Relationship Between Low‐Density Lipoprotein Cholesterol and Lipoprotein(a) Lowering in Response to PCSK9 Inhibition With Evolocumab

2019 
Background Beyond their potent LDL (low‐density lipoprotein) cholesterol (LDL‐C)–lowering efficacy (50–60%), PCSK9 (proprotein convertase subtilisin/kexin type 9) inhibitors also reduce Lp(a) (lipoprotein[a]) levels by 25% to 30%, suggesting a 2:1 response ratio. We aimed to characterize the relationship between LDL‐C and Lp(a) lowering by evolocumab, a PCSK9 inhibitor, in a large clinical trial population and to determine the prevalence of concordant/discordant LDL‐C and Lp(a) responses to PCSK9 inhibition. Methods and Results Data were analyzed from 4 randomized, 12‐week, multicenter, phase 3 evolocumab trials. Patients with familial hypercholesterolemia, nonfamilial hypercholesterolemia, or statin intolerance participated in the trials. The main measure was the degree of concordance or discordance of LDL‐C and Lp(a) in response to PCSK9 inhibition; concordant response was defined as LDL‐C reduction >35% and Lp(a) reduction >10%. The study cohort comprised 895 patients (438 female; median age: 59.0 year...
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