Cholesterol-lowering drugs: New active ingredients help with extreme values

People with congenital hypercholesterolemia are particularly at risk of cardiovascular disease. Extremely high cholesterol levels cannot be adequately controlled with statins. The new PCSK9 inhibitors promise relief, but they are extremely expensive.

heart attack and stroke at a young age – this is the threat to patients with familial, i.e. genetically determined, very high cholesterol levels. In these patients, the receptors for LDLcholesterol (Low Density Lipoprotein) to the Liver cells and the LDL concentration in the blood rises dramatically. LDL values ​​even beyond 500 mg/dl are possible.

The statins commonly used to treat disorders of lipid metabolism are often not effective enough. In such cases, they cannot sufficiently reduce LDL cholesterol levels to the desired target levels. In addition, statins cause severe muscle pain as a side effect in many patients, so that treatment must be discontinued.

PCSK9 inhibitors against extremely high cholesterol levels

Two new active substances that have been approved in Germany since 2015 promise relief for high-risk patients with extremely high cholesterol levels. “Evolocumab and Alirocumab are so-called PCSK9 inhibitors and intervene in the elimination of LDL cholesterol,” says Dr. Reinhold Lunow, medical director of Praxisklinik Bornheim near Cologne and Bonn.

PCSK9 (proprotein convertase subtilisin/kexin type 9) is a protein. If its concentration in the blood is too high, it attaches itself to the LDL receptors on the liver cells (hepatocytes). Normally, LDL cholesterol circulating in the blood binds to these receptors and is then absorbed and broken down by the liver cell. The receptor then has two basic options: either it is also broken down or it returns to the cell surface and then binds more LDL cholesterol.

PCSK9 causes the receptor to be degraded and not return to the cell surface. This reduces the number of LDL receptors and increases the LDL level in the blood.

This is where the new PCSK9 inhibitors come into play: They dock onto the enzyme PCSK9 and prevent it from binding to the LDL receptors. These remain free and can therefore continue to bind LDL cholesterol. The new active ingredients therefore inhibit the breakdown of the LDL receptors.

Cholesterol treatment: PCSK9 inhibitors as an injection

Unlike statins, the new drugs are not available as tablets, but must be injected using a small pre-filled syringe. One injection is enough for 14 days.

Initial studies show that even the highest LDL cholesterol levels can be reduced by up to 60%. The new active ingredients are therefore also suitable for patients who have to undergo regular blood purification (lipid apheresis) to reduce their LDL cholesterol levels.

The same applies to high-risk patients in whom the cholesterol for example after a Heart attack cannot be set to a sufficiently low value.

However, the new PCSK9 inhibitors are very expensive with treatment costs of €750 per month and thus cost up to 100 times more than conventional cholesterol lowering agent.

Detecting elevated cholesterol at a young age

“Mutations in the PCSK9 gene represent a major cause of hypercholesterolemia which in turn is one of the most common genetic disorders in Germany," explains Dr. Lunow. However, it is estimated that only 15% of cases are diagnosed. Typically, it is only a heart attack at a young age that prompts research into the cause.

The internist and specialist in diagnostics and preventive medicine therefore recommends: “Even young people should have Dyslipidemia excluded or their cause investigated. Early detection Diagnosis helps prevent arteriosclerosis and cardiovascular diseases."