PCSK9 Inhibitor Evolocumab Study

USA: The PCSK9 inhibitor evolocumab significantly reduces the rate of major adverse cardiovascular events (MACEs) in patients with and without multivessel coronary artery disease (MVD), according to a new analysis of FOURIER and its open-label extension study. The findings were published online in the Journal of the American College of Cardiology.

"The magnitude of effect with evolocumab was about twice as large in those who had multivessel disease, benefit emerged early and grew larger over time in this higher-risk subgroup," the researchers reported.

"In those without MVD, the treatment effect was observed roughly after one year and did become larger during extended follow-up."

In the FOURIER, risk reduction for MACEs with evolocumab was greater in patients with multivessel disease, during a median follow-up of 2.2 years. The FOURIER Open-Label Extension (FOURIER-OLE) provides an additional median follow-up of 5 years.

Daniel J. McClintick, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts, USA, and colleagues aimed to assess the long-term benefit of evolocumab in patients with and without MVD.

FOURIER randomized 27,564 patients to evolocumab versus placebo; 6,635 entered FOURIER-OLE. Based on the presence of MVD (≥40% stenosis in ≥2 large vessels), patients with coronary artery disease (CAD) were categorized.

The new study included patients in FOURIER and FOURIER-OLE, the open-label extension study including those initially randomized to evolocumab continued on treatment as well as placebo-treated patients who switched to evolocumab. At the start of FOURIER, 6,007 had an MVD and 17,649 had CAD without multivessel disease.

The median follow-up of FOURIER was 2.2 years, but the 5,887 patients who entered FOURIER-OLE were followed for an additional 5.0 years. The median and maximum follow-up for the analysis were 7.1 and 8.6 years, respectively.

The primary endpoint of the study was myocardial infarction, cardiovascular death, stroke, hospitalization for unstable angina, or coronary revascularization. The key secondary endpoint was myocardial infarction, cardiovascular death, or stroke.

Key Findings

• Of 23,656 patients in FOURIER with CAD, 25.4% had MVD; 5,887 patients continued into FOURIER-OLE.
• The risk reduction with initial allocation to evolocumab tended to be greater in patients with MVD than in those without: 23% (HR: 0.77) versus 11% (HR: 0.89) for the primary and 31% (HR: 0.69) versus 15% (HR: 0.85) for the key secondary endpoints.
• The magnitude of benefit tended to grow during the first several years, reaching 37% to 38% reductions in risk in patients with MVD and 23% to 28% reductions in risk in patients without MVD.
• The findings showed a reduction in MACE rates with evolocumab in patients with and without MVD. The benefit tended to occur earlier and was larger in patients with MVD. However, in both groups, the magnitude grew over time.

"These data support early initiation of intensive low-density lipoprotein cholesterol lowering both in patients with and without multivessel disease," the researchers concluded.

Reference

McClintick DJ, O'Donoghue ML, De Ferrari GM, Ferreira J, Ran X, Im K, López JAG, Elliott-Davey M, Wang B, Monsalvo ML, Atar D, Keech A, Giugliano RP, Sabatine MS. Long-Term Efficacy of Evolocumab in Patients With or Without Multivessel Coronary Disease. J Am Coll Cardiol. 2024 Feb 13;83(6):652-664. doi: 10.1016/j.jacc.2023.11.029. PMID: 38325990.