A 50-year-old man with a 10-year history of type 2 diabetes mellitus (T2DM; hemoglobin A1c concentration 8%) presents for cardiovascular (CV) risk management. His medical history is significant for myocardial infarction (MI) 1 year ago treated with PCI and stent placement in the right coronary artery, hypertension, and obesity. His current medications are metformin 500 mg BID, tirzepatide 12.5 mg once weekly, rosuvastatin 40 mg QD, ezetimibe 10 mg QD, lisinopril 20 mg QD, and aspirin 81 mg QD.
His laboratory study results include total cholesterol level 185 mg/dL, LDL-C level 61 mg/dL, HDL-C level 45 mg/dL, triglyceride (TG) level 140 mg/dL, and non–HDL-C level 140 mg/dL.
The correct answer is: C. Add a PCSK9 monoclonal antibody inhibitor to his lipid-lowering therapy.
According to the 2026 ACC/AHA/Multisociety Guideline on the Management of Dyslipidemia, treatment goals should be tailored to a patient's baseline CV risk. This patient met the criteria for very-high-risk secondary prevention given his history of MI (one major ASCVD event), prior coronary stent placement, T2DM, and hypertension, representing multiple high-risk conditions.
For patients in this risk category, the recommended lipid targets are LDL-C level <55 mg/dL and non–HDL-C level <85 mg/dL. Although this patient was already receiving optimal oral lipid-lowering therapy with a high-intensity statin and ezetimibe, additional LDL-C level reduction was required to achieve these goals and further reduce residual CV risk.
Therefore, the best next therapeutic step would be the addition of a PCSK9 monoclonal antibody. This recommendation is supported by robust evidence from the FOURIER (Further Cardiovascular Outcomes Research With PCSK9 Inhibition in Subjects With Elevated Risk) trial with evolocumab and the ODYSSEY OUTCOMES (Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab) trial with alirocumab, both of whose findings demonstrated substantial additional LDL-C level lowering and significant reductions in major adverse CV events among patients at high risk who are already taking statin therapy. Adding a PCSK9 inhibitor offers the greatest likelihood of achieving recommended lipid targets while providing incremental CV risk reduction.
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
- 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
- Sabatine MS, Giugliano RP, Keech AC, et al. Evolocumab and clinical outcomes in patients with cardiovascular disease. N Engl J Med. 2017;376(18):1713-1722. doi:10.1056/NEJMoa1615664
- Schwartz GG, Steg PG, Szarek M, et al. Alirocumab and cardiovascular outcomes after acute coronary syndrome. N Engl J Med. 2018;379(22):2097-2107. doi:10.1056/NEJMoa1801174
