today’s Intervention), Society of Cardiovascular Patient Care (secretary/treasurer), and WebMD (CME steering committees); Clinical Cardiology (deputy editor), NCDR-ACTION Registry Steering Committee (chair), VA CART Research and Publications Committee (chair); has received research funding from Abbott, Amarin (including for his role as chair and principal investigator of REDUCE-IT [Reduction of Cardiovascular Events With Icosapent Ethyl–Intervention] trial), Amgen, AstraZeneca, Bristol-Myers Squibb, Chiesi, Eisai, Ethicon, Forest Laboratories, Ironwood, Ischemix, Lilly, Medtronic, Pfizer, Regeneron, Roche, Sanofi-Aventis, and The Medicines Company; has received royalties from Elsevier (editor, Cardiovascular Intervention: A Companion to Braunwald’s Heart Disease); has served as site co-investigator for Biotronik, Boston Scientific, St. Jude Medical (now Abbott), and Svelte; has served as a trustee for the American College of Cardiology; and unfunded research for FlowCo, Merck, PLx Pharma, and Takeda. Dr. Mason has received grant/research support from Amarin, Amgen, Pfizer, and Novartis; and provides speaking and consultancy services (including receipt of honoraria) for Pfizer and Amarin Pharma Inc.; Dr. Mason donates all honoraria to charity. Dr. Miller has served on an American College of Cardiology, nutrition workgroup (JACC: Section Editor, Clinical Trials and Registries); American Heart Association, Chair, ATVB Council on Clinical Lipidology; member, Council on Lifestyle and Cardiometabolic Health; Akcea Therapeutics, consultant; Amarin, consultant and advisor, steering committee member of REDUCE-IT trial; AstraZeneca, trustee, Connection for Cardiovascular Health Foundation; and author, “Heal Your Heart” (Rodale Press) (author royalties donated to the American Heart Association). Dr. Boden has received research grant support from Clinical Trials Network, Massachusetts Veterans Epidemiology, Research, and Information Center (MAVERIC), VA New England Healthcare System, NHLBI as national co-principal investigator for the ISCHEMIA Trial, Axio Research, Inc., AbbVie, Amarin Pharmaceuticals. Inc., Amgen, AstraZeneca, and Sanofi; has served on the board of directors for Boston VA Research Institute, Inc., CardioDx; has served on the data monitoring committee for VA Cooperative Studies Program; was national coordinator for the STRENGTH Trial, with honoraria from the Cleveland Clinic Clinical Coordinating Center; and has received speaking honoraria from Amgen, Aralez Pharmaceuticals, AstraZeneca, Janssen/Johnson & Johnson, and Regeneron.

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