Written by Babatunde Carew
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Long-term treatment with evolocumab in patients ≥75 with atherosclerotic cardiovascular disease (ASCVD) significantly reduces cardiovascular events and is well tolerated.
Evolocumab – proof that lowering LDL never gets old
People aged 70-100 with elevated LDL have the highest risk of MI and ASCVD. The FOURIER and FOURIER-OLE studies showed that evolocumab combined with statin therapy significantly reduced CV risk in adults. This study assessed the long-term benefits and safety of evolocumab in patients ≥75 with ASCVD using FOURIER and FOURIER-OLE data.
This trial compares both trial groups as a retrospective cohort grouped by age of initiation of evolocumab. As a result, this study has some selection bias, with multiple statistically significant differences in patient characteristics including % male, incidence of stroke, peripheral artery disease, hypertension, prior myocardial infarction, lipid levels, and medication usage (statin intensity, ezetimibe use, aspirin, beta blockers, and RAAS inhibitor). Over a median follow-up of 7 years, evolocumab reduced the composite cardiovascular endpoint (HR 0.79, 95%CI 0.64-0.97) with an absolute risk reduction of 5.4% in patients who were older than 75 at the time of medication initiation with a number needed to treat (NNT=19) compared to younger patients. On secondary analysis, stroke reduction in ≥75 year olds was the only statistically significant reduction (HR 0.54, 95%CI 0.35-0.84, p < 0.021). Evolocumab was well tolerated across age groups. A significant limitation is the lack of a long-term placebo comparison, as all patients in the FOURIER-OLE were treated with evolocumab, and there were statistically significant differences in the patient characteristics when outcomes were compared by the age of initiation.
How does this change my practice?
In elderly patients with known ASCVD, I target an LDL <70 but tend not to push, fearing diminishing returns and polypharmacy. This study shows that intensive lipid lowering with evolocumab added to statin showed no significant safety concerns in patients over a 7-year period and suggests that the effects of evolocumab may be greatest in patients ≥75. This causes me to consider PCSK9i more often in this population, but at around $600 on GoodRx, cost remains a barrier.
Source
Long-Term Lipid Lowering With Evolocumab in Older Individuals. J Am Coll Cardiol. 2025 Feb 11;85(5):504-512. doi: 10.1016/j.jacc.2024.11.019. PMID: 39909681
