Clinical Features and Gaps in the Management of Familial Hypercholesterolemia with Prevalent Cardiovascular Disease

Background:
Familial hypercholesterolemia (FH) is associated with premature atherosclerotic cardiovascular disease (ASCVD). The introduction of potent new therapeutic agents for treating FH underlies the importance of improved clinical diagnosis and more precise identification of treatment gaps.

Methods:
Regional database of patiens with high clinical probability of FH (1,690 adults <75 years), was examined to explore clinical manifestations and current needs in the management of FH patients with prevalent ASCVD. Arterial teritories involved, coronary revascularizations performed, lipid-lowering therapies provided and treatment gaps were evaluated.

Results:
ASCVD was present in 246(15%) FH patients with median age at diagnosis of 50 years (IQR 40-57), of whom 83% had coronary artery disease (CAD), 19% stroke and 13% peripheral artery disease. Median peak low-density lipoprotein cholesterol (LDL-C) was 273 mg/dl (IQR 257-310). Most patients (70%) had additional risk factors: diabetes (29%), hypertension (55%) and smoking (27%). Coronary revascularization was required in 90% of the CAD patients (35% performing bypass surgery) and one-third had recurrent procedures. Peak LDL-C >300mg/dl was associated with both repeat procedures and need for bypass surgery. Despite high-intensity statin, prescribed in 82% and combined with ezetimibe in 42%, LDL-C reduction ≥50% was achieved in 55% of patients, LDL-C <100mg/dl in 27% and only 5% reached LDL-C <70mg/dl. Lipid-lowering prescriptions were not filled in the last 6 months by 20% of patients. Treatment intensity and drug adherence were directly associated with attainment of LDL-C goals.

Conclusions:
FH patients developed CAD at an early age with a high rate of multivessel disease and need for recurrent coronary interventions. In spite of intensive therapy with lipid-lowering agents, attainment of LDL-C treatment goals was considerably low. Enhancing patients adherence, combination therapy with ezetimibe, as well as the introduction of PCSK9 inhibitors, may raise the likelihood of attaining LDL-C treatment goals, aiming to successfully reduce cardiovascular events.