Evolocumab Safely Reduces Risk for CV Events in Chronic Kidney Disease

Evolocumab used along with statins is effective in reducing low-density lipoprotein cholesterol (LDL-C) and the risk for cardiovascular events in individuals with moderate chronic kidney disease (CKD), according to a study published in Journal of the American College of Cardiology.

The Further Cardiovascular Outcomes Research with proprotein convertase subtilisin-kexin type 9 (PCSK9) Inhibition in Subjects with Elevated Risk (FOURIER) trial included adults aged 40 to 85 with acute coronary syndrome and additional cardiovascular risk factors and a fasting LDL-C level ≥70 mg/dL or non-high-density lipoprotein cholesterol ≥100 mg/dL. Additionally, participants were on a high- or moderate-intensity statin (defined as equivalent to a dose of atorvastatin ≥20 mg daily). Those with an estimated glomerular filtration rate (eGFR) <20 mL/min/1.73 m² or a history of renal transplantation were excluded.

Those enrolled were randomly assigned to receive double-blind evolocumab (140 mg every 2 weeks or 420 mg monthly) or matching placebo in a 1:1 ratio. The primary end point was the composite of cardiovascular death, myocardial infarction (MI), stroke, hospitalization for unstable angina, or coronary revascularization. Key secondary end points were cardiovascular death, MI, or stroke according to the estimated CKD stage.

Out of 27,564 adults enrolled in the trial, there were 8077 with preserved kidney function, 15,034 with stage 2 CKD, and 4443 with stage 3 or above CKD. LDL-C reduction with evolocumab compared with placebo at 48 weeks was similar across CKD groups at 59%, 59%, and 58%, respectively. Relative risk (RR) reduction for the primary end point was similar for preserved function (hazard ratio [HR] 0.82; 95% CI, 0.71-0.94), stage 2 (HR 0.85; 95% CI, 0.77-0.94), and stage ≥3 CKD (HR 0.89; 95% CI, 0.76-1.05); Pinteraction =0.77.

RR reduction for the secondary end point was similar across CKD stages (Pinteraction =0.75): preserved function (HR 0.75; 95% CI, 0.62-0.9), stage 2 (HR 0.82; 95% CI, 0.72-0.93), and stage ≥3 (HR 0.79; 95% CI, 0.65-0.95).

Absolute RRs at 30 months for the secondary end point were -2.5% (95% CI, -0.4% to -4.7%) for stage ≥3 CKD compared with -1.7% (95% CI, 0.5% to -2.8%) with preserved kidney function.

Adverse events, including estimated glomerular filtration rate decline, were infrequent and similar regardless of CKD stage.

Because only a few adults were enrolled with stage 4 or 5 CKD and those with eGFR <20 mL/min/1.73 m2 were excluded, these results may not be generalizable to those with end-stage renal disease or atherosclerosis. Another limitation was that the overall follow-up was only 2.2 years, which was a very short period to be able to detect the effect of CKD progression on outcomes.

The researchers concluded that in stable individuals with moderate CKD and clinically evident atherosclerosis, acute coronary syndrome, and hyperlipidemia, PCSK9 inhibition with evolocumab was safe and more effective than statin monotherapy in reducing LDL-C and the risk for cardiovascular events. It was recommended that further cardiovascular outcomes trials be conducted which examine the benefits of evolocumab in individuals with CKD, especially among those with severely reduced eGFR.

The FOURIER trial was funded by Amgen, Inc. Please refer to reference for a complete list of authors’ disclosures.

Reference

Charytan DM, Sabatine MS, Pedersen TR, et al. Efficacy and safety of evolocumab in chronic kidney disease in the FOURIER trial. J Am Coll Cardiol. 2019;73(23):2961-2970.