Repatha Sleep Architecture Impact: What the Evidence Actually Shows

Q: Which side effects were reported in the 52-week trial?

In the label's 52-week placebo-controlled trial of 599 people on evolocumab and 302 on placebo: nasopharyngitis 10.5% vs 9.6%, headache 4.0% vs 3.6%, dizziness 3.7% vs 2.6%; discontinuation was 2.2% vs 1.0%, with myalgia the most common reason (0.3% vs 0%) [1].

Q: What did EBBINGHAUS find?

Evolocumab was non-inferior to placebo on the spatial working memory strategy index of executive function (mean change -0.21 vs -0.29, P<0.001) over a median 19 months, and the label adds non-inferiority on selected other cognitive domains [4][1].

Q: How long does evolocumab stay in the body?

The effective half-life is 11 to 17 days, with median peak concentration 3 to 4 days after a single subcutaneous dose and absolute bioavailability of about 72% [1].

By HealthRX.com Editorial Team

Published Jan 28, 2025Updated Nov 7, 2026Last reviewed Jan 28, 2025

4 linked public sourcesEditorial, sourcing, and corrections policy

At a glance

Drug / evolocumab (Repatha), a PCSK9 inhibitor given by subcutaneous injection [1]
Dosing / 140 mg every 2 weeks or 420 mg once monthly [1]
Boxed warning / none; only Warnings and Precaution is hypersensitivity including angioedema [1]
Half-life / effective half-life 11 to 17 days [1]
Cognitive substudy / EBBINGHAUS: non-inferior to placebo on executive function [4]
Common reactions, 52-week trial / nasopharyngitis 10.5% vs 9.6%; headache 4.0% vs 3.6% [1]

Did any trial measure sleep stages?

Sleep architecture is the staged structure of a night: time in REM and in each non-REM stage, how quickly sleep begins and how often it breaks. It takes polysomnography or a comparable recording to measure.

The two large evolocumab outcome trials had cardiovascular primary endpoints. FOURIER randomized 27,564 adults with atherosclerotic cardiovascular disease and LDL-C of 70 mg/dL or higher on statin therapy to evolocumab 140 mg every 2 weeks or 420 mg monthly, or placebo, with a median follow-up of 2.2 years [2]. VESALIUS-CV randomized 12,257 adults with atherosclerosis or diabetes and no prior myocardial infarction or stroke to evolocumab 140 mg every 2 weeks or placebo, followed over a median 4.6 years [3].

What the trials recorded instead

The label reports adverse reactions from a 52-week placebo-controlled trial of 420 mg monthly (599 on evolocumab vs 302 on placebo): nasopharyngitis 10.5% vs 9.6%, injection-site reactions 5.7% vs 5.0%, headache 4.0% vs 3.6%, myalgia 4.0% vs 3.0%, dizziness 3.7% vs 2.6% [1]. Discontinuation was 2.2% vs 1.0%, with myalgia the most common reason (0.3% vs 0%) [1]. These are percentages of participants reporting each event. The FOURIER paper reported no significant difference in adverse events apart from injection-site reactions (2.1% vs 1.6%) [2].

EBBINGHAUS, a cognitive substudy of FOURIER, enrolled 1,974 patients per the label; the publication followed 1,204 of them for a median of 19 months [4][1]. Mean change on the spatial working memory strategy index of executive function was -0.21 with evolocumab vs -0.29 with placebo, meeting a non-inferiority margin of 20% of the placebo standard deviation (P<0.001), and the label adds non-inferiority on selected other cognitive domains [4][1].

What the label says about warnings and duration

The label says to stop treatment and treat if serious hypersensitivity symptoms occur [1]. Evolocumab has an effective half-life of 11 to 17 days [1].

Frequently asked questions

Which side effects were reported in the 52-week trial?