Early Single Antiplatelet Therapy After IVUS-Guided PCI in Acute Coronary Syndrome

Official title

Early Single Antiplatelet Therapy With a Potent P2Y12 Inhibitor After Intravascular Ultrasound-Guided PCI in Patients With Acute Coronary Syndrome: A Multicenter Randomized Controlled Trial

Overview

This is a prospective, open-label, multicenter, randomized, phase IV clinical trial designed to evaluate the safety and efficacy of early aspirin discontinuation followed by potent P2Y12 inhibitor monotherapy after intravascular ultrasound (IVUS)-guided drug-eluting stent implantation in patients with acute coronary syndrome. A total of 1,900 patients who achieve complete revascularization after IVUS-guided percutaneous coronary intervention (PCI) and meet the predefined successful IVUS-guided PCI criteria will be randomized in a 1:1 ratio to either the early single antiplatelet therapy group (Early SAPT: ticagrelor or prasugrel monotherapy) or the standard dual antiplatelet therapy group (Standard DAPT: aspirin plus ticagrelor or prasugrel). Randomization will be performed within 96 hours after completion of PCI, and clinical follow-up will be conducted at 1 month, 3 months, 6 months, and 12 months after randomization. The primary endpoints are major adverse cardiovascular events, defined as a composite of all-cause death, myocardial infarction, ischemia-driven target vessel revascularization, and definite or probable stent thrombosis occurring up to 12 months after randomization, and clinically relevant bleeding, defined as Bleeding Academic Research Consortium (BARC) type 2, 3, or 5 bleeding occurring up to 12 months after randomization. This study aims to determine whether early P2Y12 inhibitor monotherapy is non-inferior to standard dual antiplatelet therapy (DAPT) for ischemic events and is superior in reducing clinically relevant bleeding.

Detailed description

The study population will consist of patients diagnosed with acute coronary syndrome (ACS) who undergo percutaneous coronary intervention (PCI), achieve complete revascularization (CR) of all clinically significant coronary lesions under intravascular ultrasound (IVUS) guidance, and meet the imaging criteria predefined in this study.

Patients who meet all inclusion criteria and none of the exclusion criteria will be randomized within 96 hours after completion of PCI for CR, provided that no additional revascularization procedure is considered necessary. Before randomization, appropriate antiplatelet therapy including aspirin and a P2Y12 inhibitor may be administered according to the standard practice of each participating center. If staged PCI is planned, study enrollment and randomization will be allowed only after completion of all planned procedures. After the operator confirms successful procedural completeness based on final angiographic and IVUS images, eligible participants will be randomized in an open-label manner in a 1:1 ratio.

After randomization, the treatment strategy will be as follows. In the early single antiplatelet therapy (Early SAPT) group, aspirin will be discontinued immediately after randomization once CR has been confirmed, and potent P2Y12 inhibitor monotherapy will be administered as prasugrel 10 mg once daily or ticagrelor 90 mg twice daily. In the standard dual antiplatelet therapy (Standard DAPT) group, aspirin 100 mg once daily will be administered in combination with prasugrel 10 mg once daily or ticagrelor 90 mg twice daily. All patients will continue standard cardiovascular preventive therapy, including high-intensity statin therapy, beta-blockers, angiotensin-converting enzyme inhibitors (ACE inhibitors), or angiotensin receptor blockers (ARBs), as appropriate. A proton pump inhibitor (PPI) may be used at the discretion of the treating physician in patients at risk of gastrointestinal bleeding.

All randomized study participants will undergo clinical follow-up at 1 month, 3 months, 6 months, and 12 months after randomization.

Interventions

• Drug Early P2Y12 Inhibitor Monotherapy
  Participants randomized within 96 hours after successful IVUS-guided PCI will discontinue aspirin immediately after randomization and receive potent P2Y12 inhibitor monotherapy with ticagrelor 90 mg twice daily or prasugrel 10 mg once daily.
• Drug Standard Dual Antiplatelet Therapy
  Participants randomized within 96 hours after successful IVUS-guided PCI will receive aspirin 100 mg once daily plus a potent P2Y12 inhibitor, consisting of ticagrelor 90 mg twice daily or prasugrel 10 mg once daily, for 12 months.

