Repatha (Evolocumab) and Muscle Memory Loss
Based on current evidence, Repatha (evolocumab) does not cause muscle memory loss or cognitive impairment, even at very low LDL-C levels. 1
Evidence on Cognitive Function and Evolocumab
The EBBINGHAUS trial, a dedicated cognitive function sub-study of the FOURIER trial, specifically investigated the effect of evolocumab on neurocognitive function:
- The study found no difference in cognitive function between evolocumab/statin vs. statin-only groups at a median of 19 months 1, 2
- The primary endpoint of spatial working memory strategy index of executive function showed no significant difference between evolocumab and placebo groups (P < 0.001 for noninferiority) 1
- No differences were observed in secondary cognitive endpoints including:
- Working memory
- Episodic memory
- Psychomotor speed
Additional Safety Data
- The 2022 ACC Expert Consensus specifically notes: "No evidence of an increase in cognitive adverse effects observed in FOURIER or EBBINGHAUS" 2
- Evolocumab has demonstrated an excellent safety profile in clinical trials and post-marketing surveillance 3
- Common adverse effects reported with evolocumab include:
- Nasopharyngitis
- Upper respiratory tract infection
- Influenza
- Back pain
- Injection site reactions 2
Initial Concerns and Resolution
Initial concerns about potential neurocognitive effects arose because:
- Cholesterol is a major membrane component of brain cells 2
- The OSLER study showed slightly more neurocognitive events in evolocumab/statin vs. statin-only patients (0.9% vs. 0.3%) 2
However, these concerns were addressed by:
- The EBBINGHAUS trial specifically designed to assess cognitive function 1
- Recognition that brain cholesterol regulation primarily depends on local de novo synthesis rather than circulating plasma cholesterol levels 2
Limitations of Current Evidence
While current evidence is reassuring, some limitations should be noted:
- EBBINGHAUS had relatively short follow-up (median 19 months)
- The study enrolled relatively young patients (mean age 63)
- Patients with known dementia or mild cognitive impairment were excluded 2
Clinical Implications
When prescribing Repatha (evolocumab):
- Reassure patients that current evidence does not show cognitive impairment or muscle memory loss
- Monitor for more common side effects like injection site reactions and upper respiratory infections
- Consider that even very low LDL-C levels achieved with evolocumab have not been associated with cognitive decline
In summary, while long-term monitoring for cognitive effects may be prudent in high-risk patients, current evidence strongly supports that Repatha does not cause muscle memory loss or cognitive impairment.