Skip to main content
construction release_alert
Scholars@Duke will be undergoing maintenance April 11-15. Some features may be unavailable during this time.
cancel

Evolocumab and Clinical Outcomes in Patients with Cardiovascular Disease.

Publication ,  Journal Article
Sabatine, MS; Giugliano, RP; Keech, AC; Honarpour, N; Wiviott, SD; Murphy, SA; Kuder, JF; Wang, H; Liu, T; Wasserman, SM; Sever, PS ...
Published in: N Engl J Med
May 4, 2017

BACKGROUND: Evolocumab is a monoclonal antibody that inhibits proprotein convertase subtilisin-kexin type 9 (PCSK9) and lowers low-density lipoprotein (LDL) cholesterol levels by approximately 60%. Whether it prevents cardiovascular events is uncertain. METHODS: We conducted a randomized, double-blind, placebo-controlled trial involving 27,564 patients with atherosclerotic cardiovascular disease and LDL cholesterol levels of 70 mg per deciliter (1.8 mmol per liter) or higher who were receiving statin therapy. Patients were randomly assigned to receive evolocumab (either 140 mg every 2 weeks or 420 mg monthly) or matching placebo as subcutaneous injections. The primary efficacy end point was the composite of cardiovascular death, myocardial infarction, stroke, hospitalization for unstable angina, or coronary revascularization. The key secondary efficacy end point was the composite of cardiovascular death, myocardial infarction, or stroke. The median duration of follow-up was 2.2 years. RESULTS: At 48 weeks, the least-squares mean percentage reduction in LDL cholesterol levels with evolocumab, as compared with placebo, was 59%, from a median baseline value of 92 mg per deciliter (2.4 mmol per liter) to 30 mg per deciliter (0.78 mmol per liter) (P<0.001). Relative to placebo, evolocumab treatment significantly reduced the risk of the primary end point (1344 patients [9.8%] vs. 1563 patients [11.3%]; hazard ratio, 0.85; 95% confidence interval [CI], 0.79 to 0.92; P<0.001) and the key secondary end point (816 [5.9%] vs. 1013 [7.4%]; hazard ratio, 0.80; 95% CI, 0.73 to 0.88; P<0.001). The results were consistent across key subgroups, including the subgroup of patients in the lowest quartile for baseline LDL cholesterol levels (median, 74 mg per deciliter [1.9 mmol per liter]). There was no significant difference between the study groups with regard to adverse events (including new-onset diabetes and neurocognitive events), with the exception of injection-site reactions, which were more common with evolocumab (2.1% vs. 1.6%). CONCLUSIONS: In our trial, inhibition of PCSK9 with evolocumab on a background of statin therapy lowered LDL cholesterol levels to a median of 30 mg per deciliter (0.78 mmol per liter) and reduced the risk of cardiovascular events. These findings show that patients with atherosclerotic cardiovascular disease benefit from lowering of LDL cholesterol levels below current targets. (Funded by Amgen; FOURIER ClinicalTrials.gov number, NCT01764633 .).

Duke Scholars

Altmetric Attention Stats
Dimensions Citation Stats

Published In

N Engl J Med

DOI

EISSN

1533-4406

Publication Date

May 4, 2017

Volume

376

Issue

18

Start / End Page

1713 / 1722

Location

United States

Related Subject Headings

  • PCSK9 Inhibitors
  • Middle Aged
  • Male
  • Least-Squares Analysis
  • Incidence
  • Hypercholesterolemia
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Humans
  • General & Internal Medicine
  • Follow-Up Studies
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Sabatine, M. S., Giugliano, R. P., Keech, A. C., Honarpour, N., Wiviott, S. D., Murphy, S. A., … FOURIER Steering Committee and Investigators, . (2017). Evolocumab and Clinical Outcomes in Patients with Cardiovascular Disease. N Engl J Med, 376(18), 1713–1722. https://doi.org/10.1056/NEJMoa1615664
Sabatine, Marc S., Robert P. Giugliano, Anthony C. Keech, Narimon Honarpour, Stephen D. Wiviott, Sabina A. Murphy, Julia F. Kuder, et al. “Evolocumab and Clinical Outcomes in Patients with Cardiovascular Disease.N Engl J Med 376, no. 18 (May 4, 2017): 1713–22. https://doi.org/10.1056/NEJMoa1615664.
Sabatine MS, Giugliano RP, Keech AC, Honarpour N, Wiviott SD, Murphy SA, et al. Evolocumab and Clinical Outcomes in Patients with Cardiovascular Disease. N Engl J Med. 2017 May 4;376(18):1713–22.
Sabatine, Marc S., et al. “Evolocumab and Clinical Outcomes in Patients with Cardiovascular Disease.N Engl J Med, vol. 376, no. 18, May 2017, pp. 1713–22. Pubmed, doi:10.1056/NEJMoa1615664.
Sabatine MS, Giugliano RP, Keech AC, Honarpour N, Wiviott SD, Murphy SA, Kuder JF, Wang H, Liu T, Wasserman SM, Sever PS, Pedersen TR, FOURIER Steering Committee and Investigators. Evolocumab and Clinical Outcomes in Patients with Cardiovascular Disease. N Engl J Med. 2017 May 4;376(18):1713–1722.

Published In

N Engl J Med

DOI

EISSN

1533-4406

Publication Date

May 4, 2017

Volume

376

Issue

18

Start / End Page

1713 / 1722

Location

United States

Related Subject Headings

  • PCSK9 Inhibitors
  • Middle Aged
  • Male
  • Least-Squares Analysis
  • Incidence
  • Hypercholesterolemia
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Humans
  • General & Internal Medicine
  • Follow-Up Studies