Impact of early PCSK9 inhibitor treatment on heart after percutaneous coronary intervention in patients with STEMI: Design and rationale of the PERFECT II trial

Abstract

Background and aimsPrimary percutaneous coronary intervention (PPCI) is the most effective treatment strategy for ST-segment elevation myocardial infarction (STEMI). Nevertheless, dysregulated inflammation induced by myocardial reperfusion injury may increase the final infarct size and induce maladaptive myocardial remodeling. Proprotein convertase subtilisin/kexin 9 (PCSK9) inhibitor, as a novel and potent lipid-lowering drug, plays an important role in inflammation. The aim of this study is to investigate whether the early application of PCSK9 inhibitor can increase the myocardial salvage index (MSI) and improve ventricular remodeling in patients with STEMI.DesignThe PERFECT II trial is a prospective, open-label, multicenter, randomized controlled study involving 160 patients with STEMI who are scheduled to undergo PPCI. The eligible patients will be divided into PCSK9 inhibitor group and control group via the interactive web response system, at a 1:1 ratio. In the PCSK9 inhibitor group, the PCSK9 inhibitor alirocumab at a dose of 75 mg will be subcutaneously injected immediately after PPCI and administered every 2 weeks thereafter for 3 months based on conventional treatment. In the control group, conventional treatment will be administered. The primary endpoint is MSI, as measured by cardiac magnetic resonance imaging (CMR) at 1 week after PPCI. The secondary endpoints are the peak time of creatine kinase (CK)-MB and troponin I (TnI)/TnT after PPCI; the postoperative fall time of the ST segment on electrocardiography (ECG); the rate of plasma low-density lipoprotein cholesterol (LDL-C) compliance (< 1.4 mmol/L and a reduction of >50% from baseline) at 1, 3, and 6 months after PPCI; infarct size and ejection fraction (EF) measured by CMR at 6 months after PPCI; the occurrence of major adverse cardiovascular event (MACE: a composite of cardiovascular death, non-fatal myocardial infarction, stent thrombosis, repeat revascularization, stroke, and heart failure needed to be hospitalized).ConclusionsThis is the first multicenter study to investigate the effect of early application of the PCSK9 inhibitor alirocumab on MSI in patients with STEMI undergoing PPCI. The findings will provide an opportunity to explore novel ideas and methods for the treatment of acute myocardial infarction.Trial registrationClinicalTrials.gov, identifier: NCT05292404.

PCSK9 inhibitor in acute ischemic stroke patient receiving mechanical thrombectomy: early outcomes and safety

“…We proposed two mechanisms for the beneficial effects of early PCSK9 inhibitor use during MT: (1) The inhibition of PCSK9 could potentially prevent vessel re-occlusion and reduce infarct size. This hypothesis is supported by findings from a pilot randomized trial that indicated a trend toward an increased myocardial salvage index with immediate administration of PCSK9 inhibitor following coronary intervention ( 15 ); (2) PCSK9 inhibitors might reduce the hemorrhagic transformation in the reperfused area, thereby leading to favorable functional outcomes, as evidenced by the lower incidence of sICH in evolocumab users in our study.…”

“…In animal models, application of alirocumab and the anti-PCSK9 AT04A vaccine have been shown to reduce vascular inflammation and atherosclerotic lesions ( 12 , 25 ). There are several recent or ongoing studies examining the early use of PCSK9 inhibitors in acute coronary syndrome patients undergoing percutaneous coronary intervention with anticipated extra-LDL reduction and other pleiotropic effects ( 15 , 26 , 27 ).…”

“…These pleiotropic effects of PCSK9 inhibitors have also observed in small human studies ( 11 , 13 ), with follow-up studies using IVUS showing regression of atherosclerotic plaques ( 14 ). Based on these insights, several recent and ongoing studies have been employing PCSK9 inhibitors early in the treatment process and off-label for patients with acute myocardial infarction who are receiving percutaneous coronary intervention ( 15 , 16 ).…”