23 May Study Finds No Link Between Repatha® (evolocumab) and Cognitive Decline
MedicalResearch.com Interview with:
Robert P. Giugliano, MD, SM
Senior Investigator, TIMI Study Group
Brigham and Women’s Hospital
Professor of Medicine
Harvard Medical School Boston, MA
MedicalResearch.com: What is the background for this study?
Response: Some prior studies had suggested that lipid lowering therapies were associated with impaired cognition. We sought to explore this question in a prospectively designed substudy of the large FOURIER randomized, double-blind clinical trial utilizing patient self-surveys administered the end of the study to determine whether patients themselves noticed any changes in cognition over the duration of the trial.
The survey tool was a shortened version of the Everyday Cognition Questionnaire (see attached) that asks patients 23 questions that assess memory and executive function (including subdomains of planning, organization, and divided attention). The questions are in the format of “Compared to the beginning of the study, has there been any change in …..”, and are graded as 1=better/no change, 2=questionable/occasionally worse, 3=consistently a little worse, 4=consistently much worse.
MedicalResearch.com: What are the main findings?
Response: We found no differences between the PCSK9 inhibitor evolocumab and placebo in the frequency of patients who reported worsening of any of the categories of cognition among 22,655 patients who were followed for an average of 2.2 years. There were also no differences between the rates by treatment in high risk subgroups, such as patients age 75 or older, those with pre-existing cerebrovascular disease, or those with a history of neurologic disease other than stroke. Furthermore, we did not see worsening cognition with progressively lower levels of achieved LDL-C, including among the 2338 patients who achieved a very low LDL-C concentration of <20 mg/dL at 4 weeks.
MedicalResearch.com: What should readers take away from your report?
Response: These findings are important as they add to the growing body of evidence demonstrating the lack of effect on cognition in patients who are treated with a PCSK9 inhibitors and in patients who achieve very low LDL-C levels (prior reports showed no differences in cognitive adverse events or in formal serial testing of cognition using CANTAB testing).
The novelty here is that these are patient reports of what they experienced based on a self-survey. The implications for clinical practice are that health care providers and patients should be reassured that PCSK9 inhibitors and achievement of very low LDL-C levels do not appear to cause cognitive decline.
The major limitation of these data is that the average duration of follow-up was 2.2 years, although other studies with other cholesterol-lowering agents did not show adverse effects on cognition out to 6 years (even among those achieving an LDL-C <30 mg/dL), and that additional longer-term data are forthcoming with PCSK9 inhibitors.
Disclosures: The FOURIER trial was sponsored by a research grant from Amgen, who also markets evolocumab. Please see the JACC website and the manuscript from author disclosures.
Gencer B, Mach F, Murphy SA, et al. Efficacy of Evolocumab on Cardiovascular Outcomes in Patients With Recent Myocardial Infarction: A Prespecified Secondary Analysis From the FOURIER Trial. JAMA Cardiol. Published online May 20, 2020. doi:10.1001/jamacardio.2020.0882
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