Data from the FOURNIER TRIAL: Efficacy and Safety of Evolocumab

San Diego—The FOURIER trial was designed to assess the efficacy and safety of evolocumab in PCSK9 inhibition in patients with chronic kidney disease (CKD); the study analyzed outcomes by kidney function. David M. Charytan, MD, and colleagues reported results of the trial during an oral session at Kidney Week 2018. The session was titled Efficacy and Safety of Evolocumab in CKD: Data from the FOURIER Trial.

A total of 27,564 patients with stable atherosclerosis and low density lipoprotein (LDL) cholesterol (70 mg/dL) or non–high-density cholesterol (100 mg/dL) were randomized to receive evolocumab or placebo. The primary end point of interest was cardiovascular death, myocardial infarction, stroke, hospitalization for unstable angina, or coronary revascularization. Key secondary end points were cardiovascular death, myocardial infarction, or stroke. The end points and death were analyzed by CKD stage from baseline estimated glomerular filtration rate (eGFR) estimated by the CKD-Epidemiology Collaboration equation.

Of the total cohort, 8077 had eGFR ≥90 mL/min/1.73 m2(preserved kidney function group), 15,034 had stage 2 CKD (defined as eGFR 60-89 mL/min/1.73 m2), and 4443 had stage 3 or higher (defined as eGFR <60 mL/min/1.73 m2). Worse CKD stage was associated with increased age and comorbidity prevalence. At 48 weeks, reduction in LDL cholesterol versus placebo was similar across CKD groups: 58.2% in the preserved kidney function group, 59.4% in the CKD stage 2 group, and 58.7% in the stage 3 or higher group.

In the placebo group, the rates of both the primary and secondary end points were higher with worsening CKD, particularly those with stage 3 or higher CKD versus those with preserved kidney function: primary end point, 16.1% vs 12.2%, respectively, P<.01; and secondary, 12.8% vs 7.1%, respectively, P<.001.

The relative risk reduction (RR) seen with evolocumab was similar across CKD stages. However, the absolute RR for the key secondary end point tended to be larger among those with stage 3 or higher CKD (2.5%, 95% confidence interval [CI], 0.4%-4.7%) compared with participants with preserved kidney function (1.7%; 95% CI, 0.5%-2.8%).

Adverse events, including decline in eGFR ≥30%, were similar across CKD stages.

In conclusion, the researchers said, “LDL cholesterol 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 cardiovascular death, myocardial infarction, or stroke tended to be greater with more advanced CKD.”

Source: Charytan DM, Sabatine MS, Pedersen TR, et al. Efficacy and safety of evolocumab in CKD: Data from the FOURIER trial. Abstract of an oral session (FR-OR114) presented at the American Society of Nephrology Kidney Week 2018, October 26, 2018, San Diego, California.

This study was supported by Amgen, Inc.