Two-year follow up of FOURIER study in 22,655 patients confirms neurocognitive safety of very low LDL-C levels using a patient self-survey tool.
Heart disease patients taking evolocumab in addition to a statin to achieve extremely low levels of cholesterol do not show increased incidence of neurocognitive impairments, including memory loss or reduction in executive functions (mental skills), while at the same time have a decrease in recurrent cardiovascular events such as stroke and heart attack, according to a study in the Journal of the American College of Cardiology that examined the cognitive function of the entire FOURIER cohort at two years.
Statins are used to reduce low-density lipoprotein cholesterol (LDL-C), or bad cholesterol, and prevent heart disease and stroke. However, some high-risk patients need to take PCSK9 inhibitors combined with a maximally tolerated statin or other lipid-lowering therapies to reduce their LDL-C even more. While prior research has shown heart disease patients do not experience adverse neurocognitive effects when taking PCSK9 inhibitors with statin to treat bad cholesterol, until now there has not been a large-scale trial to investigate the impact of using evolocumab and statin to achieve very low LDL-C levels on patient-reported cognition.
Researchers in this study looked at the self-reported Everyday Cognition study results from 22,655 patients in the original FOURIER trial, which was completed after a median duration of 2.2 years. The percentage of patients who reported cognitive decline at the end of the study was similar for placebo vs. those taking evolocumab, both for total score 3.6% vs. 3.7%, respectively, and for subdomains (memory 5.8% vs. 6% and total executive function 3.6% vs. 3.7%, respectively). The proportion reporting cognitive decline was similar in patients who achieved very low LDL-C levels vs. those with LDL-C ≥100 mg/dL, with scores of 3.8% vs. 4.5%, respectively.
"These data conrm the neurocognitive safety of intensive LDL-C reduction with evolocumab, while simultaneously reducing recurrent cardiovascular events in high-risk patients, and suggest that very low achieved LDL-C levels may be safely targeted for high-risk patients," says Robert P. Giugliano, MD, SM, corresponding author of the study and senior investigator of the TIMI Study Group at Brigham, Women's Hospital and Professor of Medicine at Harvard Medical School in Boston.
The patient-reported outcomes of this comprehensive study in over 22,000 patients build upon the results of the EBBINGHAUS trial, which demonstrated evolocumab added to background statin did not aect cognitive performances using a validated battery of neurocognitive tests performed serially in a subset of 1,204 patients enrolled in the FOURIER trial.
FOURIER was a randomized, double-blind, placebo-controlled trial involving patients with atherosclerotic cardiovascular disease and LDL-C levels ≥70 mg/dL despite statin. At the nal visit, patients completed a 23- item survey on memory and executive domains from the Everyday Cognition scale.
This study has several limitations, including a healthy volunteer bias in the cognitive survey responders, the relatively younger age of the participants, and the low proportion of patients with a history of stroke.
"It is unclear if this expectation of safety can be extrapolated to periods of greater than three years, or to patients who are older than 75 years, are at very high ASCVD risk, or with a history of ischemic or hemorrhagic stroke," says Jennifer G. Robinson, MD, MPH, professor of epidemiology and medicine at the University of Iowa, in an accompanying editorial. "An altered safety prole may inuence the potential for a net cardiovascular risk reduction benet from the addition of PCSK9 mAbs. Longer follow-up and more diverse trial populations are needed."