Evolocumab in Patients with Cardiovascular Disease

CardiovascularOutcomes Research with PCSK9 Inhibition in Subjects with Elevated Risk (FOURIER) trial.The addition of evolocumab to standard therapy was associated with an absolute risk reduction of 2 percentage points in both the primary and secondary end points after a median duration of follow-up of 26 months.The fact that approximately 30% of the patients were receiving moderate-intensity statin therapy and the lack of clinical efficacy of evolocumab in the small group of patients receiving ezetimibe (presumably combined with a statin) arouse concern about the desirability of achieving such a marginal absolute risk reduction by inhibiting proprotein convertase subtilisin-kexin type 9 (PCSK9) in patients receiving high-intensity statin therapy, combined with ezetimibe, as appropriate.The results of trials that show a cardiovascular benefit of the addition of ezetimibe to statins 2,3 support the role of this combination as an initial lipid-lowering strategy in patients at high cardiovascular risk.Given the findings of the FOURIER trial, in patients at high cardiovascular risk in whom low-density lipoprotein (LDL) cholesterol goals cannot be achieved despite the use of lipid-lowering treatment, it would be more cost-effective to add evolocumab to a high-intensity statin combined with ezetimibe, as needed and if this combination has an acceptable side-effect profile.These recommendations are consistent with current guidelines that were published after PCSK9 inhibitors became available.