Abstract 14770: Reduction With Evolocumab in Complex Coronary Disease Requiring Revascularization: Insights From the FOURIER Trial

Introduction: Although PCSK9 inhibitors induce plaque regression and reduce the risk of coronary revascularization overall, their ability to specifically reduce the risk of complex coronary atherosclerosis requiring revascularization has not been explored. Methods: FOURIER was a randomized trial of the PCSK9 inhibitor evolocumab vs. placebo in 27,564 patients with ASCVD on statin therapy (median achieved LDL-C 32 mg/dL vs. 89 mg/dL) followed for a median of 2.2 years. The study database was blindly reviewed to assess characteristics of coronary revascularization procedures. Complex revascularization was the composite of complex PCI (per GLOBAL LEADERS criteria, at least one of: multivessel PCI, 3 or more stents implanted, 3 or more lesions treated, bifurcation PCI with 2 or more stents, or total stent length >60 mm) or CABG. PCI complications included no-reflow, side branch loss, thrombus formation, major dissection, or perforation. The effects of evolocumab on types of revascularization and PCI complications were evaluated using Cox proportional hazards models. Results: 1724 patients underwent revascularization procedures during follow-up. Evolocumab reduced the risk of non-complex PCI by 22% (HR 0.78; 95%CI 0.70-0.88; P<0.001) and the risk of complex revascularization by 29% (HR 0.71; 95%CI 0.61-0.84; P<0.001), including complex PCI by 33% (HR 0.67; 95%CI 0.54-0.84; P<0.001) and CABG by 24% (HR 0.76; 95%CI 0.60-0.96; P=0.019; Figure). The incidence of reported PCI complications tended to be lower with evolocumab (HR 0.74; 95% CI 0.49-1.11). Conclusions: Adding evolocumab to statin therapy reduced the risk of developing complex coronary disease requiring revascularization, including complex PCI and CABG individually. Together with prior coronary imaging findings, these data suggest very aggressive LDL-C lowering to <1 mmol/L has beneficial effects on coronary atherosclerosis burden, anatomical complexity, and the need for intervention.