In 2003, after the discovery of PCSK9 gain-of-function mutations in FH patients the first monoclonal antibodies against PCSK9 were tested in preclinical and clinical studies (including ODYSSEY LONG TERM, ODYSSEY OUTCOMES, and FOURIER) demonstrating efficacy in reducing LDL cholesterol plasma levels in patients (91). Here, PCSK9 is linked to familial hyperaldosteronism.