Cognition of patients with stable atherosclerotic cardiovascular disease on a maximally tolerated statin regimen was not affected by the addition of evolocumab, according to study results published in the Journal of the American College of Cardiology.

This was a subanalysis of the randomized, double-blind, placebo-controlled Further Cardiovascular Outcomes Research With PCSK9 Inhibitors in Subjects With Elevated Risk (FOURIER; Identifier: NCT01764633) trial. In this study, participants were randomly assigned to receive subcutaneous evolocumab 140 mg biweekly or 420 mg monthly (n=11,363; mean age, 62.5±9.0 years; 75.9% men; 85.2% white) or placebo (n=11,292; mean age, 62.5±8.9 years; 76.0% men; 85.0% white). After a median of 2.2 years, participants (n=22,655) of the FOURIER study were asked to complete the 23-item Everyday Cognition scale (ECog; study’s primary outcome), which evaluates memory and executive function. Everyday function at the end vs the beginning of the trial was scored as follows: 1: no change or improvement; 2: occasionally worse; 3: consistently little worse; and 4: consistently much worse.

At the end of follow-up, cognitive decline (ie, ECog ≥2) was reported by 3.7% of patients receiving evolocumab vs 3.6% in the placebo group (P =.62). Scores for the memory and executive function (3.7% vs 3.6%; P = .83) subdomains were comparable in the evolocumab and placebo groups (memory: 6.0% vs 5.8%, respectively; P =.53; executive function: 3.7% vs 3.6%, respectively; P =.83).

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The percentage of patients reporting cognitive decline was comparable in those who had reached very low LDL-C levels (n=2338) vs those who had LDL-C levels ≥100 mg/dL (n=3613) (3.8% vs 4.5%, respectively; P =.57).

Study limitations include a relatively short follow-up duration, assessment of ECog score at a single time point, lack of ECog completion by 18% of participants, and the fact that ECog does not exhaustively evaluate all aspects of cognition.

“These data confirm the neurocognitive safety of intensive LDL-C reduction with evolocumab while reducing recurrent CV events in high-risk patients, and suggest that very low achieved LDL-C levels may be safely targeted for high-risk patients,” noted the authors.

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The study was sponsored by Amgen.


Gencer B, Mach F, Guo J, et al. Cognition after lowering LDL-cholesterol with evolocumab. J Am Coll Cardiol. 2020;75(18):2283-2293. doi:10.1016/j.jacc.2020.03.039