Unmet Need for Hypertriglyceridemia Management

Ganda OP, Bhatt DL, Mason RP, Miller M, Boden WE.
Unmet Need for Adjunctive Dyslipidemia Therapy in Hypertriglyceridemia Management. J Am Coll Cardiol 2018;72:330-343.

The following are key points to remember from this review article on the unmet need for adjunctive dyslipidemia therapy in the management of hypertriglyceridemia:

  1. Despite the use of high-intensity statins to reduce the risk of atherosclerotic cardiovascular events, substantial risk remains. This is particularly true among patients with type 2 diabetes mellitus (DM2), metabolic syndrome, and obesity.
  2. Epidemiologic studies have demonstrated that, in addition to elevated low-density lipoprotein cholesterol (LDL-C) levels, elevation in both triglycerides (TGs) and high-density lipoprotein cholesterol (HDL-C) are independent predictors of coronary heart disease (CHD).
  3. Hypertriglyceridemia is a highly prevalent lipid disorder. More than 25% of the adult population has TG levels of ≥150 mg/dl. This is likely to continue increasing with the epidemics of obesity, metabolic syndrome, and DM2.
  4. Two prior randomized trials of statins plus extended-release niacin or placebo failed to show a reduction in CHD events. Three other large randomized trials evaluating cholesteryl ester transfer protein inhibitors also failed to show reductions in atherosclerotic cardiovascular disease risk despite increasing HDL-C levels.
  5. Fibrates, niacin, and omega-3 fatty acids are available therapies that treat elevated TG and/or HDL-C levels. Results have been mixed. Two studies each of omega-3 fatty acid therapy and fibrate therapy have shown reductions in important cardiovascular outcomes (e.g., death, nonfatal myocardial infarction). However, eight other studies of these agents have failed to show benefit.
  6. Inflammation remains an important potential target for therapies aimed at reducing CHD risk. Omega-3 fatty acids may have anti-inflammatory properties, likely via leukotriene-mediated effects. Canakinumab (a monoclonal antibody targeting IL-1β) improved CHD risk among patients with an elevated baseline C-reactive protein.
  7. Several large randomized trials are currently evaluating the role of omega-3 fatty acid therapy for statin-treated patients. Two of these include patients with a baseline LDL-C level <100 mg/dl.
  8. Other potential therapies to address the residual CHD risk include antibody-based antisense oligonucleotides and small interfering ribonucleic acid. These targets are still early in development for cardiovascular patients.

Clinical Topics: Diabetes and Cardiometabolic Disease, Dyslipidemia, Prevention, Hypertriglyceridemia, Lipid Metabolism, Nonstatins, Novel Agents, Statins

Keywords: Antibodies, Monoclonal, Atherosclerosis, Cholesterol Ester Transfer Proteins, Cholesterol, HDL, Cholesterol, LDL, Coronary Disease, C-Reactive Protein, Diabetes Mellitus, Type 2, Dyslipidemias, Fatty Acids, Omega-3, Fibric Acids, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Hypertriglyceridemia, Inflammation, Interleukin-1, Leukotrienes, Metabolic Syndrome X, Myocardial Infarction, Niacin, Obesity, Primary Prevention, Triglycerides, Vascular Diseases

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