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Kidney Week

Abstract: FR-OR114

Efficacy and Safety of Evolocumab in CKD: Data from the FOURIER Trial

Session Information

Category: CKD (Non-Dialysis)

  • 1902 CKD (Non-Dialysis): Clinical, Outcomes, and Trials

Authors

  • Charytan, David M., Brigham and Women's Hospital/Harvard Medical School, Brookline, Massachusetts, United States
  • Sabatine, Marc S., TIMI Study Group, Brigham and Women’s Hospital, Boston, Massachusetts, United States
  • Pedersen, Terje R., Oslo University Hospital, Ullevål, Oslo, Norway
  • Im, Kyungah, TIMI Study Group, Brigham and Women’s Hospital, Boston, Massachusetts, United States
  • Lira Pineda, Armando, Amgen, Thousand Oaks, California, United States
  • Wasserman, Scott M., Amgen, Thousand Oaks, California, United States
  • Sever, Peter, Imperial College London, London, United Kingdom
  • Keech, Anthony C., NHMRC Clinical Trials Centre, University of Sydney, Sydney, New South Wales, Australia
  • Giugliano, Robert P., TIMI Study Group, Brigham and Women’s Hospital, Boston, Massachusetts, United States
Background

The efficacy and safety of PCSK9 inhibition in patients (pts) with CKD is undefined. We analyzed outcomes by kidney function in FOURIER.

Methods

FOURIER randomized 27564 pts with stable atherosclerosis and LDL-cholesterol (C) ≥70 or non-HDL-C ≥100 mg/dL to the PCSK9 inhibitor evolocumab or placebo. The primary endpoint (CV death, MI, stroke, hospitalization for unstable angina, or coronary revascularization), key secondary endpoint (CV death, MI or stroke), and safety outcomes were analyzed by CKD stage estimated from baseline CKD-EPI eGFR.

Results

8077 pts had eGFR ≥90 mL/min/1.73m2, 15,034 stage 2 (eGFR 60-89), and 4443 ≥stage 3 CKD (eGFR <60). Age and comorbidity prevalence increased with worse CKD. LDL-C reduction with evolocumab vs placebo at 48 weeks was similar across CKD groups at 58.2%, 59.4% and 58.7%, respectively. In the placebo arm, the primary and key secondary endpoint rates were higher with worsening CKD, especially those with ≥stage 3 vs. preserved kidney function (primary-16.1% vs. 12.2%, P<0.01; secondary-12.8% vs. 7.1%, P<0.001, Figure). Relative risk reduction (RRR) with evolocumab was similar regardless of CKD stage (Pint=0.77 and 0.75, respectively). However, the absolute RRs for the key secondary endpoint tended to be larger among those with ≥stage 3 CKD (2.5%, 95% CI: 0.4%-4.7%) compared with individuals with preserved kidney function (1.7%, 95% CI 0.5%-2.8%). Adverse events, including eGFR decline ≥30%, were similar regardless of CKD stage.

Conclusion

LDL-C lowering and the relative efficacy and safety of evolocumab was preserved across CKD groups in patients with clinically evident atherosclerosis and hyperlipidemia on statin therapy. Absolute reduction in CV death, MI or stroke with evolocumab tended to be greater with more advanced CKD.

Kaplan-Meier event rates at 3-years according to treatment group. (A) Primary endpoint. (B) Key secondary endpoint. ARR-absolute risk reduction. HR-hazard ratio. CI-confidence interval.

Funding

  • Commercial Support