FOURIER — Evolocumab (PCSK9 Inhibitor) in ASCVD

Design

FOURIER randomised 27,564 patients with established ASCVD and LDL ≥70 mg/dL despite statin therapy to evolocumab (a PCSK9-inhibiting monoclonal antibody) or placebo, median follow-up 2.2 years.

Findings

• Median LDL fell from 92 mg/dL to 30 mg/dL on evolocumab.
• Primary composite (cardiovascular death, MI, stroke, hospitalisation for unstable angina, coronary revascularisation): 15% relative reduction.
• Key secondary (cardiovascular death, MI, or stroke): 20% reduction.
• No safety signal at the very low LDL levels achieved (no excess cognitive issues, cataracts, or haemorrhagic stroke).

The FOURIER open-label extension and FOURIER-OLE continued to show benefit with longer follow-up.

Why it matters

FOURIER extended the principle “lower LDL is better, with the magnitude of event reduction proportional to LDL lowering and exposure time” into the very-low-LDL range, and demonstrated no safety floor at LDL ~30 mg/dL.

Practical implication

In high-risk ASCVD patients on maximum-tolerated statin + ezetimibe, PCSK9 inhibitors are an evidence-based add-on. Cost has been the main barrier; biosimilars and inclisiran (a siRNA-based PCSK9 inhibitor with twice-yearly dosing) are expanding access.

Related entries

Statins, ApoB, Cardiovascular disease.