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Drug treatments of hypertriglyceridaemia Drug treatments of hypertriglyceridaemia Statin treatment may be considered as the first drug of choice for reducing CVD risk in high-risk individuals with hypertriglyceridaemia. Statin treatment is recommended as the first drug of choice for reducing

CVD risk in high-risk individuals with hypertriglyceridaemia [TG >2.3 mmol/L (200 mg/dL)].

Treatment of patients with heterozygous FH Treatment of patients with heterozygous FH Treatment should be considered to aim at reaching an LDL-C <2.6 mmol/L (<100 mg/dL) or in the presence of CVD <1.8 mmol/L (<70 mg/dL). If targets cannot be reached, maximal reduction of LDL-C should be considered using appropriate drug combinations. For FH patients with ASCVD who are at very-high risk, treatment to

achieve at least a 50% reduction from baseline and an LDL-C <1.4 mmol/L (<55 mg/dL) is recommended. If goals cannot be achieved, a drug combination is recommended.

Treatment of patients with heterozygous FH Treatment of patients with heterozygous FH Treatment with a PCSK9 antibody should be considered in FH patients with CVD or with other factors putting them at very-high risk for CHD, such as other CV risk factors, family history, high Lp(a), or statin intolerance. Treatment with a PCSK9 inhibitor is recommended in very-high-risk

FH patients if the treatment goal is not achieved on maximal tolerated statin plus ezetimibe.

Treatment of dyslipidaemias in older adults Treatment of dyslipidaemias in older people Since older people often have comorbidities and have altered pharmacokinetics, lipid-lowering medication should be started at a lower dose and then titrated with caution to achieve target lipid levels that are the same as in younger people. It is recommended that the statin is started at a low dose if there is

significant renal impairment and/or the potential for drug interactions, and then titrated upwards to achieve LDL-C treatment goals.

Lipid-lowering therapy in patients with ACS Lipid-lowering therapy in patients with ACS If the LDL-C target is not reached with the highest tolerated statin dose and/or ezetimibe, PCSK9 inhibitors may be considered on top of lipid-lowering therapy; or alone or in combination with ezetimibe in statin-intolerant patients or in whom a statin is contraindicated. If the LDL-C goal is not achieved after 4 - 6 weeks despite maximal tolerated statin therapy and ezetimibe, addition of a PCSK9 inhibitor

is recommended.

Recommendation grading Class I Class IIa Class IIb Class III New sections • A new section is focused on the utility of non-invasive CV imaging for classification of total CVD risk, with implications for recommended lipid-modifying therapies. • More data are provided on the biology and physiology of lipids and lipoproteins, and on their roles in pathophysiology. Emerging evidence from observational studies, RCTs, and genetic (Mendelian randomization) studies unequivocally showing a causal effect of LDL-C in the development of ASCVD is discussed, and newer evidence regarding the effects of TGs and HDL on ASCVD risk is presented. • New sections describe novel lipid-modifying medications as well as emerging approaches for lowering LDL-C, TGs, and Lp(a). • A new section discusses the inflammation-related risk in very high-risk patients and the potential role of inflammation as a therapeutic target to lower ASCVD risk. • New/revised concepts More intensive reduction of LDL-C across CV risk categories • For secondary prevention in very-high-risk patients, an LDL-C reduction of >_50% from baseline and an LDL-C goal of <1.4 mmol/L (<55 mg/dL) are recommended.

 For patients with ASCVD who experience a second vascular event within 2 years (not necessarily of the same type as the first event) while taking maximally tolerated statin therapy, an LDL-C goal of <1.0 mmol/L (<40 mg/dL) may be considered. • In primary prevention, for individuals at very-high risk but without FH, an LDL-C reduction of >_50% from baseline and an LDL-C goal of <1.4 mmol/L (<55 mg/dL) are recommended. For individuals at very-high risk (that is, with another risk factor but without ASCVD), in primary prevention the same goals for LDL-C lowering should be considered. • For patients at high risk, an LDL-C reduction of >_50% from baseline and an LDL-C goal of <1.8 mmol/L (<70 mg/dL) are recommended. • For individuals at moderate risk, an LDL-C goal of <2.6 mmol/L (<100 mg/dL) should be considered. • For individuals at low risk, an LDL-C goal of <3.0 mmol/L (<116 mg/dL) may be considered. The rationale for the revised, lower LDL-C goals across CV risk categories is discussed, based on a critical synthesis of available evidence from lipid-modifying interventions resulting in reductions in CV risk. Pharmacological LDL-C-lowering strategies The section on pharmacological strategies to lower LDL-C emphasizes the concept that the absolute LDL-C reduction (determined by pre-treatment LDL- C levels and the LDL-lowering efficacy of the medications) dictates the relative risk reduction, which in turn—depending on the baseline CV risk—defines the associated absolute CV risk reduction in individual patients. Risk classification in patients with FH Patients with FH and ASCVD, or another major risk factor, are classified as very-high-risk, and those without known ASCVD and without other risk factors as high-risk. Recommended treatment goals are defined accordingly. Adverse effects of statins The distinction between formal statin myopathy vs. so-called statin-associated muscle symptoms is emphasized, and the discordance in reported frequency of symptoms in RCTs vs. observational studies are critically discussed on the basis of new relevant evidence. Downloaded from academic.oup.com/eurheartj/article/41/1/111/5556353 by guest on 07 October 2026