The addition of evolocumab to a statin regimen was found to lower the risk for complex coronary disease requiring revascularization in patients with stable atherosclerosis, according to study results published in the Journal of the American College of Cardiology.
Evolocumab is an inhibitor of proprotein convertase subtilisin/kexin type 9 (PCSK9).
In the Further Cardiovascular Outcomes Research With PCSK9 Inhibition in Subjects With Elevated Risk (FOURIER; ClinicalTrials.gov Identifier: NCT01764633) trial, 27,564 patients (ages, 40-85 years) with atherosclerosis, prior myocardial infarction (MI), non-hemorrhagic stroke, or symptomatic peripheral artery disease (PAD) were enrolled. All participants had levels of low-density lipoprotein cholesterol ≥70 mg/dL or non–high-density lipoprotein cholesterol ≥100 mg/dL and were taking high or moderate intensity statin therapy with or without ezetimibe.
Participants were randomly assigned to receive 140 mg evolocumab every 2 weeks, 420 mg evolocumab once per month, or placebo. Clinical documentation of revascularization events was reviewed. Complex revascularization in this study was defined as a composite of complex percutaneous coronary intervention (PCI) or coronary artery bypass grafting surgery (CABG).
Over a median follow-up period of 2.2 years, 1724 patients underwent coronary revascularization, including PCI (n=1482), CABG (n=296), or both (n=54). A total of 632 patients (37%) underwent complex revascularization.
Treatment with evolocumab was associated with a 22% reduction in the risk for any coronary revascularization (hazard ratio [HR], 0.78; 95% CI, 0.70-0.88; P <.001). In participants treated with evolocumab, significant reductions in the risk for any coronary revascularization were also observed with simple PCI (22%; HR, 0.78; 95% CI, 0.70-0.88; P <.001), complex PCI (33%; HR, 0.67; 0.54-0.84; P <.001), CABG (24%; HR, 0.76; 95% CI, 0.60-0.96; P =.019), and complex revascularization (29%; HR, 0.71; 95% CI, 0.61-0.84; P <.001).
The magnitude of the relative risk reduction with regard to complex revascularization increased over time from 20% in the first year (HR, 0.80; 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).
Limitations of the study include the lack of baseline granular coronary artery anatomic information.
”[V]ery aggressive LDL-C lowering may have beneficial effects on coronary atherosclerosis burden, anatomical complexity, and the need for coronary revascularization,” concluded the study authors.
Disclosure: This clinical trial was supported by Amgen. Several study authors declared affiliations with the pharmaceutical industry. Please see the original reference for a full list of authors’ disclosures.
Oyama K, Furtado RHM, Fagundes A, et al. Effect of evolocumab on complex coronary disease requiring revascularization. J Am Coll Cardiol. Published online November 13, 2020. doi:10.1016/j.jacc.2020.11.011