Abstract
Sabatine MS, Giugliano RP, Wiviott SD, et al. N Engl J Med 2015; 372: 1500–1509.
Inhibition of proprotein convertase subtilisin-kexin type 9 (PCSK9) is a novel strategy for LDL cholesterol (LDL-C) reduction, which has delivered promising results in phase 3 trials. In particular, marked reductions in LDL-C, but also triglycerides and lipoprotein(a), have been noted, even in patients already treated with statins. However, hard outcome data are likely to be required for these agents to achieve widespread acceptance.
This report analysed combined data from open label trials of evolocumab, a monoclonal antibody against PCSK9, and identified a significant reduction in cardiovascular events in the treatment arm (hazard ratio 0.47 vs. control group, P = 0.003) after 12 months of treatment. One point of potential concern was a higher incidence of neurocognitive adverse events (0.9% vs. 0.3%), although this was not related to extent of LDL-C reduction.
In summary, this (and another article from the same edition reporting similar results with a related agent) provides the first evidence that PCSK9 inhibition reduces cardiovascular events – a finding that has been expected but nevertheless required confirmation.