Evolocumab Shows Sustained Cardiovascular Benefits in Older Patients With ASCVD: FOURIER Trial Findings

The findings, published in the Journal of the American College of Cardiology, suggest that early initiation of evolocumab provides significant lipid-lowering effects and cardiovascular protection comparable to those observed in younger patients. Notably, older patients demonstrated a more favorable number needed to treat (NNT) to reduce major cardiovascular events, reinforcing the potential of this therapy in high-risk populations.

Uncertainty regarding the effectiveness and safety of intensive low-density lipoprotein cholesterol (LDL-C) reduction in older patients has led to more conservative recommendations for individuals aged 75 and above in U.S. guidelines. At the same time, ASCVD remains a major cause of morbidity and mortality worldwide, with older adults being particularly vulnerable to adverse outcomes. While lipid-lowering therapies such as statins and ezetimibe are commonly used, PCSK9 inhibitors like evolocumab provide a potent additional option for reducing LDL-C levels. However, limited data exist on the long-term benefits of PCSK9 inhibition in this age group, highlighting the need for further research.

To fill this knowledge gap, Samer Al Said, TIMI Study Group, Cardiovascular Division, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, Massachusetts, USA, and colleagues seek to evaluate the long-term benefits of evolocumab in patients aged 75 and older.

For this purpose, the researchers analyzed data from the FOURIER trial, which enrolled 27,564 patients aged 18 to 85 years with atherosclerotic cardiovascular disease, randomly assigning them to receive either evolocumab or a placebo, with a median follow-up of 2.2 years. In the subsequent open-label extension (FOURIER-OLE), 6,635 participants continued on open-label evolocumab for an additional median follow-up of five years.

The primary endpoint, which included cardiovascular death, myocardial infarction, stroke, hospitalization for unstable angina, or coronary revascularization, was assessed based on the initial allocation to evolocumab or placebo, stratified by age (<75 vs. ≥75 years). While individual components of the composite endpoint were underpowered for analysis, the annualized incidence rates of adverse events were evaluated across age groups during the parent FOURIER trial and the combined FOURIER and FOURIER-OLE studies for those originally assigned to evolocumab.

The study led to the following findings:

• Among 27,564 patients, 2,526 (9%) were aged 75 years or older at the time of enrollment in the FOURIER trial (median age: 77 years).
• The median follow-up duration across FOURIER and FOURIER-OLE was 7.1 years, with a maximum follow-up of 8.7 years.
• Earlier initiation of evolocumab reduced the primary endpoint rate as effectively in older patients (HR: 0.79) as in younger patients (HR: 0.86).
• Absolute risk reduction was 5.4% in older and 2.3% in younger patients, leading to numbers needed to treat 19 and 44, respectively.
• Annualized incidence rates of safety events were generally comparable across treatment arms in both age groups.

The findings suggest that elderly patients with atherosclerotic cardiovascular disease receiving long-term treatment with the PCSK9 inhibitor evolocumab experience clinical benefits comparable to those observed in younger patients.

"Notably, the absolute reduction in the primary composite endpoint—including cardiovascular mortality, myocardial infarction, stroke, hospitalization for unstable angina, and coronary revascularization—was greater in patients aged 75 years and older. This resulted in a lower number needed to treat, highlighting the potential of evolocumab as an effective lipid-lowering therapy for older high-risk individuals," the researchers wrote.

Reference:

Al Said S, O’Donoghue ML, Ran X, et al. Long-term lipid-lowering with evolocumab in older individuals. JACC. 2025;85:504-512.