Cardiovascular outcomes in patients with coronary artery disease and elevated lipoprotein(a): Implications for the OCEAN(a)-Outcomes trial population

Abstract

Abstract Background Lipoprotein(a) [Lp(a)] is associated with atherosclerotic cardiovascular (CV) disease. The ongoing Olpasiran Trials of Cardiovascular Events and Lipoprotein(a) Reduction [OCEAN(a)]-Outcomes trial is evaluating whether Lp(a) lowering can reduce the incidence of CV events among patients with prior myocardial infarction (MI) or percutaneous coronary intervention (PCI) and elevated Lp(a) (≥ 200 nmol/L). Purpose To evaluate the association of elevated Lp(a) with CV outcomes in an observational cohort resembling the OCEAN(a)-Outcomes trial main enrollment criteria. Methods This retrospective study leveraged a large Lp(a) registry derived from electronic health records at two large academic medical centers in the US. The registry included patients aged 18-85 years with Lp(a) measured as part of their clinical care between 2000 and 2019. While patients were required to have a history of MI, or PCI, those with severe kidney dysfunction or a malignant neoplasm were excluded. Elevated Lp(a) was defined as ≥ 200 nmol/L consistent with the OCEAN(a) -Outcomes trial. The primary outcome was a composite of coronary heart disease (CHD) death, MI, or coronary revascularization. A combination of natural language processing algorithms, billing and ICD codes, laboratory data, and the National Death Index were employed to identify outcomes and covariates. Results Among the 16,821 patients in the registry, 3,142 (18.7%) met the established inclusion and exclusion criteria. Among eligible patients, the median age was 61 (IQR: 52-73) years, 28.6% were women, and 12.3% had elevated Lp(a). Patients with elevated Lp(a), versus non-elevated Lp(a), were more likely to be women (37.6% vs. 27.3%, p<0.001) and to have hyperlipidemia (90.2% vs. 86.0%, p=0.024). Over a median follow-up of 12.2 years (IQR: 6.2-14.3), the primary composite outcome occurred more frequently in patients with versus without elevated Lp(a) (46.0% vs. 38.0%, HR=1.30 [95%CI: 1.09-1.53], p=0.003; Figure 1). Following adjustment for measured confounders, elevated Lp(a) remained independently associated with the primary outcome (adjHR=1.33 [95%CI: 1.12-1.58], p=0.001). Elevated Lp(a) was also associated with increased risk for most secondary outcomes (Table 1). Conclusions In an observational cohort resembling the main OCEAN(a)-Outcomes Trial enrollment criteria, patients with an Lp(a) ≥ 200 nmol/L had a higher risk of CV outcomes.