Evolocumab Associated with Reduced Risk for Complex Revascularization: FOURIER Analysis

Statins added to the PCSK9 inhibitor evolocumab were associated with a significant reduction in the risk for developing complex coronary disease that requires intervention, according to new research.

This landmark analysis of the Further Cardiovascular Outcomes Research with PCSK9 Inhibition in Patients with Elevated Risk (FOURIER) trial, published in the Journal of the American College of Cardiology, was a double-blind, placebo-controlled, randomized trial that included 27,564 patients with prior myocardial infarction, nonhemorrhagic stroke, or symptomatic peripheral artery disease.  All patients had LDL cholesterol levels  ≥70 mg/dL or HDL cholesterol ≥100 mg/dL and were taking moderate- to high-intensity statin therapy. The researchers included key exclusion criteria such as recent myocardial infarction or stroke within four weeks, planned or expected heart surgery or revascularization within three months, as well as others. Study patients randomly received either subcutaneous evolocumab (420 mg once per month or 140 mg bimonthly) or placebo. Patients were then followed out to 2.2 years. The primary endpoint of interest was complex revascularization (a composite of complex percutaneous coronary intervention [PCI], or coronary artery bypass graft surgery [CABG]).

According to the study results, more than 1,700 patients underwent coronary revascularization (1,482 underwent PCI, 296 underwent CABG, and 54 underwent both). Complex revascularization was used in 632 (37%) of patients. The risk of coronary revascularization was reduced (95% confidence interval for all) by evolocumab by 22% (HR=0.78; 0.71 to 0.86; P<0.001), simple PCI by 22% (HR=0.78; 0.70 to 0.88; P<0.001), complex PCI by 33% (HR=0.67; 0.54 to 0.84; P<0.001), CABG surgery by 24% (HR=0.76; 0.60 to 0.96; P=0.019), and complex revascularization by 29% (HR=0.71; 0.61 to 0.84; P<0.001). The magnitude, according to the authors, of the risk reduction benefit for complex revascularization tended to increase over time out to two years.

“Among patients with atherosclerotic cardiovascular disease, adding evolocumab to statin therapy reduced the risk of developing complex coronary artery disease requiring revascularization, including complex PCI and CABG individually,” the researchers wrote in their conclusion. “Together with prior coronary imaging findings, these data suggest that very aggressive LDL-C lowering may have beneficial effects on coronary atherosclerosis burden, anatomic complexity, and need for coronary revascularization.”

The added in their discussion that this data is potential practice-changing.

“The present findings further the understanding of the clinical impact of PCSK9 inhibition,” they wrote in their discussion. “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. Additionally, the degree of this benefit increased over time in the landmark analyses, indicating a progressively greater reduction in complex coronary disease requiring intervention with sustained, aggressive LDL-cholesterol-lowering therapy.”