Introduction: Familial hypercholesterolemia (FH) is associated with 10-20 fold increased CHD risk and requires aggressive low density lipoprotein cholesterol (LDL-C) lowering, ideally initiated at a young age. Late diagnosis and inability to achieve LDL-C goals impede care and portend worse outcomes. The FH Foundation CASCADE FH patient registry consists of data from lipid specialty clinics and was analyzed prospectively.
Hypothesis: LDL-C goal achievement improved among FH patients in the registry over time, particularly after availability of anti-PCSK9 drugs beginning mid-2015.
Methods: Out of 3910 FH patients in the registry, 958 with longitudinal data collected between 4/14-2/17 were analyzed for changes in health status and LDL-C (Chi-squared tests for categorical and Kruskal Wallis for continuous variables).
Results: Mean entry age was 57 ± 15 yr; mean follow-up was 12.5 ± 6 months with 1.2 ± 0.5 visits; LDL-C was 256 ± 85 mg/dl untreated (n=676) and 140 ± 65 mg/dl at entry to registry; CHD was present in 41% at entry. LDL-C was lower at last follow-up vs entry (118 ± 69 mg/dl, P<0.0001), with greater goal achievement vs entry (LDL-C < 100 mg/dl: 41.8 vs 29.3%, P<0.0001; LDL-C < 70 mg/dl, 17.6 vs 10.9%, P<0.0001). CHD events were uncommon during the short follow-up (3.8%); mean entry LDL-C with events vs no events was 158 ± 78 vs 140 ± 64 mg/dl (P=0.17); goal achievement at entry was less (LDL-C < 100 mg/dl: 22.2 vs 47.2%, P=0.007; LDL-C < 70 mg/dl, 16.7 vs 36.1%, P=0.03). Among the subgroup of statin non-users (20.3% at entry and 21.9% at follow-up), statin intolerance was reported in 77.3% at entry and 75.2% at follow-up; myalgia was the most common symptom (87.5%). Non-statin LLT use increased from entry to follow up (65.1 to 73.2%) with ezetimibe being most commonly used drug (44.6% at follow-up). Beginning 4/1/16 anti-PCSK9 mAb use was 13.2% at entry and 23.9% after follow-up.
Conclusions: LDL-C goal achievement has improved over time in this FH population followed in lipid specialty clinics, but is still suboptimal. Statin intolerance and lack of access to non-statin medications are barriers that contribute. Strategies for prevention of CHD in this high risk population need to include improved access to non-statin medications to facilitate greater LDL-C lowering.