[Modern lipid-lowering drugs-A means to counter the problem of undertreatment?]

An elevated low-density lipoproteincholesterol (LDL-C) level is one of the most important modifiable cardiovascular risk factors. Despite potent combination treatment, the LDL‑C target values are not achieved in many high-risk patients.

Presentation of the rationale for lowering LDL‑C, the current status of lipid-lowering treatment and established and novel approaches to lower LDL‑C.

Based on the large outcome trials with ezetimibe and antibodies against proprotein convertase subtilisin-kexin type 9 (PCSK9), the professional societies recommend LDL‑C target values depending on the individual cardiovascular risk. For patients with manifest atherosclerosis, the LDL‑C target value is < 55 mg/dL (1.4 mmol/L). The LDL‑C target values are only achieved in the minority of patients. The reasons for this include a lack of awareness among treating physicians, low medication adherence, restrictions in prescriptions and intolerance. On the basis of a healthy lifestyle, statins are the cornerstone of LDL-C-lowering treatment. If LDL‑C targets are not achieved, the cholesterol absorption inhibitor ezetimibe is additionally recommended. As a third step, PCSK9 antibodies are added. A novel drug to lower LDL‑C is the orally available bempedoic acid, which acts on the same metabolic pathway as statins but is specifically activated in the liver and not in the skeletal muscle. Another novel drug is inclisiran, which acts as an intracellular PCSK9 inhibitor through RNA interference. Inclisiran is administered subcutaneously only every 6 months and has potential advantages regarding adherence. According to the new recommendations, active substances should be combined and fixed-dose combinations should be used early for lowering of LDL‑C.

Using established and novel LDL-C-lowering drugs, the recommended LDL‑C target values can be achieved in the majority of patients with a high cardiovascular risk.