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Key Clinical Updates in Treatment of High LDL Cholesterol

There remains controversy about the efficacy of omega-3 therapies, since the 2020 STRENGTH trial showed no CVD benefit of omega-3 carboxylic acids; it remains unclear if this result was due to a different omega-3 fatty acid preparation, chance, or a much smaller benefit of omega-3 fatty acids preparations than originally demonstrated.

Bempedoic acid lowers LDL approximately 17–20% on top of moderate to high intensity statins. Similar to statins, bempedoic acid targets cholesterol synthesis in the liver; bempedoic acid inhibits adenosine triphosphate citrate lyase, an enzyme that is upstream of the mechanism of statins (inhibition of HMG-CoA reductase).

Bempedoic acid is also marketed in combination with ezetimibe; this combination provides approximately 38% LDL reduction on top of background lipid-lowering therapy.

Treatment with bempedoic acid may mildly decrease both high sensitivity C-reactive protein (hsCRP) and the risk of diabetes.

Bemepdoic acid also appears to modestly increase the risk of tendon rupture.

Bemepdoic acid should not be used with more than 20 mg of simvastatin daily or 40 mg of pravastatin daily.

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).

Pappa  E  et al. Cardioprotective properties of HDL: structural and functional considerations. Curr Med Chem. 2020;27:2964.
[PubMed: 30714519]  
van der Vorst  EPC. High-density lipoproteins and apolipoprotein A1. Subcell Biochem. 2020;94:399.
[PubMed: 32189309]  


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.


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