Effect of Evolocumab on Complex Coronary Disease Requiring Revascularization.

Objectives: This study sought to evaluate the ability of the proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor evolocumab to reduce the risk of complex coronary atherosclerosis requiring revascularization.
Background: PCSK9 inhibitors induce plaque regression and reduce the risk of coronary revascularization overall.
Methods: FOURIER (Further Cardiovascular Outcomes Research with PCSK9 Inhibition in Subjects with Elevated Risk) was a randomized trial of the PCSK9 inhibitor evolocumab versus placebo in 27,564 patients with stable atherosclerotic cardiovascular disease 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: In this study, 1,724 patients underwent coronary revascularization, including 1,482 who underwent PCI, 296 who underwent CABG, and 54 who underwent both. Complex revascularization was performed in 632 (37%) patients. Evolocumab reduced the risk of any coronary revascularization by 22% (hazard ratio [HR]: 0.78; 95% CI: 0.71 to 0.86; p < 0.001), simple PCI by 22% (HR: 0.78; 95% CI: 0.70 to 0.88; p < 0.001), complex PCI by 33% (HR: 0.67; 95% CI: 0.54 to 0.84; p < 0.001), CABG by 24% (HR: 0.76; 95% CI: 0.60 to 0.96; p = 0.019), and complex revascularization by 29% (HR: 0.71; 95% CI: 0.61 to 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 the first, second, and beyond second years).
Conclusions: Adding evolocumab to statin therapy significantly reduced the risk of developing complex coronary disease requiring revascularization, including complex PCI and CABG individually. (Further Cardiovascular Outcomes Research with PCSK9 Inhibition in Subjects with Elevated Risk (FOURIER); NCT01764633.).
Competing Interests: Author Disclosures The FOURIER trial was supported by Amgen. Dr. Oyama has received a grant from JSPS Overseas Research Fellowships. Dr. Furtado has received grants and personal fees from AstraZeneca and Bayer; has received personal fees from Servier; and has received research grants from Pfizer, EMS, Aché, Brazilian Ministry of Health, University Health Network, and Lemann Foundation Research Fellowship. Dr. Fagundes has received a grant from The Lemann Foundation as Research Fellowships. Dr. Zelniker has received honoraria from AstraZeneca and Boehringer Ingelheim; and has received research grants from the German Research Foundation and the Austrian Science Funds. Drs. Tang, Kuder, Murphy, and Bergmark are members of the TIMI Study Group, which has received institutional grant support through the Brigham and Women’s Hospital from Abbott, Amgen, Aralez, AstraZeneca, Bayer HealthCare Pharmaceuticals, Inc., Daiichi-Sankyo, Eisai, GlaxoSmithKline, Intarcia, Janssen, MedImmune, Merck, Novartis, Pfizer, Poxel, Quark Pharmaceuticals, Roche, Takeda, The Medicines Company, and Zora Biosciences. Dr. Hamer is an employee of Amgen. Dr. Wang is an employee of Amgen. Dr. Keech has received grants and personal fees from Abbott; has received personal fees from Amgen, AstraZeneca, and Pfizer; has received grants and personal fees from Mylan; has received grants from Sanofi andNovartis, outside the submitted work; and has received personal fees from Bayer, outside the submitted work. Dr. Giugliano has received grants from Amgen; has received honoraria from Amgen, AstraZeneca, Daiichi-Sankyo, Dr. Reddy’s Laboratories, and Merck; and has received consultant fees from Amgen, Akcea, Amarin, Boehringer Ingelheim, Bristol Myers Squibb, CVS Caremark, Daiichi-Sankyo, Esperion, GlaxoSmithKline, Lexicon, Merck, Portola, and Pfizer. Dr. Sabatine has received research grant support through Brigham and Women’s Hospital from Amgen, AstraZeneca, Daiichi-Sankyo, Eisai, Intarcia, The Medicines Company, MedImmune, Merck, Novartis, and Pfizer; has received consulting fees from Althera, Amgen, Anthos Therapeutics, AstraZeneca, Bristol Myers Squibb, DalCor, Dr. Reddy’s Laboratories, Intarcia, and Merck. Dr. Bergmark has received grant support from Pfizer, AstraZeneca, and Abbott Vascular; and has received consulting fees from Philips, Abbott Vascular, Servier, Daiichi-Sankyo, Janssen, and Quark.
(Copyright © 2021 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)