Efficiency and problems of statin therapy in patients with heterozygous familial hypercholesterolemia

Familial hypercholesterolemia (FH) is associated with a very high risk of cardiovascular complications and the need for an early aggressive lipid-lowering therapy. The achievement of lipid target levels is often an extremely difficult task in these patients.

Aims: to analyze sex and age structure of ischemic heart disease (IHD) in patients with a definite, possible and probable FH. to assess the degree of achievement of low density lipoprotein cholesterol (LDL-C) target levels in FH patients on statin therapy and complications that occur during therapy; to analyze the adherence of FH patients to statin therapy and reveal the factors which have an influence on it.

Materials and methods: The analysis of IHD clinical characteristics was performed in 253 FH patients from Karelian register, mean age 52.5 years (confidence interval, CI 22.0; 78.0). Using Dutch Lipid Clinic Network Criteria (DLCN), we established the diagnosis of FH as "definite" if the total number of points was more than eight, "probable" - if the number of points was 6-8, "possible" if the number of points was 3-5. The diagnosis was considered to be excluded if the score was less than three. A definite FH was diagnosed in 96 patients. For the evaluation of target LDL-C levels achievement on statin therapy we analyzed data from 191 FH patients (75 males). For the evaluation of adherence to statin therapy Morisky-Green questionnaire was used in 93 definite FH patients.

Results: In the group with a definite FH the incidence of IHD in the age range from 39 to 60 years was higher in women than in men (50% and 39.4%, p > 0.05), in patients older than 60 years IHD was observed in 66.7% of women and 50% of men (p > 0.05). In general, in the group with a definite FH, the frequency of IHD was more than three times higher in the age group over 40 years compared with patients under 40 years. 57% of patients with a definite FH were adherent to lipid-lowering therapy, 16% had partial adherence and no adherence to therapy was documented in 27% of patients. The achievement of LDL-C target levels was 19.2%: 22.6% in definite FH group and 12.5% in possible FH. Smoking and gender were not associated with adherence to statin therapy. Associated factors with increased adherence to statin therapy were age (p = 0.000003), arterial hypertension (OR = 1.90 (1.02; to 3.55), p = 0.044), the history of IHD (OR = 2.99 (1.50; of 5.97) p = 0.002), myocardial infarction (OR = 5.26 (2.03; 13.60), p = 0.0006), myocardial revascularization (OR = 20.3 (2.64; 156.11), p = 0.004) and the fact of target LDL-cholesterol levels achievement (OR = 19.93 (7.03; 56.50), p < 0.0001). The main reason for the non-acceptance of statin therapy for FH patients was the fear of side effects in 87%. The main reasons for stopping current statin intake were myalgia in 12%, an increase in transaminases in 35%, skin rashes in 12%, and high cost in 6%. 29% of patients had made the decision to stop therapy themselves.

Conclusions: the frequency of IHD in FH patients was more than three times higher in the age group over 40 years and was higher in women. In clinical practice statin therapy in FH patients rarely reaches target lipid values, one of the reasons was low adherence to statin therapy.