The severe hypercholesterolaemia can be recognised when
low density lipoprotein cholesterol (
LDL-C) serum levels are equal to or above 5 mmol/L (≥ 190 mg/dL). The prevalence of
LDL-C ≥ 5 mmol/L is 3.8% in Polish population aged 18-79 years. Among these adults there are patients with familial hypercholesterolaemia (FH). According to meta-analysis of 6 Polish population surveys prevalence of heterozygous FH (HeFH) diagnosed using Dutch
Lipid Clinic criteria is 0.4% (95% Cl 0.28-0.53%) in men and women aged 20-74 years, i.e. one in every 250 people. As HeFH is a wellknown cause of premature
coronary heart disease the rigorous treatment targets for
LDL-C have been established in clinical guidelines. Their achievements, even with a high dose of high efficacy
statin therapy is difficult or even impossible. New strong hypolipidaemic drugs i.e.
PCSK9 inhibitors have been initiated against this chalange. Both drugs,
evolocumab and
alirocumab, have been extensively studied in numerous phase 2 and phase 3 trials. Fewer studies with
bococizumab are available until now. The
PCSK9 inhibitors, as monotherapy as well in combination with
statins were associated with mean
LDL-C reduction about 60%. It means that the majority of patients (70-90%) with severe hypercholesterolaemia (including HeFH), treated with
statins, after addition of
PCSK9 inhibitors were able to achieve an
LDL-C < 2.5 mmol/L (< 100 mg/dL) or < 1.8 mmol/L (< 70 mg/dL) level. Another group of patients who may benefit from
PCSK9 inhibitors include those who need
lipid lowering
therapy, but who are
statin intolerant, especially because of
statin-associated muscle symptoms (
SAMS). In our statement we have accepted the diagnosis of
SAMS proposed recently by European
Atherosclerosis Society. Today the longest clinical trial with
evolocumab (11 months) was the open OSLER study, and with
alirocumab ODYSSEY LONG TERM (78 weeks). In the first one the reduction of cardiovascular events by 53% (95% Cl 22-72%) was observed, and in the second one by 48% (10-69%). Neurocognitive events were reported more frequently with both drugs than with placebo. This adverse effect will be the subject of observation in ongoing studies. We still await the results of 4 ongoing large placebo controlled phase 3 trials investigating whether
PCSK9 inhibitors on background of
statin therapy reduce cardiovascular events. Meanwhile
evolocumab, as well as
alirocumab have been accepted to use in clinical practice by European Medicine Agency. In this situation the experts of Polish Society of Cardiology have prepared the statement on the use
PCSK9 inhibitors with indication in the first place for HeFH patients,
statin intolerant and those at high risk who are not able to reach
LDL-C target level with a high potent high dose
statin.