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Cited by 410Lipoproteins and Cardiovascular HealthAtherosclerosis and Cardiovascular DiseasesAcute Myocardial Infarction Research

Long-term evolocumab in patients with established atherosclerotic cardiovascular disease

O’Donoghue, Michelle L., Giugliano, Robert P., Wiviott, Stephen D., Atar, Dan, Keech, Anthony, Kuder, Julia F., Im, KyungAh, Murphy, Sabina A. +7 more·2022·Circulation
DOI 10.1161/circulationaha.122.061620
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Abstract

Background: In FOURIER (Further Cardiovascular Outcomes Research With PCSK9 Inhibition in Subjects With Elevated Risk), the proprotein convertase subtilisin-kexin type 9 inhibitor evolocumab reduced low-density lipoprotein cholesterol (LDL-C) and risk of cardiovascular events and was safe and well tolerated over a median of 2.2 years of follow-up. However, large-scale, long-term data are lacking. Methods: The parent FOURIER trial randomized 27 564 patients with atherosclerotic cardiovascular disease and LDL-C ≥70 mg/dL on statin to evolocumab versus placebo. Patients completing FOURIER at participating sites were eligible to receive evolocumab in 2 open-label extension studies (FOURIER-OLE [FOURIER Open-Label Extension]) in the United States and Europe; primary analyses were pooled across studies. The primary end point was the incidence of adverse events. Lipid values and major adverse cardiovascular events were prospectively collected. Results: A total of 6635 patients were enrolled in FOURIER-OLE (3355 randomized to evolocumab and 3280 to placebo in the parent study). Median follow-up in FOURIER-OLE was 5.0 years; maximum exposure to evolocumab in parent plus FOURIER-OLE was 8.4 years. 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. 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. 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). Conclusions: Long-term LDL-C lowering with evolocumab was associated with persistently low rates of adverse events for >8 years that did not exceed those observed in the original placebo arm during the parent study and led to further reductions in cardiovascular events compared with delayed treatment initiation. Registration: URL: https://www.clinicaltrials.gov ; Unique identifiers: NCT02867813 and NCT03080935.

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  • The FOURIER open-label extension study reported a 14.0% overall premature discontinuation rate over 5 years among 6,635 patients randomized to evolocumab.

    “Regarding the persistence phase, the FOURIER open-label extension study reported a 14.0% overall premature discontinuation rate over 5 years among 6,635 patients randomized to evolocumab.115,116”

    From Adherence to PCSK9 Inhibitors in Clinical Practice (2026) · cites this paper as [116]

    The Results report 14.0% premature study-drug discontinuation among patients originally randomized to evolocumab. They also state that 6,635 patients enrolled in FOURIER-OLE, but only 3,355 of them had been randomized to evolocumab in the parent trial; the other 3,280 had been randomized to placebo. Median follow-up in the extension was 5.0 years. Thus, the rate and timeframe are supported, but the claimed group of 6,635 randomized to evolocumab is not. (LLM, conf=0.92)

    Experimental — accuracy not yet measured

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Authors
O’Donoghue, M. L., Giugliano, R. P., Wiviott, S. D., Atar, D., Keech, A., Kuder, J. F., Im, K., Murphy, S. A., Flores-Arredondo, J. H., López, J. A. G., Elliott-Davey, M., Wang, B., Monsalvo, M. L., Abbasi, S., & Sabatine, M. S.
Affiliations
  • Brigham and Women's Hospital (US)
  • Oslo University Hospital (NO)
  • Global Development, Amgen, Thousand Oaks, CA (J.H.F.-A., J.A.G.L., B.W., M.L.M., S.A.).
  • Amgen (United States) (US)
  • Amgen Ltd, Cambridge, United Kingdom (M.E.-D.).
Corresponding author
O’Donoghue, Michelle L.
ORCID
Venue
Circulation
Publisher
Ovid Technologies (Wolters Kluwer Health)
Published
2022-10-11
Volume
146
Issue
15
Pages
1109-1119
ISSN
  • 0009-7322 (ISSN-L)
  • 1524-4539
DOI
10.1161/circulationaha.122.061620
OpenAlex
W4293426420
Cited by
410
References
6
Citations by year
2026: 83 · 2025: 101 · 2024: 111 · 2023: 98 · 2022: 17
FWCI
78.31
Type
journal article
Language
en
Open access
closed
Locations
  • Circulation (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Health Sciences › Medicine › Surgery › Lipoproteins and Cardiovascular Health
  • Life Sciences › Immunology and Microbiology › Immunology › Atherosclerosis and Cardiovascular Diseases
  • Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Acute Myocardial Infarction Research
Keywords
evolocumab, PCSK9 inhibition, atherosclerotic cardiovascular disease, LDL cholesterol lowering, long-term safety, adverse events, major adverse cardiovascular events, FOURIER trial, open-label extension, statin-treated patients
MeSH terms
Proprotein Convertase 9, PCSK9 Inhibitors, Antibodies, Monoclonal, Anticholesteremic Agents, Cardiovascular Diseases, Humans, Cholesterol, LDL, Myocardial Infarction, Subtilisins, Treatment Outcome, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Stroke, Atherosclerosis, Antibodies, Monoclonal, Humanized

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