The FOURIER trial evaluating whether evolocumab (Repatha, Amgen) reduces the risk of cardiovascular events in patients with clinically evident atherosclerotic cardiovascular disease (ASCVD) has met its primary composite endpoint (cardiovascular death, non-fatal myocardial infarction (MI), non-fatal stroke, hospitalisation for unstable angina or coronary revascularisation) and the key secondary composite endpoint (cardiovascular death, non-fatal MI or non-fatal stroke). No new safety issues were observed.
The EBBINGHAUS cognitive function trial also conducted in FOURIER patients achieved its primary endpoint, too, demonstrating that evolocumab was non-inferior to placebo for the effect on cognitive function.
Detailed results from the evolocumab FOURIER outcomes trial and the evolocumab EBBINGHAUS cognitive function trial are to be presented at the American College of Cardiology (ACC) 66th Annual Scientific in Washington, USA.
“In the GLAGOV study, we demonstrated that evolocumab has an effect on atherosclerosis, the underlying cause of cardiovascular disease. These FOURIER results show unequivocally the connection between lowering low density lipid cholesterol with evolocumab and cardiovascular risk reduction, even in a population already treated with optimised statin therapy,” says Sean E Harper, executive vice president of Research and Development at Amgen.
FOURIER (Further Cardiovascular Outcomes Research with PCSK9 Inhibition in Subjects with Elevated Risk) is a multinational Phase 3 double-blind, randomised, placebo-controlled trial in approximately 27,500 patients who had either an MI, an ischaemic stroke or symptomatic peripheral artery disease and low density lipid count ≥70mg/dL or a non-high density lipid-C ≥100mg/dL on optimised statin therapy. Optimised statin therapy was defined as at least atorvastatin 20mg or equivalent daily with a recommendation for at least atorvastatin 40mg or equivalent daily where approved. Patients were randomised to receive evolocumab subcutaneous 140mg every two weeks or 420mg monthly or placebo subcutaneous every two weeks or monthly. The study continued until at least 1,630 patients experienced a key secondary MACE (major adverse cardiac event) endpoint of cardiovascular death, MI or stroke, whichever occurred first.
EBBINGHAUS (Evaluating PCSK9 Binding Antibody Influence On Cognitive Health in High Cardiovascular Risk Subjects) is a double-blind, placebo-controlled randomised non-inferiority trial involving approximately 1,900 patients enrolled in the FOURIER outcomes study. Executive function (Spatial Working Memory strategy index—primary endpoint) and secondary endpoints of working memory, memory function, and psychomotor speed were assessed using a tablet-based tool (CANTAB) at baseline and select time points.