Abstract
Familial hypercholesterolemia (FH) is an autosomal disorder characterized by increased
levels of total cholesterol and low density lipoprotein (LDL) cholesterol.
The extent of underdiagnosis and undertreatment of individuals with FH is largely
unknown.
The LDL-lowering capacity of statins in combination with other lipid-lowering drugs
is maximally around 50–60%. FH patients have a strongly elevated LDL-C and in most
cases maximal current treatment is not sufficient to reach the desired LDL targets.
Therefore, FH patients have a large residual cardiovascular risk despite the use of
statins and there is a medical need for new additional drugs to further lower LDL-C
in patients with FH to improve their prognosis.
PCSK9 inhibitors have shown great efficacy in lowering lipids with very few side effects.
No synergism between statins and PCSK9 inhibition was observed in many trials, allowing
clinicians to select a statin dose before considering the initiation of PCSK9-inhibitor
therapy.
In patients with FH, who are at risk for markedly accelerated atherosclerosis and
premature cardiovascular death, also treatment with lomitapide or mipomersen has the
potential to reduce the risk of atherosclerotic cardiovascular disease and premature
mortality.
These new drugs will be probably reserved for the most severely affected FH patients
and could help clinicians to reduce their residual cardiovascular risk.
Key words
familial hypercholesterolemia - PSCK9 inhibitors - evolocumab - alirocumab - mipomersen
- lomitapide