Abstract 12103: Intraindividual Variability in Serial Lipoprotein(a) Concentration Among Placebo-Treated Patients in the OCEAN(a)-DOSE Trial
Prakriti Gaba, Michelle O'Donoghue, J. A Lopez, Robert S Rosenson, Gerald F Watts, Julia Kuder, KyungAh Im, Helina Kassahun, Huei Wang, You Wu, Jingying Wang, Erik Magnus Ohman, Marc S Sabatine- Physiology (medical)
- Cardiology and Cardiovascular Medicine
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.