Background and Aims

Familial hypercholesterolemia (FH) is an autosomal dominant disease that leads to cardiovascular disease. We evaluate the relationship between genetic mutations and response to ab-PCSK9 therapy.

Methods

72 FH patients, 32 women and 40 men (53.91± 13.1 yrs), in primary prevention (N=45) and secondary prevention (N=27), were recruited. This sample included patients with mutations in LDLR gene: heterozygotes for missense mutations (N=31), for null mutations (N=30), compound heterozygotes or homozygotes (N=11). At baseline visit, the whole sample had a maximally tolerated lipid lowering therapy (MT-LLT) without ab-PCSK9; 15 patients had MT-LLTs intolerance. After 160 days with ab-PCSK9 therapy we evaluated the achievement of a goal (LDL-C<70 mg/dL in primary prevention without Diabetes Mellitus, LDL-C<55 mg/dL).

Results

29/72 patients (40.7%) of the whole sample achieved the goal of LDL-C. Of them 14/29 (48.2%) were in primary prevention, 15/29 (51.7%) in secondary prevention, no difference in achievement of the goal. We then evaluated the percent of patients achieving the goal of LDL-C:

16/31 (51.6%) patients with missense mutation and 16/30 (53.3%) patients with null mutation, no significant difference among groups;

0/11 compound heterozygotes or homozygotes;

3/15 (20.0%) MT-LLTs intolerance.

The other main cardiovascular risk factors did not influence of the achievement the goal of LDL-C.

Conclusions

These findings indicate lack of correlation between type of mutation in heterozygous FH patients and ab-PCSK9 therapy response. Response was poorest in patients with compound heterozygosis or homozygosis mutation as compared to heterozygotes. The intolerance to MT-LLT was associated with poor achievement of the goal of LDL-C.