WASHINGTON, DC — Low-density lipoprotein cholesterol (LDL-C) levels were lowered and risk of cardiovascular events reduced with evolocumab on a background of statin therapy, according to results of the FOURIER trial presented at the 66th Annual Scientific Session & Expo of the American College of Cardiology and simultaneously published in the New England Journal of Medicine.1,2
FOURIER (Further Cardiovascular Outcomes Research with PCSK9 Inhibition in Subjects With Elevated Risk; Clinicaltrials.gov identifier: NCT01764633) was a randomized, double-blind, placebo-controlled, multinational clinical trial. A total of 27,564 patients with atherosclerotic cardiovascular disease, LDL-C levels ≥70 mg/dL, and receiving statin therapy 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 a composite of cardiovascular death, myocardial infarction (MI), stroke, hospitalization for unstable angina, or coronary revascularization. The secondary efficacy end point was the composite of cardiovascular death, MI, or stroke. Patients were followed up for a median of 2.2 years.
LDL-C levels were reduced by 59% with evolocumab from a median baseline value of 92 mg/dL to 30 mg/dL (P <.001) at 48 weeks. Evolocumab, relative to placebo, reduced the risk of the primary end point by 15%, which occurred in 9.8% of patients in the treatment group vs 11.3% of patients in the placebo group (hazard ratio [HR]: 0.85; 95% CI, 0.79-0.92; P <.001). The main secondary end point was reduced by 20%, occurring in 5.9% of patients in the treatment group vs 7.4% of patients in the placebo group (HR: 0.80; 95% CI, 0.73-0.88; P <.001).
In terms of safety, there were no significant between-group differences in any adverse events, and consistent benefits were observed across all LDL-C quartiles — from the highest baseline level of 126 mg/dL to the lowest level of 74 mg/dL.
It is important to note that while there were reductions of 21% to 27% in risk of MI, stroke, and coronary revascularization, there was no observed effect on rates of hospitalization for unstable angina, cardiovascular death or hospitalization for worsening heart failure, or death from any cause.
The major study limitation is the relatively short duration of follow-up compared with other lipid-lowering trials that averaged 5 years.
“These findings show that patients with atherosclerotic cardiovascular disease benefit from the lowering of LDL cholesterol levels below current targets,” the researchers concluded.
Disclosures: The FOURIER study was funded by Amgen Pharmaceuticals. Author disclosures are available on NEJM.org.
- Sabatine M, Giugliano RP, Keech AC, et al; for the FOURIER Steering Committee and Investigators. Evolocumab and clinical outcomes in patients with cardiovascular disease [published online March 17, 2017]. N Engl J Med. doi:10.1056/NEJMoa1615664
- Sabatine M; for the FOURIER Steering Committee and Investigators. Primary results of the Further Cardiovascular Outcomes Research With PCSK9 Inhibition in Subjects With Elevated Risk (FOURIER) trial. ACC/JACC Late-Breaker Press Conference. Presented at: The 66th Annual Scientific Session & Expo of the American College of Cardiology. March 17-19, 2017; Washington, DC.