Disclosures: Oyama reports he received a grant from JSPS Overseas Research Fellowships. Bergmark reports he received grant support from Abbott Vascular, AstraZeneca and Pfizer and has received consulting fees from Abbott Vascular, Daiichi-Sankyo, Janssen, Philips, Quark and Servier. Please see the study for all other authors’ relevant financial disclosures. Ohman reports he received research grants from Abiomed and Cheisi USA and consulted for Abiomed, Cara Therapeutics, Chiesi USA, Cytokinetics, Imbria Pharmaceuticals, Otsuka Pharmaceuticals, Milestone Pharmaceuticals and XyloCor Therapeutics. Nanna reports no relevant financial disclosures.
January 20, 2021
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Evolocumab may reduce likelihood of future revascularization in established ASCVD

Disclosures: Oyama reports he received a grant from JSPS Overseas Research Fellowships. Bergmark reports he received grant support from Abbott Vascular, AstraZeneca and Pfizer and has received consulting fees from Abbott Vascular, Daiichi-Sankyo, Janssen, Philips, Quark and Servier. Please see the study for all other authors’ relevant financial disclosures. Ohman reports he received research grants from Abiomed and Cheisi USA and consulted for Abiomed, Cara Therapeutics, Chiesi USA, Cytokinetics, Imbria Pharmaceuticals, Otsuka Pharmaceuticals, Milestone Pharmaceuticals and XyloCor Therapeutics. Nanna reports no relevant financial disclosures.
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Evolocumab, a PCSK9 inhibitor, in addition to statin therapy for stable atherosclerotic CVD may lower risk for future revascularization with PCI or CABG, according to findings published in the Journal of the American College of Cardiology.

As Healio previously reported, in the main results of the FOURIER trial, LDL lowering to a median of 30 mg/dL with evolocumab (Repatha, Amgen) in ASCVD was associated with lower risk for CV events.

Any coronary revascularizations, complex PCIs or any complex revascularizations were reduced following treatment of ASCVD with evolocumab.

FOURIER was a randomized trial of evolocumab compared with placebo in 27,564 patients with stable ASCVD on statin therapy.

“This analysis from the FOURIER trial shows that adding evolocumab to statin therapy in patients with established ASCVD reduces the risk of developing complex coronary artery disease requiring revascularization, including complex PCI and CABG individually,” Kazuma Oyama, MD, PhD, clinical research fellow in the division of cardiovascular medicine at Brigham and Women’s Hospital, and colleagues wrote. “The benefits of evolocumab tended to increase over time and were consistent across key subgroups, including LDL-C concentration and high-intensity statin use at baseline.”

For this analysis, researchers studied the ability of evolocumab to reduce risk for complex coronary atherosclerosis requiring revascularization. Complex revascularization was a composite of complex PCI, defined as multivessel PCI, at least three stents, at least three lesions treated, bifurcation PCI and/or total stent length greater than 60 mm, or CABG.

Risk reduction with evolocumab

Overall, 1,724 patients underwent coronary revascularization, of which 37% were considered complex. Of these, 17% underwent CABG only; 19% underwent PCI only; and approximately 64% underwent both.

Researchers observed that among patients with stable ASCVD, evolocumab reduced the risk for:

  • any coronary revascularization by 22% (HR = 0.78; 95% CI, 0.71-0.86; P < .001);
  • simple PCI by 22% (HR = 0.78; 95% CI, 0.7-0.88; P < .001);
  • complex PCI by 33% (HR = 0.67; 95% CI, 0.54-0.84; P < .001);
  • CABG by 24% (HR = 0.76; 95% CI, 0.6-0.96; P = .019); and
  • complex revascularization by 29% (HR = 0.71; 95% CI, 0.61-0.84; P < .001).

Moreover, the magnitude of risk reduction for complex revascularization increased over time, from 20% in the first year (HR = 0.8; 95% CI, 0.64-0.99) to 36% in the second year (HR = 0.64; 95% CI, 0.49-0.84) and 41% beyond the second year (HR = 0.59; 95% CI, 0.37-0.96).

“The present findings further the understanding of the clinical impact of PCSK9 inhibition,” the researchers wrote. “The greatest reductions observed here with evolocumab were for the most complex revascularization procedures, indicating what appears to be a shift with evolocumab from more complex revascularization procedures toward simple PCI or no revascularization at all.”

According to the study, the association between evolocumab and reduced risk for coronary revascularization and complex revascularization was consistent across subgroups, including those based on age (P = .47), sex (P = .73), race (P = .69), diabetes (P = .26), prior coronary revascularization (P = .44), estimated glomerular filtration rate (P = .23), baseline LDL (P = .6) and statin intensity at baseline (P = .48).

Brian A. Bergmark

“While the FOURIER and ODYSSEY OUTCOMES trials demonstrated the important effects of PCSK9 inhibitors on MI and coronary revascularization events broadly, there has so far been no examination of the coronary anatomical complexity or atherosclerosis burden at the time of revascularization in these patients,” Brian A. Bergmark, MD, FACC, FSCAI, investigator in the TIMI study group and interventional cardiologist in the complex coronary and CTO program at Brigham and Women's Hospital, told Healio. “We observed that in this modern cohort of patients with established atherosclerosis there was a quite high degree of coronary complexity at the time of revascularization, with left main disease present in 12%, proximal LAD disease in 36%, at least one chronic total occlusion in 36% and in-stent restenosis in 27%.

“There are important limitations, of course, including having anatomical data only available for patients who underwent revascularization and relying on clinical documentation rather than core laboratory angiographic assessment,” Bergmark said in an interview. “It would be helpful moving forward to further understand which patients are most at risk for these types of revascularization events and who derives the most clinical benefit from medical intervention.”

‘Sooner is better’

“An intriguing finding by Oyama et al was that the degree of risk reduction for complex revascularization associated with PCSK9 inhibitor treatment increased as follow-up progressed,” E. Magnus Ohman, MD, and Michael G. Nanna, MD, MHS, interventional cardiologists at the Duke Clinical Research Institute, wrote in a related editorial. “Beyond 2 years of follow-up, the risk reduction associated with PCSK9 inhibitor use reached an impressive 41% decrease in complex revascularization. This coupled with the numerically lower PCI complication rate among those assigned to evolocumab ... suggests that a ‘sooner is better’ approach may be optimal for initiation of PCSK9 inhibitors, even potentially before PCI.

“We may have finally married aggressive lipid-lowering management with revascularization, where LDL-C < 70 mg/dL should be considered the ‘norm’ as soon as possible after the onset of ACS,” Ohman and Nanna wrote.

For more information:

Brian A. Bergmark, MD, FACC, FSCAI, can be reached at bbergmark@bwh.harvard.edu.

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