Evolocumab would be the best next step. Post hoc analyses from three randomized controlled trials involving PCSK9 inhibitors (PCSK9is)—FOURIER (Further Cardiovascular Outcomes Research With PCSK9 Inhibition in Subjects With Elevated Risk), ODYSSEY OUTCOMES (Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab), and VESALIUS-CV (Effect of Evolocumab in Patients at High Cardiovascular Risk Without Prior Myocardial Infarction or Stroke)—have demonstrated greater absolute risk reduction with PCSK9is for those with higher Lp(a) levels, especially for coronary heart disease outcomes (Table 1). More broadly, the results of these three trials have demonstrated that the addition of PCSK9is among individuals with clinical ASCVD and LDL-C levels ≥70 mg/dL (FOURIER and ODYSSEY OUTCOMES) or without clinical ASCVD and LDL-C levels ≥90 mg/dL (VESALIUS-CV) reduces the risk of major adverse CV events. The median LDL-C level achieved in the treatment arm across these trials was between 30 and 53 mg/dL.

Table 1: Select Findings From Post Hoc Analyses of Three RCTs Involving PCSK9is: FOURIER, ODYSSEY OUTCOMES, and VESALIUS-CV

^a The largest differences between Lp(a) groups were observed when observing the outcome of MI alone (NNT 108 vs. 28).
CHD = coronary heart disease; FOURIER = Further Cardiovascular Outcomes Research With PCSK9 Inhibition in Subjects With Elevated Risk; MI = myocardial infarction; NNT = number needed to treat; ODYSSEY- OUTCOMES = Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab; PCSK9i = PCSK9 inhibitor; RCT = randomized controlled trial; UA = unstable angina; VESALIUS-CV = Effect of Evolocumab in Patients at High Cardiovascular Risk Without Prior Myocardial Infarction or Stroke.

As such, there is a Class 1 recommendation to add PCSK9is to achieve treatment goals and reduce ASCVD risk among individuals with clinical ASCVD and elevated Lp(a) levels who have not achieved LDL-C and non–HDL-C goals with maximally tolerated statin therapy.

Although TG levels were elevated in this patient and addition of icosapent ethyl might be reasonable, this is a Class 2b recommendation in adults ≥50 years of age who are taking statins and have clinical ASCVD or diabetes mellitus and one or more ASCVD risk factors with persistently elevated TG levels of 150-499 mg/dL and LDL-C levels of <100 mg/dL.

This patient case quiz is part of the larger Implementing the 2026 Dyslipidemia Guidelines: From Risk Stratification to Personalized Treatment initiative, supported by Merck & Co. and Eli Lilly and Company. To visit the Learn Prevention grant page and access additional educational activities on this topic, click here.

References

1. Blumenthal RS, Morris PB, Gaudino M, et al. 2026 ACC/AHA/AACVPR/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA guideline on the management of dyslipidemia: a report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. J Am Coll Cardiol. 2026;87(19):2624-2757. doi:10.1016/j.jacc.2025.11.016
2. O'Donoghue ML, Fazio S, Giugliano RP, et al. Lipoprotein(a), PCSK9 inhibition, and cardiovascular risk. Circulation. 2019;139(12):1483-1492. doi:10.1161/CIRCULATIONAHA.118.037184
3. Bittner VA, Szarek M, Aylward PE, et al. Effect of alirocumab on lipoprotein(a) and cardiovascular risk after acute coronary syndrome. J Am Coll Cardiol. 2020;75(2):133-144. doi:10.1016/j.jacc.2019.10.057
4. Monguillon V, Marston NA, Bohula EA, et al. Lipoprotein(a) levels, risk of cardiovascular events, and benefit of evolocumab: findings from the VESALIUS-CV trial. Circulation. 2026;153(25):1960-1968. doi:10.1161/CIRCULATIONAHA.126.080999