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Key Clinical Updates in Treatment of High LDL Cholesterol

Bempedoic acid, an inhibitor of adenosine triphosphate citrate lyase approved by the FDA in 2020, is a new option for LDL lowering in patients with statin intolerance.

A novel PCSK9 inhibitor called inclisiran uses silencing RNA technology to reduce PCSK9 protein production by the liver to lower LDL cholesterol. It would enable dosing every 6 months.

In 2019, the FDA granted icosapent ethyl a broad indication for CVD event lowering in patients with triglycerides over 150 mg/dL and either established CVD or diabetes mellitus plus two or more additional risk factors for CVD.

In two large pivotal clinical trials, AIM-HIGH and HPS2- THRIVE, extended-release niacin did not reduce cardiovascular events when added to statin therapy in high-risk patients. Therefore, niacin should be used rarely.

The 2019 European Society of Cardiology guidelines have endorsed an LDL cholesterol treatment goal of less than 55 mg/dL in very high-risk patients.

Reduction of LDL cholesterol with statins is just one part of a program to reduce the risk of CVD. Other measures—including diet, exercise, smoking cessation, hypertension control, diabetes control, and antithrombotic therapy—are also of central importance. For example, exercise (and weight loss) may reduce the LDL cholesterol and increase the HDL. Quitting smoking reduces the effect of other cardiovascular risk factors (such as a high cholesterol level); it may also increase the HDL cholesterol level. Modest alcohol use (1–2 ounces a day) also raises HDL levels and may have a salutary effect on CHD rates.

The use of medications to raise the HDL cholesterol has not been demonstrated to provide additional benefit. For example, cholesteryl ester transfer protein inhibitors are a class of medicines being investigated to raise HDL levels; however, agents in this class have not been shown to be effective in so doing. The addition of niacin to statins has also been carefully studied in the AIM-HIGH study and the HPS2-THRIVE study in patients at high risk for CVD and shown not to produce any further benefit (ie, to decrease parameters of cardiovascular risk).

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Zeman  M  et al. Niacin in the treatment of hyperlipidemias in light of new clinical trials: has niacin lost its place? Med Sci Monit. 2015 Jul 25;21:2156–62.
[PubMed: 26210594]

DIET THERAPY

Studies of nonhospitalized adults have reported only modest cholesterol-lowering benefits of individual dietary therapies, typically in the range of a 5–10% decrease in LDL cholesterol, and even less over the long term. The effect of diet therapies, however, may be additive; some patients will have striking reductions in LDL cholesterol—up to a 25–30% decrease—whereas others will have clinically important increases. Thus, the results of diet therapy should be assessed about 4 weeks after initiation.

Several nutritional approaches to diet therapy are available. Most Americans currently eat over 35% of calories as fat, of which 15% is saturated fat. A traditional cholesterol-lowering diet recommends ...

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