Physicians' Academy for Cardiovascular Education

Greater risk reduction with PCSK9 inhibition in readily ascertainable high risk patient subgroups

Clinical Benefit of Evolocumab by Severity and Extent of Coronary Artery Disease: An Analysis from FOURIER

Literature - Sabatine MS, De Ferrari GM, Giugliano RP, et al. - Circulation. 2018; published online ahead of print

Introduction and methods

The Further cardiovascular Outcomes Research with PCSK9 Inhibition in patients with Elevated Risk (FOURIER) trial showed that the PCSK9 antibody evolocumab, when added to statin therapy, lowered LDL-c by 59%, and significantly reduced the risk of cardiovascular (CV) events in patients with stable atherosclerotic CV disease, the majority of whom (N= 22,351) had a history of myocardial infarction (MI) [1-4].

This analysis of the FOURIER trial aimed to assess whether common and readily ascertainable features would identify subsets of patients that derive greater clinical risk reduction with evolocumab, for instance based on the timing from the most recent MI, the number of prior MIs, and the presence of residual multi-vessel coronary artery disease (CAD), defined as ≥40% stenosis in ≥2 large vessels.

FOURIER enrolled 27,564 patients aged 40-85 years with clinically evident atherosclerotic CV disease, and additional CV risk factors, as well as LDL-c ≥70 mg/dL or non-HDL-c ≥100 mg/dL while taking an optimized lipid-lowering. Patients received subcutaneous evolocumab (either 140 mg Q2W or 420 mg Q4W) or matching placebo, and were followed for a median of 2.2 years (IQR: 1.8-2.5 years). The primary endpoint of FOURIER was the composite of CV death, MI, stroke, coronary revascularization, or hospitalization for unstable angina. The key secondary endpoint was the composite of CV death, MI, or stroke.

Main results


Patients with a history of MI who are closer to their most recent event, have had multiple prior MIs or have residual multi-vessel CAD are at higher risk for major vascular events. The relative and absolute risk reductions in CV outcomes with evolocumab were greater in these high-risk subgroups. These data support the targeting of such high risk patients with PCSK9 inhibition.


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