lipoprotein(a) levels are genetically determined and elevated are risk factors for cardiovascular disease and aortic stenosis .
This was a randomized, double-blind , placebo-controlled, dose-ranging trial in 286 patients with known cardiovascular disease and lipoprotein(a) levels ≥60 mg/dL (150 nmol/L).
Subcutaneous injection of 6-12 months hepatocyte-directed antisense oligonucleotide AKCEA-APO(a)-LRx, termed APO(a)-LRx (20, 40 or 60 mg every 4 weeks; 20 mg every 2 once weekly; or 20 mg once weekly), or saline placebo control. Lipoprotein(a) levels were determined using an isoform-independent analysis method. Primary endpoint: Percent change in lipoprotein(a) levels from baseline to 6 months (monthly at week 25; other methods at week 27).
The baseline median of lipoprotein (a) levels in these 6 groups is 204.5-246.6nmol/L. Subcutaneous injection of APO(a)-LRx caused a dose-dependent decrease in lipoprotein(a) levels, 20 mg once every 4 weeks, an average decrease of 35%; 40 mg once every 4 weeks, an average decrease of 56%; 20 mg once every 2 weeks, an average decrease 58%; 60 mg once every 4 weeks, an average reduction of 72%; 20 mg once a week, an average reduction of 80%; compared with placebo 6%. There were no significant differences in platelet count , liver and kidney function, or influenza-like symptoms at any dose of APO(a)-LRx compared with placebo. The most common adverse event is injection site reaction.
APO(a)-LRx dose-dependently reduces lipoprotein(a) levels in patients with cardiovascular disease and elevated lipoprotein(a). The change in lipoprotein (a) level of
is shown in the figure below. The percentage change of
over time is shown in the figure below. The percentage of lipoprotein (a) level of
falling to ≤50mg/dl is shown in the figure below. The absolute change of
from baseline to 6 months The value changes are shown in the figure below,
N Engl J Med 2020;382:244-55.
