Open-label extension · Circulation 2022
FOURIER-OLE trial
Long-Term Evolocumab in Patients With Established Atherosclerotic Cardiovascular Disease.
The bottom line
Long-term evolocumab treatment after FOURIER maintained very low LDL-C with a persistently favorable safety profile over more than 8 years, and earlier initiation of evolocumab was associated with fewer cardiovascular events, including cardiovascular death, compared with delayed treatment start.
Long-term safety; benefit sustainedUS status: US-approved
At a glance
- Medicine
- Open-label evolocumab (patients originally randomized to evolocumab or placebo in parent trial continued/initiated evolocumab)
- Compared with
- Original parent-trial randomization group (evolocumab vs placebo during parent FOURIER study, before open-label evolocumab initiation)
- People
- 6,635
- Who took part
- Patients with atherosclerotic cardiovascular disease and LDL-C ≥70 mg/dL on statin who completed the parent FOURIER trial at participating sites
- Design
- Open-label extension (pooled analysis of two open-label extension studies) following randomized, parent trial (FOURIER)
- Follow-up
- Median follow-up in FOURIER-OLE was 5.0 years; maximum exposure to evolocumab in parent plus FOURIER-OLE was 8.4 years
- Main question
- Incidence of adverse events
Main result
Incidences of serious adverse events, muscle-related events, new-onset diabetes, hemorrhagic stroke, and neurocognitive events with evolocumab long term did not exceed those for placebo-treated patients during the parent study and did not increase over time
Effect on LDL cholesterol
At 12 weeks in FOURIER-OLE, median LDL-C was 30 mg/dL, and 63.2% of patients achieved LDL-C <40 mg/dL on evolocumab
Other results
A 23% lower risk of cardiovascular death (hazard ratio, 0.77 [95% CI, 0.60-0.99]; P=0.04); also 15% lower risk of CV death/MI/stroke/hospitalization for unstable angina or coronary revascularization (HR 0.85 [0.75-0.96]; P=0.008) and 20% lower risk of CV death, MI, or stroke (HR 0.80 [0.68-0.93]; P=0.003)
Safety
Incidences of serious adverse events, muscle-related events, new-onset diabetes, hemorrhagic stroke, and neurocognitive events with evolocumab long term did not exceed those for placebo-treated patients during the parent study and did not increase over time
In the trial's own words
“During the FOURIER-OLE follow-up period, patients originally randomized in the parent trial to evolocumab versus placebo had a 15% lower risk of cardiovascular death, myocardial infarction, stroke, or hospitalization for unstable angina or coronary revascularization (hazard ratio, 0.85 [95% CI, 0.75-0.96]; P=0.008); a 20% lower risk of cardiovascular death, myocardial infarction, or stroke (hazard ratio, 0.80 [95% CI, 0.68-0.93]; P=0.003); and a 23% lower risk of cardiovascular death (hazard ratio, 0.77 [95% CI, 0.60-0.99]; P=0.04).”
Quoted from the abstract of Circulation 2022, checked word for word against PubMed. PubMed 36031810 · Full paper (DOI)
How this medicine works, where it stands and what it costs: Evolocumab (Repatha) and alirocumab (Praluent)
Common questions
What did the FOURIER-OLE trial find?
Long-term evolocumab treatment after FOURIER maintained very low LDL-C with a persistently favorable safety profile over more than 8 years, and earlier initiation of evolocumab was associated with fewer cardiovascular events, including cardiovascular death, compared with delayed treatment start.
Who was in FOURIER-OLE?
6,635 people. Patients with atherosclerotic cardiovascular disease and LDL-C ≥70 mg/dL on statin who completed the parent FOURIER trial at participating sites.
What was FOURIER-OLE's main result?
Incidences of serious adverse events, muscle-related events, new-onset diabetes, hemorrhagic stroke, and neurocognitive events with evolocumab long term did not exceed those for placebo-treated patients during the parent study and did not increase over time
How much did LDL cholesterol change in FOURIER-OLE?
At 12 weeks in FOURIER-OLE, median LDL-C was 30 mg/dL, and 63.2% of patients achieved LDL-C <40 mg/dL on evolocumab
Related trials
- HUYGENS (2022)Adding evolocumab to statin therapy after NSTEMI led to greater regression and stabilization of coronary plaque on imaging (thicker fibrous caps, smaller lipid cores, less plaque burden) compared with placebo.
- PACMAN-AMI (2022)Adding alirocumab to high-intensity statin therapy after acute MI led to significantly greater regression of coronary plaque burden, lipid content, and thickening of fibrous caps over 52 weeks, with similar adverse event rates to placebo.
- LIBerate-HeFH (2023)In patients with heterozygous familial hypercholesterolaemia needing more LDL-C lowering, adding monthly subcutaneous lerodalcibep to therapy produced a large, highly significant LDL-C reduction versus placebo over 24 weeks with a safety profile similar to placebo aside from mild injection site reactions.
- MK-0616 phase 2b (2023)In this phase 2b trial, the oral PCSK9 inhibitor MK-0616 produced large, dose-dependent LDL-C reductions compared with placebo and was well tolerated over 8 weeks of treatment plus 8 weeks of follow-up.
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