Intensive Cholesterol-Lowering Within 24 Hours of PCI Perioperative Period

Official title

INtensive Cholesterol-Lowering With recatIcimab combiNation in Emergency PCI for Acute Myocardial Infarction: A Randomized Controlled Trial

Overview

This project team is conducting a multicenter randomized controlled study, aiming to administer PCSK9 inhibitors subcutaneously as early as possible within 24 hours during the perioperative period of AMI (included \<24h STEMI and NSTEMI), and subsequently once every 12 weeks for a total of 6 months, followed by step-down therapy according to guideline-recommended lipid-lowering strategies based on LDL-C target levels. The study will evaluate changes in blood lipids and inflammatory markers during hospitalization and at follow-up visits at 1, 3, 6, 9, and 12 months, as well as the incidence of MACE events. Safety will also be assessed, including liver enzymes, kidney function, and other adverse reactions. Compared with conventional treatment, the study will test efficacy and ultimately clarify that early combined use of PCSK9 inhibitors during the perioperative period of AMI patients can safely and effectively reduce LDL-C, control systemic inflammatory responses, and improve the incidence of MACE events.

Detailed description

This study is a multicenter, prospective, randomized controlled trial, with the Second Affiliated Hospital of Nanchang University as the leading center and 80 sub-centers established. The enrollment period is from September 1, 2025, to August 30, 2027, with a follow-up of 1 year. A total of 2,442 patients who meet the inclusion criteria will be randomly assigned to: Group 1 (G1, experimental group): intensive lipid-lowering therapy within 24 hours during the perioperative period of AMI (standard treatment + PCSK9 inhibitors) for 6 months; Group 2 (G2, control group): standard lipid-lowing treatment (20 mg atorvastatin/10 mg rosuvastatin ± cholesterol absorption inhibitors). After 6 months, both groups will continue treatment according to guideline-recommended standard therapy.

Randomization method: All eligible patients entering the respective groups will be randomly obtained a random number. The maximum follow-up period is 1 year. Safety evaluation includes monitoring all adverse events (AEs), serious adverse events (SAEs), as well as regular monitoring of vital signs and clinical laboratory tests.

Each center will screen hospitalized AMI patients according to inclusion and exclusion criteria. Baseline data will be entered into the CRF form for the first time, including basic patient information, admission details, laboratory and instrument examinations, surgical procedure details, postoperative medications, and occurrence of adverse events during hospitalization. After discharge, follow-up visits will be conducted at 1 month, 3 months, 6 months, 9 months, and 1 year, inquiring about current health status and medication usage, and recording the occurrence of endpoint events and lipid levels in the follow-up section of the CRF.

Interventions

• Drug Recaticimab
  Recaticimab 450 mg once every 12 weeks. Group 1 (G1, experimental group): Intensive lipid-lowering therapy within 24 hours during the perioperative period of AMI (standard treatment + PCSK9 inhibitors), treatment for 6 months; Group 2 (G2, control group): standard treatment (antiplatelet drugs, 20 mg atorvastatin/10 mg rosuvastatin ± cholesterol absorption inhibitors). After 6 months, both groups continued with guideline-recommended conventional treatment.

Primary outcome measures

• MACE [Time frame: From enrollment to the end of treatment at 12 months]

Secondary outcome measures (10)

• LDL-C reduction absolute value [Time frame: From enrollment to the end of treatment at 12 months, and record the values for every 1, 3, 6, 9, and 12 months if possible.]
• LDL-C targets achieved rate [Time frame: From enrollment to the end of treatment at 12 months, and record the values for every 1, 3, 6, 9, and 12 months if possible]
• Changes in Lp (a) levels [Time frame: From enrollment to the end of treatment at 12 months, and record the values for every 1, 3, 6, 9, and 12 months if possible]
• Changes in the size of carotid plaques [Time frame: From baseline to the mid at 6 months and end of treatment at the 12 months]
• Observation indicators of safety [Time frame: From enrollment to the end of treatment at 1, 3, 6, 9 ,12 months.]
• The occurrence rate of MACE events in 6 months [Time frame: From enrollment to the end of treatment at 6 months.]
• Cardiac death [Time frame: From enrollment to the end of treatment at 6 months and 1 year]
• Non fatal myocardial infarction [Time frame: From enrollment to the end of treatment at 6 months and 1 year.]
• Non fatal stroke [Time frame: From enrollment to the end of treatment at 6 months and 1 year]
• Hospitalization due to unplanned unstable angina and coronary revascularization [Time frame: From enrollment to the end of treatment at 6 months and 1 year.]

Eligibility criteria

Inclusion criteria

• Age ≥18 years;
• Meet the definition of acute myocardial infarction according to the "2019 Guidelines for the Diagnosis and Treatment of Acute ST-Segment Elevation Myocardial Infarction", including STEMI and NSTEMI with onset <24 hours;
• Able to understand and voluntarily sign the informed consent form.

