Safety/tolerability RCT · N Engl J Med 2017
EBBINGHAUS trial
Cognitive Function in a Randomized Trial of Evolocumab.
The bottom line
Adding evolocumab to statin therapy did not worsen cognitive function compared with placebo over a median follow-up of 19 months.
No excess harm vs placeboUS status: US-approved
At a glance
- Medicine
- Evolocumab added to statin therapy
- Compared with
- Placebo added to statin therapy
- People
- 1,204
- Who took part
- Subgroup of patients from a randomized, placebo-controlled trial of evolocumab added to statin therapy, with prospective cognitive function assessment
- Design
- randomized, placebo-controlled trial (noninferiority analysis for primary endpoint)
- Follow-up
- median of 19 months
- Main question
- Mean change from baseline in score on the spatial working memory strategy index of executive function (noninferiority comparison)
Main result
the mean (±SD) change from baseline over time in the raw score for the spatial working memory strategy index of executive function (primary end point) was -0.21±2.62 in the evolocumab group and -0.29±2.81 in the placebo group (P<0.001 for noninferiority; P=0.85 for superiority)
Effect on LDL cholesterol
In an exploratory analysis, there were no associations between LDL cholesterol levels and cognitive changes.
Other results
There were no significant between-group differences in the secondary end points of scores for working memory (change in raw score, -0.52 in the evolocumab group and -0.93 in the placebo group), episodic memory (change in raw score, -1.53 and -1.53, respectively), or psychomotor speed (change in raw score, 5.2 msec and 0.9 msec, respectively).
Safety
No significant between-group differences in cognitive secondary endpoints reported; no other safety data provided in abstract.
In the trial's own words
“the mean (±SD) change from baseline over time in the raw score for the spatial working memory strategy index of executive function (primary end point) was -0.21±2.62 in the evolocumab group and -0.29±2.81 in the placebo group (P<0.001 for noninferiority; P=0.85 for superiority).”
Quoted from the abstract of N Engl J Med 2017, checked word for word against PubMed. PubMed 28813214 · Full paper (DOI)
How this medicine works, where it stands and what it costs: Evolocumab (Repatha) and alirocumab (Praluent)
Common questions
What did the EBBINGHAUS trial find?
Adding evolocumab to statin therapy did not worsen cognitive function compared with placebo over a median follow-up of 19 months.
Who was in EBBINGHAUS?
1,204 people. Subgroup of patients from a randomized, placebo-controlled trial of evolocumab added to statin therapy, with prospective cognitive function assessment.
What was EBBINGHAUS's main result?
the mean (±SD) change from baseline over time in the raw score for the spatial working memory strategy index of executive function (primary end point) was -0.21±2.62 in the evolocumab group and -0.29±2.81 in the placebo group (P<0.001 for noninferiority; P=0.85 for superiority)
How much did LDL cholesterol change in EBBINGHAUS?
In an exploratory analysis, there were no associations between LDL cholesterol levels and cognitive changes.
Related trials
- FOURIER (2017)Adding evolocumab to statin therapy substantially lowers LDL cholesterol and reduces cardiovascular events in patients with atherosclerotic cardiovascular disease, with injection-site reactions being the main added safety concern.
- ORION-1 (2017)In this phase 2 trial, inclisiran produced substantial, dose-dependent, and durable reductions in LDL cholesterol and PCSK9 levels in high cardiovascular risk patients, with an acceptable safety profile, but the trial was not designed to assess cardiovascular outcomes.
- SPIRE-1/2 (2017)Bococizumab substantially lowered LDL cholesterol but showed no significant reduction in major cardiovascular events overall, with benefit seen only in the higher-risk trial, and the drug's development was discontinued due to high rates of antidrug antibodies and injection-site reactions.
- GAUSS-3 (2016)In statin-intolerant patients, evolocumab produced substantially greater LDL-C lowering than ezetimibe over 24 weeks, with fewer treatment discontinuations for muscle symptoms.
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