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Evolocumab in Chronic Kidney Disease in the FOURIER Trial
Study Questions:
Is the PCSK9 inhibitor evolocumab effective in reducing cardiac outcomes among patients with chronic kidney disease (CKD)?
Methods:
Data from the FOURIER (Further Cardiovascular Outcomes Research With PCSK9 Inhibition in Subjects With Elevated Risk) trial were used for the present analysis. Participants with clinically evident atherosclerosis and low-density lipoprotein cholesterol (LDL-C) ≥70 mg/dl or non–high-density lipoprotein cholesterol ≥100 mg/dl were randomized to evolocumab or placebo. The primary outcomes were a combined endpoint of cardiovascular death, myocardial infarction, stroke, hospitalization for unstable angina, or coronary revascularization. Secondary outcomes included cardiovascular death, myocardial infarction, or stroke, and safety. Each outcome was examined by CKD stage estimated from CKD-epidemiology estimated glomerular filtration rate.
Results:
A total of 27,554 participants were included in this analysis (8,077 patients with preserved kidney function, 15,034 with stage 2 CKD, and 4,443 with ≥ stage 3 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 reduction for the primary endpoint 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). Relative risk reduction for the secondary endpoint was similar for preserved function (HR, 0.75; 95% CI, 0.62-0.90), stage 2 (HR, 0.82; 95% CI, 0.72-0.93), stage ≥3 (HR, 0.79; 95% CI, 0.65-0.95). Absolute relative risks at 30 months for the secondary endpoint 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.
Conclusions:
The investigators concluded that LDL-C lowering and relative clinical efficacy and safety of evolocumab versus placebo were consistent across CKD groups. Absolute reduction in the composite of cardiovascular death, MI, or stroke with evolocumab was numerically greater with more advanced CKD.
Perspective:
These data support the safety and efficacy of evolocumab regardless of CKD stage among patients with clinical atherosclerosis. Given the risk of CVD among patients with CKD, these findings have clinical relevance. However, it should be noted that numbers of participants with advanced CKD were limited; thus, additional evaluation in this group is warranted.
Clinical Topics: Cardiac Surgery, Cardiovascular Care Team, Diabetes and Cardiometabolic Disease, Dyslipidemia, Invasive Cardiovascular Angiography and Intervention, Prevention, Cardiac Surgery and Arrhythmias, Lipid Metabolism, Nonstatins, Novel Agents
Keywords: Angina, Unstable, Antibodies, Monoclonal, Atherosclerosis, Cholesterol, LDL, Dyslipidemias, Glomerular Filtration Rate, Kidney Diseases, Lipoproteins, Metabolic Syndrome, Myocardial Infarction, Myocardial Revascularization, Proprotein Convertases, Primary Prevention, Renal Insufficiency, Chronic, Risk, Stroke
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