Exclusion criteria

• Severe mental disorders that prevent the expression of consent;
• Severe heart failure (Killip class III or IV) or cardiogenic shock;
• According to the investigator's judgment, the presence of significant other abnormal signs, laboratory findings, or clinical conditions (such as tumors, shock, liver or kidney failure, etc.) that make participation unsuitable;
• Investigator's judgment that the subject cannot complete long-term follow-up;
• Intolerance to statins or cholesterol absorption inhibitors;
• Intolerance to injections;
• Subjects who received PCSK9 inhibitor treatment or participated in other PCSK9 inhibitor studies within 4 months before randomization;
• Pregnant women.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

Center list to be confirmed — check the primary protocol.

Publications

• Byrne RA, Rossello X, Coughlan JJ, Barbato E, Berry C, Chieffo A, Claeys MJ, Dan GA, Dweck MR, Galbraith M, Gilard M, Hinterbuchner L, Jankowska EA, Juni P, Kimura T, Kunadian V, Leosdottir M, Lorusso R, Pedretti RFE, Rigopoulos AG, Rubini Gimenez M, Thiele H, Vranckx P, Wassmann S, Wenger NK, Ibanez B; ESC Scientific Document Group. 2023 ESC Guidelines for the management of acute coronary syndrom PMID 37622654
• Rao SV, O'Donoghue ML, Ruel M, Rab T, Tamis-Holland JE, Alexander JH, Baber U, Baker H, Cohen MG, Cruz-Ruiz M, Davis LL, de Lemos JA, DeWald TA, Elgendy IY, Feldman DN, Goyal A, Isiadinso I, Menon V, Morrow DA, Mukherjee D, Platz E, Promes SB, Sandner S, Sandoval Y, Schunder R, Shah B, Stopyra JP, Talbot AW, Taub PR, Williams MS. 2025 ACC/AHA/ACEP/NAEMSP/SCAI Guideline for the Management of Patien PMID 40014670
• Raber L, Ueki Y, Otsuka T, Losdat S, Haner JD, Lonborg J, Fahrni G, Iglesias JF, van Geuns RJ, Ondracek AS, Radu Juul Jensen MD, Zanchin C, Stortecky S, Spirk D, Siontis GCM, Saleh L, Matter CM, Daemen J, Mach F, Heg D, Windecker S, Engstrom T, Lang IM, Koskinas KC; PACMAN-AMI collaborators. Effect of Alirocumab Added to High-Intensity Statin Therapy on Coronary Atherosclerosis in Patients With Ac PMID 35368058
• Koskinas KC, Windecker S, Pedrazzini G, Mueller C, Cook S, Matter CM, Muller O, Haner J, Gencer B, Crljenica C, Amini P, Deckarm O, Iglesias JF, Raber L, Heg D, Mach F. Evolocumab for Early Reduction of LDL Cholesterol Levels in Patients With Acute Coronary Syndromes (EVOPACS). J Am Coll Cardiol. 2019 Nov 19;74(20):2452-2462. doi: 10.1016/j.jacc.2019.08.010. Epub 2019 Aug 31. PMID 31479722
• Ferri N, Ruscica M, Lupo MG, Vicenzi M, Sirtori CR, Corsini A. Pharmacological rationale for the very early treatment of acute coronary syndrome with monoclonal antibodies anti-PCSK9. Pharmacol Res. 2022 Oct;184:106439. doi: 10.1016/j.phrs.2022.106439. Epub 2022 Sep 12. PMID 36100012
• Cannon CP, Braunwald E, McCabe CH, Rader DJ, Rouleau JL, Belder R, Joyal SV, Hill KA, Pfeffer MA, Skene AM; Pravastatin or Atorvastatin Evaluation and Infection Therapy-Thrombolysis in Myocardial Infarction 22 Investigators. Intensive versus moderate lipid lowering with statins after acute coronary syndromes. N Engl J Med. 2004 Apr 8;350(15):1495-504. doi: 10.1056/NEJMoa040583. Epub 2004 Mar 8. PMID 15007110
• Schwartz GG, Olsson AG, Ezekowitz MD, Ganz P, Oliver MF, Waters D, Zeiher A, Chaitman BR, Leslie S, Stern T; Myocardial Ischemia Reduction with Aggressive Cholesterol Lowering (MIRACL) Study Investigators. Effects of atorvastatin on early recurrent ischemic events in acute coronary syndromes: the MIRACL study: a randomized controlled trial. JAMA. 2001 Apr 4;285(13):1711-8. doi: 10.1001/jama.285.13 PMID 11277825
• Patti G, Pasceri V, Colonna G, Miglionico M, Fischetti D, Sardella G, Montinaro A, Di Sciascio G. Atorvastatin pretreatment improves outcomes in patients with acute coronary syndromes undergoing early percutaneous coronary intervention: results of the ARMYDA-ACS randomized trial. J Am Coll Cardiol. 2007 Mar 27;49(12):1272-8. doi: 10.1016/j.jacc.2007.02.025. PMID 17394957

Identifiers

NCT: NCT07290699 · IIT-I-2025-098

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