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......................... 4.6.3. Strategies to control dyslipidaemias The presence of dyslipidaemias secondary to other conditions must be excluded before beginning treatment, as treatment of underlying disease may improve hyperlipidaemia without requiring lipidlowering therapy. This is particularly true for hypothyroidism. Secondary dyslipidaemias can also be caused by alcohol abuse, DM, Cushing’s syndrome, diseases of the liver and kidneys, as well as by drugs (e.g. corticosteroids). In addition, lifestyle optimization is crucial in all patients with higher than optimal lipid levels.

4.6.3.1 Strategies to control low-density lipoprotein cholesterol

4.6.3.1.1. Diet and lifestyle modifications. Dietary factors influence the development of ASCVD, either directly or through their action on traditional risk factors, such as plasma lipids, BP, or glucose levels. Consistent evidence from epidemiological studies indicates that higher consumption of fruit, non-starchy vegetables, nuts, legumes, fish, vegetable oils, yoghurt, and wholegrains, along with a lower intake of red and processed meats, foods higher in refined carbohydrates, and salt, is associated with a lower incidence of CV events.519 Moreover, the replacement of animal fats, including dairy fat, with vegetable sources of fats and PUFAs may decrease the risk of ASCVD.407 More detail on lifestyle recommendations can be found earlier in this section.

4.6.3.1.2. Drugs for treatment of dyslipidaemias. The currently available lipid-lowering drugs include inhibitors of 3-hydroxy-3-methylglutaryl-coenzyme A reductase (statins), fibrates, bile acid sequestrants, selective cholesterol absorption inhibitors (e.g. ezetimibe), and—more recently—PCSK9 inhibitors. Bempedoic acid, an oral cholesterol synthesis inhibitor, has recently been approved in several countries. Usage is mainly intended in combination with ezetimibe in patients with statin intolerance. ASCVD outcome trials are not expected before the end of 2022. Additionally, inclisiran, a new small interfering ribonucleic acid, has shown to reduce LDL-C by 5055% when applied subcutaneously twice a year. These results were obtained either on top of statin or without other lipid-lowering therapies, and with almost no side-effects. Inclisiran has been approved in several European countries. Results from the ASCVD outcomes trial are expected for 2023.

The expected LDL-C reductions in response to therapy are shown in Figure 13, and may vary widely among individuals. Therefore, monitoring the effect on LDL-C levels is recommended, with assessment of LDL-C levels 4 - 6 weeks after any treatment strategy initiation or change.

Treatment Average LDL-C reduction

Intensity of lipid-lowering treatment

Moderate-intensity statin High-intensity statin High-intensity statin plus ezetimibe PCSK9 inhibitor PCSK9 inhibitor plus high-intensity statin PCSK9 inhibitor plus high-intensity statin plus ezetimibe 30%

50% 65% 60% 75% 85%

Figure 13 Expected low-density lipoprotein cholesterol reductions for combination therapies. LDL-C = low-density lipoprotein cholesterol; PCSK9 = proprotein convertase subtilisin/kexin type 9. Adapted from Mach et al.3

Recommendations for pharmacological low-density lipoprotein cholesterol lowering for those <70 years of age (for recommendations for persons aged 70 years, see respective recommendations tables).

Recommendations Classa Levelb

It is recommended that a high-intensity statin is prescribed up to the highest tolerated dose to reach the LDL-C goals set for the specific risk group.21,520,521 I A An ultimatec LDL-C goal of <1.4 mmol/L (55 mg/ dL) and LDL-C reduction of >_50% from baseline should be considered in apparently healthy persons <70 years at very high risk.21,22,522 IIa C An ultimatec LDL-C goal of <1.8 mmol/L (70 mg/dL) and LDL-C reduction of >_50% from baseline should be considered in apparently healthy persons <70 years at high risk.21,22,522 IIa C In patients with established ASCVD, lipid-lowering treatment with an ultimatec LDL-C goal of <1.4 mmol/L (55 mg/dL) and a >_50% reduction in LDL- C vs. baseline is recommended.21,508,515517,522 I A If the goals are not achieved with the maximum tolerated dose of a statin, combination with ezetimibe is recommended.515 I B For primary prevention patients at very high risk, but without FH, if the LDL-C goal is not achieved on a maximum tolerated dose of a statin and ezetimibe, combination therapy including a PCSK9 inhibitor may be considered. IIb C

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