BACKGROUND - Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors induce plaque regression and reduce the risk of coronary revascularization overall.

OBJECTIVES - To evaluate the ability of PCSK9 inhibitors to reduce the risk of complex coronary atherosclerosis requiring revascularization.

METHODS - FOURIER was a randomized trial of the PCSK9 inhibitor evolocumab vs. placebo in 27,564 patients with stable atherosclerosis on statin therapy followed for a median of 2.2 years. Clinical documentation of revascularization events was blindly reviewed to assess coronary anatomy and procedural characteristics. Complex revascularization was the composite of complex percutaneous coronary intervention (PCI) (as per previous analyses, >1 of: multivessel PCI, ≥3 stents, ≥3 lesions treated, bifurcation PCI, or total stent length >60 mm) or coronary artery bypass grafting surgery (CABG).

RESULTS - 1,724 patients underwent coronary revascularization, including 1482 who underwent PCI, 296 who underwent CABG, and 54 both. Complex revascularization was performed in 632 (37%) patients. Evolocumab reduced the risk of any coronary revascularization by 22% (HR 0.78 [0.71-0.86]; P<0.001), simple PCI by 22% (HR 0.78, [0.70-0.88]; P<0.001), complex PCI by 33% (HR 0.67 [0.54-0.84]; P<0.001), CABG by 24% (HR 0.76 [0.60-0.96]; P=0.019), and complex revascularization by 29% (HR 0.71 [0.61-0.84]; P<0.001). The magnitude of the risk reduction with evolocumab in complex revascularization tended to increase over time (20%, 36%, and 41% risk reductions in 1^st, 2^nd and beyond 2^nd year).

CONCLUSIONS - Adding evolocumab to statin therapy significantly reduced the risk of developing complex coronary disease requiring revascularization, including complex PCI and CABG individually.