Cognition After Lowering LDL-Cholesterol With Evolocumab.
Level 2 - randomized trial
Secondary analysis of a large randomized, double-blind, placebo-controlled trial
PubMed 32381158 · doi:10.1016/j.jacc.2020.03.039
What was done
In the randomized, double-blind, placebo-controlled FOURIER trial, patients with atherosclerotic cardiovascular disease and elevated atherogenic cholesterol on background statin therapy were assigned to evolocumab or placebo. At the final study visit (median duration 2.2 years), participants completed a 23-item survey derived from the Everyday Cognition (ECog) scale covering memory and executive domains, comparing current everyday function with baseline (scored 1 for no change/improvement to 4 for consistently much worse). Patient-reported cognitive decline (ECog score ≥2) was compared by randomized treatment arm and by achieved LDL-C at 4 weeks.
What was found
Among 22,655 patients who completed the survey, cognitive decline rates were similar between placebo and evolocumab: - Total ECog decline: 3.6% for placebo vs. 3.7% for evolocumab (p = 0.62) - Memory subdomain decline: 5.8% vs. 6.0% - Executive subdomain decline: 3.6% vs. 3.7% Similarly, cognitive decline did not differ significantly between the 2,338 patients achieving LDL-C <20 mg/dL and the 3,613 patients with LDL-C ≥100 mg/dL (3.8% vs. 4.5%, p = 0.57).
Why it matters
These findings provide robust reassurance across a broad trial cohort that PCSK9 inhibition and profound LDL-C lowering do not adversely affect patient-reported cognitive function over a 2-year period.
Limits
Cognition was assessed solely through retrospective patient self-report at the final study visit rather than standardized, objective neurocognitive testing in the overall cohort. Follow-up was relatively short (median 2.2 years) to detect insidious or long-term neurodegenerative outcomes. The population was restricted to individuals with high-risk cardiovascular disease receiving statins.
Cited by
- supports The FOURIER clinical trial demonstrated that reducing LDL cholesterol down into the 20s mg/dL appeared to be safe.