Bridging the gap: real-world eligibility for lipoprotein(a)-targeted therapies in chronic and acute coronary syndrome

Background

Lipoprotein(a) [Lp(a)] is an established causal risk factor for the development and progression of atherosclerotic cardiovascular disease (ASCVD). Multiple phase 3 trials are currently evaluating targeted Lp(a)-lowering therapies using high entry thresholds. However, real-world eligibility in secondary prevention remains limited, and no universally accepted cut-offs exist. The 2025 European Society of Cardiology (ESC) and European Atherosclerosis Society (EAS) guidelines recommend considering Lp(a) ≥105 nmol/L as a cardiovascular risk-enhancing factor. [1]

Purpose

To evaluate real-world eligibility for emerging Lp(a)-lowering therapies and apheresis in patients with chronic coronary syndrome (CCS) and acute coronary syndrome (ACS), and to determine the association between Lp(a) levels and 5-year cardiovascular outcomes.

Methods

Consecutive patients undergoing percutaneous coronary intervention (PCI) at a tertiary care centre between 2010 and 2021 with Lp(a) measured in nmol/L were analysed. Eligibility was assessed according to trial-aligned thresholds (≥150, ≥175, ≥200 nmol/L) and the guideline-recommended risk-enhancing cut-off (≥105 nmol/L). Lp(a) apheresis eligibility was evaluated using national Central European criteria (Austria: Lp(a) >250 nmol/L plus prior revascularization; Germany: Lp(a) >120 nmol/L plus prior revascularization and LDL cholesterol <130 mg/dL). Five-year major adverse cardiovascular events (MACE) and target lesion failure (TLF) were endpoints.

Results

Among 5,942 PCI patients, median Lp(a) was 26.0 [IQR 9.0 – 106.0] nmol/L and 1,498 (25.2%) patients had Lp(a) levels ≥105 nmol/L. Eligibility decreased at higher trial-aligned thresholds: 1,094 (18.4%) ≥150 nmol/L, 881 (14.8%) ≥175 nmol/L, and 688 (11.6%) ≥200 nmol/L (Figure 1). Lp(a) levels were similar in chronic coronary syndrome (CCS; median 28.0 [IQR 9.0 – 118.5] nmol/L) and acute coronary syndrome (ACS; median 25.0 [IQR 9.0 – 96.5] nmol/L), with modestly higher values in CCS. National apheresis criteria were fulfilled by 1.8% (Austria) and 6.1% (German) of patients.

Over five years, higher Lp(a) was independently associated with an increased risk of MACE (adjusted HR per 1 SD 1.07 [95% CI 1.02 – 1.12]; p = 0.008) and TLF (adjusted HR per 1 SD 1.06 [95% CI 1.01 – 1.11]; p = 0.020), with pronounced associations observed in ACS.

Conclusion

Elevated Lp(a) is highly prevalent in PCI patients and independently associated with adverse 5-year outcomes. While a substantial proportion of patients met thresholds for emerging Lp(a)-lowering therapies, few fulfilled composite apheresis criteria. Systematic Lp(a) testing after PCI may improve risk stratification, identify candidates for emerging therapies, and guide implementation of targeted secondary prevention strategies in routine cardiovascular practice.Figure 1