No single RCT evaluating PCSK9 antibodies has yet been powered to show an effect on mortality and cardiovascular events. This analysis, which included 10,159 patients with a mean follow-up of 44.6 weeks, is the first to suggest a survival benefit associated with PCSK9 antibody treatment. Although preliminary, the authors say this finding is encouraging and further corroborated the observed similar direction of reduction in the odds of cardiovascular mortality (although this was not statistically significant).
The analysis is however limited by the use of study-level data; inclusion of studies that have not been fully published; the small number of clinical events (so clinical outcomes should be interpreted with caution); the short duration of follow-up; and the inclusion of studies evaluating different populations (studies focusing on particular populations will help refine knowledge about the groups that are most responsive to benefits with small risk for harm).
Ongoing trials should provide further data on the safety of this treatment strategy, and in particular should validate or refute the findings on mortality. Currently there are four large cardiovascular outcomes trials underway evaluating the effect of PCSK9 antibodies (evolocumab, alirocumab and bococizumab) on clinical outcomes; these are expected to complete in 2018.
No PCSK9 antibodies are currently approved in the EU.