Abstract 12103: Intraindividual Variability in Serial Lipoprotein(a) Concentration Among Placebo-Treated Patients in the OCEAN(a)-DOSE Trial
Prakriti Gaba, Michelle L. O’Donoghue, J. Antonio G. López, Robert S. Rosenson, Gerald F. Watts, Julia Kuder, KyungAh Im, Helina Kassahun, Huei Wang, You Wu, Jingying Wang, E. Magnus Ohman, Marc S. Sabatine
Abstract
Background: It has been suggested that lipoprotein(a) [Lp(a)] concentrations are stable over time and need to be measured only once in a lifetime. However, data assessing intraindividual variability in Lp(a) concentration are limited. Methods: OCEAN(a)-DOSE, a phase 2, randomized trial of the Lp(a)-lowering siRNA therapy olpasiran, enrolled 281 patients with atherosclerotic cardiovascular disease (ASCVD) and Lp(a) >150 nmol/L. Analyses were conducted in patients randomized to placebo (n=53) with serial Lp(a) values every 4 to 12 weeks through 72 weeks (820 total serum samples). Intra-individual biological variation (CV i ) was calculated as standard deviation of Lp(a) values over time in an individual divided by the mean of those values. All Lp(a) values were measured using the Roche Tina-quant Gen.2 assay reporting in molarity (assay CV 0.7% at 105 nmol/L). Results: Median baseline Lp(a) in the placebo arm was 246 nmol/L (IQR 200-343); median number of Lp(a) measurements per subject was 16. Whereas the overall Lp(a) concentration remained similar across visits (standard deviation 2.6% of the mean), the intra-individual variation over time (CV i ) was 10% [SD 3.9%] of the mean. This variation remained similar across a range of mean Lp(a) values for each participant (Figure). The absolute observed differences in the placebo arm over time across all visits was 22 ± 21 nmol/L (mean ± SD), with a maximum absolute difference of up to 135 nmol/L from an individual patient’s mean. When evaluating outliers, 23% of patients experienced an upward or downward > or equal to 25% change from their individual mean on at least 1 visit, and 51% experienced an upward or downward > or equal to 50 nmol/L change on at least 1 visit. Conclusion: Among patients with ASCVD and elevated baseline Lp(a) concentration, there was notable intra-individual variability in Lp(a) concentration over 72 weeks of follow-up. These findings suggest that Lp(a) may need to be measured more than once in a lifetime.