Abstract 14566: Long-Term Efficacy of Evolocumab in Patients With and Without Multivessel Coronary Artery Disease

Abstract

Background: In FOURIER, the magnitude of reduction in risk of major adverse cardiovascular events (MACE) was larger in patients with multivessel disease (MVD) than in those without. However, the median follow-up was only 2.2 yrs. The open-label extension (FOURIER-OLE) allows for a better assessment of the long-term benefit of intensive lipid-lowering in these two subgroups. Methods: Patients with CAD at time of enrollment in the parent FOURIER trial were categorized based on the presence or absence of MVD (≥40% stenosis in ≥2 large vessels). Primary endpoint (PEP; CV death, MI, stroke, hospitalization for UA, or coronary revascularization) and key secondary endpoint (SEP; CV death, MI, or stroke) were assessed through FOURIER and FOURIER-OLE, during which all patients received evolocumab. Results: At enrollment in FOURIER, 23,674 patients had CAD, of whom 25% had MVD (N=6007). In the placebo arm, those with MVD had a higher risk of the PEP (HR 1.45 [95%CI 1.32-1.60], P<0.0001) & SEP (HR 1.37 [1.22-1.56], P<0.0001) than those without MVD. The magnitude of the overall relative risk reduction in those initially randomized to evolocumab tended to be greater in patients with MVD than in those without (RRR 23% vs. 12% for PEP; 30% vs. 15% for SEP; P int 0.07 & 0.04, respectively). The magnitude of benefit tended to grow over the first several years (Fig). This was especially true for CV death, in which for patients with MVD, initial randomization to evolocumab reduced the risk of CV death in the later years (HR 0.70 [0.51-0.97]; Fig bottom). Conclusion: Evolocumab reduced the rate of MACE in patients with and without MVD, with earlier and larger benefit seen in patients with MVD. The magnitude of benefit grew over time, supporting early initiation of intensive LDL-C lowering both in patients with and without MVD.