Early initiation of evolocumab reduces complex coronary revascularization

ACC.25 – Early initiation of evolocumab compared with delayed initiation reduced the incidence of complex coronary revascularization in patients with ASCVD during long-term follow-up, according to an analysis of FOURIER and the open-label extension of FOURIER.

This summary is based on the presentation of Paul Haller, MD, PhD (Boston, MA, USA) at the ACC.25 Scientific Session - Evolocumab and complex coronary revascularization during 8-year follow-up: Analysis from the FOURIER and FOURIER OLE trials.

Introduction and methods

High coronary plaque burden is associated with worse long-term outcomes and impacts clinical decision-making. Complex coronary artery disease (CAD) may require complex revascularization. Previously, the FOURIER trial demonstrated that the PCSK9 inhibitor evolocumab reduces the incidence of MACE and complex coronary revascularization in patients with ASCVD. This analysis of open-label extension of FOURIER (FOURIER-OLE) investigated the effect of early versus delayed initiation of evolocumab for complex coronary revascularization during long-term follow-up.

FOURIER was a randomized, double-blind, placebo-controlled trial with 27,564 patients with stable ASCVD. Patients had baseline LDL-c concentrations of ≥70 mg/dL or non-HDL-c levels ≥100 mg/dL while on optimized lipid-lowering therapy, including a high- or moderate-intensity statin with or without ezetimibe. Patients were randomized to subcutaneous evolocumab (either 140 mg every 2 weeks or 420 mg once per month) or placebo. A total of 6635 patients from the FOURIER trial were enrolled in FOURIER-OLE. Patients received subcutaneous evolocumab (either 140 mg every 2 weeks or 420 mg once per month), regardless of initial allocation in the parent trial. The median follow-up period was 2.2 years in FOURIER and 5.0 years in FOURIER-OLE (maximum follow-up up to 8 years).

The primary outcome was complex coronary revascularization, which was defined as complex PCI according to the GLOBAL LEADERS definition or CABG.

Main results

• In FOURIER and FOURIER-OLE, there were a total of 2222 revascularization events, of which 1374 were non-complex PCI (61.8%) and 848 were complex revascularization (38.2%).
• Of the complex revascularization events, 389 were CABG (45.9%) and 459 were complex PCI (54.1%).
• In years 1 to 3 of OLE, the incidence of complex coronary revascularization was lower in patients who had originally been randomized to evolocumab compared with patients who were switched from placebo to evolocumab (HR: 0.86; 95%CI: 0.63–1.17).
• In years 4 to 5 of OLE, the incidence of complex coronary revascularization appeared similar between the two groups (HR: 1.29; 95%CI: 0.79–2.11).
• Overall, there was a relative risk reduction of 24% with early initiation of evolocumab compared with delayed initiation (HR: 0.76; 95%CI: 0.67–0.87; P<0.001).

Conclusion

In this analysis of FOURIER-OLE, long-term treatment with evolocumab (up to 8 years) compared with delayed initiation reduced the incidence of complex coronary revascularization. “This underscores and highlights the benefits of an early initiation of potent LDL-c therapy among patients with established ASCVD,” concluded Paul Haller.

- Our reporting is based on the information provided at the ACC.25 Scientific Session -