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

Arthur Shiyovich; Adam N Berman; Stephanie A Besser; David W Biery; Daniel M Huck; Brittany Weber; Christopher Cannon; James L Januzzi; John N Booth 3rd; Khurram Nasir; Marcelo F Di Carli; J Antonio G López; Shia T Kent; Deepak L Bhatt; Ron Blankstein

doi:10.1093/ehjopen/oead077

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

Eur Heart J Open. 2023 Aug 27;3(4):oead077. doi: 10.1093/ehjopen/oead077. eCollection 2023 Jul.

Authors

Arthur Shiyovich¹, Adam N Berman¹, Stephanie A Besser¹, David W Biery¹, Daniel M Huck^{1

2}, Brittany Weber¹, Christopher Cannon¹, James L Januzzi³, John N Booth 3rd⁴, Khurram Nasir⁵, Marcelo F Di Carli^{1

2}, J Antonio G López⁶, Shia T Kent⁴, Deepak L Bhatt^{1

7}, Ron Blankstein^{1

2}

Affiliations

¹ Division of Cardiovascular Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
² Department of Radiology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
³ Cardiology Division, Massachusetts General Hospital, Harvard Medical School, and Baim Institute for Clinical Research, Boston, MA 02115, USA.
⁴ Center for Observational Research, Amgen Inc., Thousand Oaks, CA 91320, USA.
⁵ Department of Cardiovascular Medicine, Division of Cardiovascular Prevention and Wellness, Houston Methodist DeBakey Heart and Vascular Center, Houston, TX 77030, USA.
⁶ Global Development, Amgen Inc., Thousand Oaks, CA 91320, USA.
⁷ Mount Sinai Heart, Icahn School of Medicine at Mount Sinai Health System, New York, NY 10029, USA.

Abstract

Aims: 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 cardiovascular events among patients with prior myocardial infarction (MI) or percutaneous coronary intervention (PCI) and elevated Lp(a) (≥200 nmol/L). The purpose of this study is to evaluate the association of elevated Lp(a) with cardiovascular outcomes in an observational cohort resembling the OCEAN(a)-Outcomes trial main enrolment criteria.

Methods and results: This study 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 death, MI, or coronary revascularization. Natural language processing algorithms, billing and ICD codes, and laboratory data were employed to identify outcomes and covariates. A total of 3142 patients met the eligibility criteria, the median age was 61 (IQR: 52-73) years, 28.6% were women, and 12.3% had elevated Lp(a). 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%, unadjHR = 1.30 (95% CI: 1.09-1.53), P = 0.003]. 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].

Conclusion: In an observational cohort resembling the main OCEAN(a)-Outcomes Trial enrolment criteria, patients with an Lp(a) ≥200 nmol/L had a higher risk of cardiovascular outcomes.

Keywords: Cardiovascular outcomes; Coronary artery disease; Lipoprotein(a); Olpasiran.