Early versus delayed evolocumab treatment and complex coronary artery revascularization

In FOURIER, the PCSK9 inhibitor evolocumab (Evo) significantly reduced the rate of major adverse cardiovascular events and coronary revascularization.

To investigate the effect of evolocumab on the incidence of complex coronary revascularization during long-term follow-up.

In FOURIER, patients with atherosclerotic cardiovascular disease with LDL-C ≥70mg/dL despite optimized statin therapy were randomized to evolocumab or placebo. At the end of the trial, patients had the option to be treated with evolocumab in the open label extension (OLE) at participating sites. All cases of coronary revascularization were centrally reviewed, and complex revascularization was defined as coronary artery bypass graft surgery (CABG) or complex percutaneous coronary intervention (PCI) using the GLOBAL LEADERS definition. Event rates through 8 years were compared between patients randomized in the parent trial to evolocumab or placebo.

Of 27,564 patients in FOURIER, 6,635 patients (median achieved LDL-C 30 mg/dL) continued in OLE (total median follow-up 7.2 years). Patients initially randomized to evolocumab were treated on average 2.2 years earlier than patients starting treatment during OLE. In patients receiving evolocumab earlier, the rate for complex coronary revascularization through 8 years was reduced by 24% (HR 0.76 [0.67, 0.87], p<0.001). This effect was consistent for both CABG (HR 0.77 [0.66, 0.94], p=0.01) and complex PCI (HR 0.78 [0.65, 0.93], p=0.006) individually. Early versus delayed evolocumab therapy resulted in lower total stent length implanted (22,521 mm vs 28,946 mm, p<0.001).

Compared with delayed treatment initiation, early and sustained treatment with evolocumab significantly reduced the likelihood of complex revascularization during long-term follow-up.