Plasma kinetics of mature PCSK9, furin-cleaved PCSK9, and Lp(a) with or without administration of PCSK9 inhibitors in acute myocardial infarction.

Abstract Background There are two types of circulating proprotein convertase subtilisin/kexin type 9 (PCSK9), mature and furin-cleaved. Most types of lipoprotein(a) [Lp(a)], an independent risk factor of cardiovascular events, bind to mature PCSK9. Objective This study examined the effects of monoclonal anti-PCSK9 antibody on plasma PCSK9 and Lp(a) levels in acute myocardial infarction (MI). Methods Acute MI patients (n = 36) were randomly divided into evolocumab (140 mg; n = 17) and non-evolocumab (n = 19) groups. Changes in plasma PCSK9 and Lp(a) levels were monitored before and 1, 3, 5, 10, and 20 days after evolocumab administration. Results In the non-evolocumab group, plasma levels of mature PCSK9, furin-cleaved PCSK9, and Lp(a) (236.4 ± 57.3 ng/mL, 22.4 ± 5.8 ng/mL, and 19.2. ± 16.5 mg/dL, respectively) significantly increased by day 3 (408.8 ± 77.1 ng/mL, p  1000 ng/mL with a simultaneous decline of furin-cleaved PCSK9 below the measurement sensitivity level after day 3. The incremental area under the curve for plasma Lp(a) levels was significantly smaller in the evolocumab group compared with the non-evolocumab group (p = 0.038). Conclusion Mature and furin-cleaved PCSK9 are transiently upregulated after MI onset. Evolocumab significantly increases mature PCSK9 and decreases furin-cleaved PCSK9 and might inhibit transient increase of plasma Lp(a) in acute MI.