TY - JOUR
T1 - Relationship between low-density lipoprotein cholesterol and lipoprotein(A) lowering in response to PCSK9 inhibition with evolocumab
AU - Shapiro, Michael D.
AU - Minnier, Jessica
AU - Tavori, Hagai
AU - Kassahun, Helina
AU - Flower, Andrea
AU - Somaratne, Ransi
AU - Fazio, Sergio
N1 - Publisher Copyright:
© 2019 The Authors and Amgen Inc.
PY - 2019
Y1 - 2019
N2 - 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 years [interquartile range: 51–66 years]). Baseline mean level of LDL-C was 133.6 mg/dL (SE: 1.7) and median Lp(a) level was 46.4 mg/dL (interquartile range: 18.4–82.4 mg/dL). A discordant response was observed in 165 (19.7%) patients. With these cutoffs, the prevalence of discordance was higher when considering baseline Lp(a) concentrations >30 mg/dL (26.5%) or >50 mg/ dL (28.6%). Conclusions—We demonstrate high prevalence of discordance in LDL-C and Lp(a) reduction in response to evolocumab, particularly when considering higher baseline Lp(a) concentrations, indicating the possibility of alternative pathways beyond LDLR (LDL receptor)–mediated clearance involved in Lp(a) reduction by evolocumab.
AB - 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 years [interquartile range: 51–66 years]). Baseline mean level of LDL-C was 133.6 mg/dL (SE: 1.7) and median Lp(a) level was 46.4 mg/dL (interquartile range: 18.4–82.4 mg/dL). A discordant response was observed in 165 (19.7%) patients. With these cutoffs, the prevalence of discordance was higher when considering baseline Lp(a) concentrations >30 mg/dL (26.5%) or >50 mg/ dL (28.6%). Conclusions—We demonstrate high prevalence of discordance in LDL-C and Lp(a) reduction in response to evolocumab, particularly when considering higher baseline Lp(a) concentrations, indicating the possibility of alternative pathways beyond LDLR (LDL receptor)–mediated clearance involved in Lp(a) reduction by evolocumab.
KW - Lipid-lowering therapy
KW - Lipoprotein[a]
KW - Low-density lipoprotein cholesterol
KW - Proprotein convertase subtilisin/kexin type 9
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U2 - 10.1161/JAHA.118.010932
DO - 10.1161/JAHA.118.010932
M3 - Article
C2 - 30755061
AN - SCOPUS:85061498125
SN - 2047-9980
VL - 8
JO - Journal of the American Heart Association
JF - Journal of the American Heart Association
IS - 4
M1 - e010932
ER -