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EBBINGHAUS: Evolocumab does not affect cognitive outcomes

WASHINGTON — The addition of evolocumab to statin therapy did not result in memory loss or other cognitive issues, according to results of the EBBINGHAUS study.

The investigators of FOURIER, which compared evolocumab (Repatha, Amgen) vs. placebo for clinical outcomes in patients with atherosclerotic CVD and elevated LDL on background statin therapy, undertook a cognitive substudy because small studies and case series had raised concerns that statins negatively impact cognitive outcomes, later disproven by larger studies, Robert P. Giugliano, MD, SM, cardiovascular medicine specialist at Brigham and Women’s Hospital and a senior investigator at the Thrombolysis in Myocardial Infarction Study Group, said during a presentation at the American College of Cardiology Scientific Session.

“We designed the EBBINGHAUS study ... to assess the following hypothesis: [Did] the addition of evolocumab to statin therapy in patients with clinically evident [CVD] affect cognitive outcomes? We hypothesized that it would not,” Giugliano said.

Robert Giugliano
Robert P. Giugliano

To determine whether that was true, the researchers enrolled 1,974 patients from FOURIER (mean age, 63 years; 72% men) without dementia or cognitive impairment at baseline, of whom 1,204 who had baseline cognitive testing performed and at least one follow-up cognitive test were included in the primary analysis.

All patients performed Cambridge Neuropsychological Test Automated Battery Assessments at baseline, 6 months, 12 months, 24 months, 48 months and at the end of the study.

Steven E. Nissen, MD

Steven E. Nissen

  • There has been a concern looming for a long time, both for statins and PCSK9 inhibitors, that cholesterol is necessary to the functioning of brain cells, so people who are treated to very low levels of LDL should be tested for cognitive dysfunction. It’s appropriate that the FDA expressed concerns about this to the companies making the PCSK9 inhibitors. They responded with the EBBINGHAUS trial, a large neurocognitive study. I was impressed that it was very rigorous. Interestingly enough, despite the concerns over the years and maybe some signals along the way, there is really no evidence of adverse cognitive effects. It appears that the brain is not adversely affected by treatment to very low LDL levels. That’s important because when we consider the GLAGOV and FOURIER study results, we now have some incentives to treat people to very low LDL, and we need to know if there will be brain-related issues, and now we don’t see any evidence that there is.

    If there is an effect and it’s not seen in a trial of this size, it would have to be very, very rare. The study is pretty conclusive.

    • Steven E. Nissen, MD, MACC
    • Cardiology Today Editorial Board Member
      Cleveland Clinic
  • Disclosures: Nissen reports serving as an investigator on trials sponsored by Amgen, but does not accept honoraria or reimbursement from industry.

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