Dr Robert P. Giugliano on the Results of the EBBINGHAUS Evolocumab Cognitive Study
Past study results had raised concerns about the effect of lipid-lowering drugs like evolocumab on cognitive function, but the EBBINGHAUS trial presented at the American College of Cardiology 66th Scientific Session may finally help put those fears to rest, explained lead study author Robert P. Giugliano, MD, MSc, associate professor of medicine at Harvard Medical School.
Transcript (slightly modified) Can you describe the EBBINGHAUS study and its results?
EBBINGHAUS was a trial of nearly 2000 patients, looking at various assessments of cognition, so memory and working memory and other kind of, orientation, planning, organization, things like that. We were interested in finding out whether this new drug, evolocumab, affects these cognitive parameters or not. There had been older data that suggested either statins or having a very low LDL was associated with impaired cognition. So EBBINGHAUS was a formal study designed to look at cognition of evolocumab, a PCSK9 inhibitor, compared with placebo.
There were, as I mentioned, just under 2000 patients randomized. They underwent a battery of cognitive tests and we also had them fill out questionnaires at the end of the study, which lasted almost 2 years, and tell us what they felt about their memory, organization, planning skills, et cetera, compared to the beginning of the trial. And then the third part of it is we looked at physician-reported cognitive adverse events to see if physicians picked up that there were problems with memory, orientation, planning, et cetera.
There were no differences between evolocumab, the drug, and placebo in any of these measures. Furthermore, we also did an exploratory analysis where we looked at patients according to their achieved LDL. In this trial we got the LDLs down very, very low; on average 30 mg/dL, but we looked at a group who were below 25, 25 to 40, 40 and above, and there were no differences according to the achieved LDL in their cognitive function or between the 2 treatments.
What are the implications of these results for evolocumab’s approval for a broader patient population?
Some clinicians and even the FDA had raised concerns about possible effects on cognition of lipid-lowering drugs, particularly statins, and some earlier data with the PCSK9 inhibitors suggested there may be an association of use of these drugs with impaired cognition. I think what the clinician should take home from this study is that in a dedicated, prospective trial looking at cognition in a variety of different ways, there’s no effect of the drug compared to placebo, even when you looked at the patients who achieved very low LDLs. So I think this information’s reassuring for the clinicians, that they can use these drugs safely without patients having impaired cognition or problems with memory, things like that.