Abstract
M Sabatine, R Giugliano, A Keech, et al. N Engl J Med. Epub ahead of print 17 March 2017. DOI: 10.1056/NEJMoa1615664.
Monoclonal antibodies directed against proprotein convertase subtilisin-kexin type 9 (PCSK9) are becoming established as highly efficacious agents for lowering low-density lipoprotein cholesterol (LDL-C). Evidence that they improve cardiovascular outcomes is, however, lacking. The FOURIER trial sought to investigate this by randomizing 27,525 patients with a history of cardiovascular disease to evolocumab or placebo as additional lipid-lowering therapy, for a median follow-up of 2.2 years. Active treatment reduced LDL-C by 59% and resulted in a 15% reduction in the composite primary endpoint (cardiovascular death, myocardial infarction, stroke, hospitalization for unstable angina, or coronary revascularization), and a 20% reduction in the secondary endpoint (cardiovascular death, myocardial infarction or stroke). Importantly, however, evolocumab had no observed effect on cardiovascular mortality when considered in isolation. Adverse events were infrequent, although injection-site reactions were more common with evolocumab. Subjects treated in this trial are not representative of those currently qualifying for PCSK9 inhibition in the UK based on recommendations by NICE, since the median pretreatment LDL-C was 2.4 mmol/L, and the minimum statin equivalent at trial entry was atorvastatin 20 mg daily. We await further trial evidence on the utility of this exciting class of drugs.