ESC Congress 2026 Abstract · Oct 26, 2026
Lipoprotein(a) variability in high CV risk patients with hypertriglyceridemia and controlled LDL-C on statin therapy – REDUCE-IT Lp(a) Variability
By Szarek M, Bhatt DL, Miller M et al.
Introduction: Therapeutics that dramatically lower lipoprotein(a) (Lp(a)) currently in phase 3 testing have enrolled participants with concentrations above certain thresholds, e.g., ≥70 mg/dL or ≥150 nmol/L. Although repeated testing of Lp(a) is generally viewed as unnecessary due to the fact that concentrations are primarily genetically determined, there are limited data on whether there are characteristics associated with greater variability in Lp(a) measurements over time, which might impact eligibility for these treatments and therefore justify repeated testing. Purpose: To document predictors of variability in Lp(a) assessments in a cohort of individuals with elevated triglyceride levels and well-controlled LDL-C who were receiving statin therapy. Methods: The analysis cohort comprised participants from the REDUCE-IT trial with measurements of Lp(a) mass concentration at randomisation, month 12, and month 24. Variability in assessments was summarized by a plot of per-participant average versus the range of the three assessments. The range was related to participant characteristics in linear regression models, overall, and for subsets above the LLQ, and with averages above clinically relevant thresholds. Results: Among 8179 participants, 5036 (61.6%) had baseline, month 12, and month 24 Lp(a) assessments; median (IQR) Lp(a) concentrations were 11.4 (4.9, 36.7), 12.4 (5.2, 39.2), and 12.5 (5.1, 38.9) mg/dL, respectively. Although the assessments were strongly correlated (all pairwise Spearman r>0.93), variability increased with average concentration (Figure). A total of 5.5% of 416 participants with baseline Lp(a) 30 to <50 mg/dL had at least one subsequent assessment ≥70 mg/dL, whereas 3.2% of 630 participants with baseline Lp(a) ≥70 mg/dL had at least one subsequent assessment <50 mg/dL. While the majority of characteristics were significantly related to range, only baseline and average Lp(a) explained a meaningful proportion of the variance in this outcome (Table). Conclusion: In REDUCE-IT, over 24 months, subsets of individuals unselected for Lp(a) shifted in and out of ranges studied in outcomes studies of Lp(a)-targeting treatments. Baseline and average concentration explained a meaningful proportion of variability, suggesting repeated testing of those with relatively high Lp(a) may be warranted to determine eligibility for treatment if these therapeutics are indicated only for individuals with relatively high levels.Figure and Table