Effects of proprotein convertase subtilisin-kexin type 9 inhibitors on inflammatory and hemostatic parameters in post myocardial infarction patients

Abstract

Despite progress in treatment, elevated levels of low-density lipoprotein cholesterol (LDL-C) and lipoprotein (a) (Lp(a)), represent a significant part of the residual risk. Both are associated with inflammation and the coagulation fibrinolytic system. The purpose of our research was to evaluate the effect of proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i) on lipid parameters and indicators of inflammation, coagulation and fibrinolysis. We included 100 post myocardial infarction (MI) patients with insufficiently controlled LDL-C values despite the maximum dose of statin, and highly elevated Lp(a). Patients received alirocumab or evolocumab (150 mg sc or 140 mg sc every two weeks, respectively), or placebo for 6 months.In patients receiving PCSK9i, a significant decrease in total cholesterol (TC), LDL-C, triglycerides (TG) and Lp(a), and an increase in high density lipoprotein cholesterol (p < 0.001 for all) was found. Before treatment, the concentrations of TC, LDL-C and TG correlated with the concentrations of thrombin activatable fibrinolysis inhibitor (r = 0.41, p < 0.001; r = 0.353, p < 0.001; r = 0.311, p = 0.003, respectively), and plasminogen activator inhibitor-1 (r = 0.302, p = 0.007; r = 0.218, p = 0.049; r = 0.278; p = 0.013, respectively). The concentrations of TC and LDL-C correlated with overall fibrinolytic potential (r = −0.220, p = 0.034; r = −0.207, p = 0.047, respectively). The concentration of TG was related to the concentration of interleukin 6 (r = 0.290, p = 0.004) and interleukin 8 (r = 0.332, p = 0.001). No correlations between Lp(a) and inflammatory or hemostatic variables were found. No associations were found after treatment. Our results show that inflammatory cytokines and fibrinolytic parameters are related to LDL-C and not Lp(a) in post-MI patients before and with neither of them following PCSK9i treatment.The trial registration number: NCT04613167, Date of registration: November 3, 2020.