Evolocumab in STEMI

The gold standard for the treatment of ST-segment elevation myocardial infarction (STEMI) is to rapidly restore myocardial blood flow through primary percutaneous coronary intervention (primary PCI) as soon as possible. While primary PCI achieves successful reperfusion of the infarct-related epicardial coronary artery in over 90% of these patients, only approximately 35% achieve ideal reperfusion to the myocardium level. This condition is termed myocardial no-reflow or microvascular obstruction (MVO). The primary pathophysiology of MVO includes severe inflammatory reactions within the ischemic vessel, distal embolization of thrombi, microthrombi formation in the microvasculature, and microvascular spasm, tissue peri-infarct edema, and intramyocardial hemorrhage. Previous studies has reported that the use of atorvastatin 80mg before PCI can reduce myocardial injury occurring during PCI in patients with acute coronary syndrome (ACS), and can improve microvascular blood flow in STEMI patients undergoing primary PCI. Furthermore, it has been reported to improve microvascular functional impairment evaluated by microvascular resistance index in non-ST-segment elevation acute coronary syndrome patients and exhibit anti-inflammatory effects. However, Two randomized trials atorvastatin 80mg did not reduce infarct size, which was primary endpoint in STEMI patients.

Recently, strong LDL cholesterol-lowering agent, PCSK9 inhibitors, have been developed and used in clinical practice, and they seem to have pleiotropic effects similar to high-intensity statins, including anti-inflammatory and antithrombotic effects. In-vitro and vivo models have shown that the introduction of human PCSK9 increases platelet aggregation in normal adult plasma and that mice without PCSK9 exhibit decreased arterial thrombosis and thrombus stability when induced . Patients with higher levels of serum PCSK9 had higher platelet reactivity after antiplatelet therapy and an increased incidence of ischemic events following coronary intervention in ACS setting. This suggests that circulating PCSK9 contributes to arterial thrombus formation, and PCSK9 inhibition may improve this. Additionally, evolocumab is known to reduce Lp(a), which is well-known for its pro-atherosclerotic and pro-inflammatory effects, by approximately 30%.

Also, Pharmaceutically, evolocumab exhibits maximum inhibitory effect against PCSK9 within just 4 hours of injection, potentially beneficial for patients with acute myocardial infarction who need a rapid effect before the infarction fully develops.

In this clinical trial, we hypothesize that administering evolocumab before primary PCI in patients with acute STEMI may reduce MVO through its antiplatelet and anti-inflammatory effects and subsequently decrease the size of the myocardial infarction.