Primary outcome measures

• Major Adverse Cardiovascular Events [Time frame: Up to 12 months after randomization]
• Clinically Relevant Bleeding [Time frame: Up to 12 months after randomization]

Secondary outcome measures (10)

• Incidence of Major and Minor Bleeding According to TIMI Criteria [Time frame: Up to 12 months after randomization]
• Incidence of Major and Minor Bleeding According to ISTH Criteria [Time frame: Up to 12 months after randomization]
• Incidence of All-Cause Death [Time frame: Up to 12 months after randomization]
• Incidence of Myocardial Infarction [Time frame: Up to 12 months after randomization]
• Incidence of Ischemia-Driven Target Vessel Revascularization [Time frame: Up to 12 months after randomization]
• Incidence of Definite or Probable Stent Thrombosis [Time frame: Up to 12 months after randomization]
• Incidence of Net Adverse Clinical Events [Time frame: Up to 12 months after randomization]
• All-Cause Rehospitalization Rate [Time frame: Up to 12 months after randomization]
• Medication Adherence [Time frame: Up to 12 months after randomization]
• Survival Rate at 12 Months [Time frame: At 12 months after randomization]

Eligibility criteria

Inclusion criteria

• Age >=18 years
• Diagnosis of acute coronary syndrome, including ST-segment elevation myocardial infarction (STEMI), non-ST-segment elevation myocardial infarction (NSTEMI), or unstable angina (UA)
• Successful IVUS-guided PCI with drug-eluting stent implantation
• Randomization within 96 hours after PCI
• Written informed consent

Exclusion criteria

• Planned staged PCI or CABG
• PCI failure, including no-reflow, major dissection, or thrombosis
• Need for oral anticoagulation
• Major bleeding within 30 days
• History of hemorrhagic stroke or ischemic stroke within 6 months
• Platelet count <100,000/mm3 or WBC count <3,000/mm3
• Contraindication to aspirin, ticagrelor, or prasugrel
• Life expectancy <1 year
• Current or potential pregnancy
• Investigator deems participation inappropriate

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

South Korea · 1 center

• Gyeongsang National University Hospital — Jinju

Publications

• Vrints C, Andreotti F, Koskinas KC, Rossello X, Adamo M, Ainslie J, Banning AP, Budaj A, Buechel RR, Chiariello GA, Chieffo A, Christodorescu RM, Deaton C, Doenst T, Jones HW, Kunadian V, Mehilli J, Milojevic M, Piek JJ, Pugliese F, Rubboli A, Semb AG, Senior R, Ten Berg JM, Van Belle E, Van Craenenbroeck EM, Vidal-Perez R, Winther S; ESC Scientific Document Group. 2024 ESC Guidelines for the mana PMID 39210710
• Guimaraes PO, Franken M, Tavares CAM, Antunes MO, Silveira FS, Andrade PB, Bergo RR, Joaquim RM, Tinoco de Paula JE, Nascimento BR, Pitta FG, Arruda JA, Serpa RG, Ohe LN, Mangione FM, Furtado RHM, Ferreira E, Sampaio FBA, T do Nascimento C, Genelhu LOO, Bezerra CG, Sarmento-Leite R, Maia LN, Oliveira FRA, Wainstein MV, Dall'Orto FTC, Monfardini F, Assis SRL, Nicolau JC, Sposito AC, Lopes RD, Onuma PMID 40888723
• Lee SY, Jeong YH, Yun KH, Cho JY, Gorog DA, Angiolillo DJ, Kim JW, Jang Y. P2Y12 Inhibitor Monotherapy Combined With Colchicine Following PCI in ACS Patients: The MACT Pilot Study. JACC Cardiovasc Interv. 2023 Aug 14;16(15):1845-1855. doi: 10.1016/j.jcin.2023.05.035. PMID 37587591
• Valgimigli M, Frigoli E, Heg D, Tijssen J, Juni P, Vranckx P, Ozaki Y, Morice MC, Chevalier B, Onuma Y, Windecker S, Tonino PAL, Roffi M, Lesiak M, Mahfoud F, Bartunek J, Hildick-Smith D, Colombo A, Stankovic G, Iniguez A, Schultz C, Kornowski R, Ong PJL, Alasnag M, Rodriguez AE, Moschovitis A, Laanmets P, Donahue M, Leonardi S, Smits PC; MASTER DAPT Investigators. Dual Antiplatelet Therapy after PMID 34449185
• Mehran R, Baber U, Sharma SK, Cohen DJ, Angiolillo DJ, Briguori C, Cha JY, Collier T, Dangas G, Dudek D, Dzavik V, Escaned J, Gil R, Gurbel P, Hamm CW, Henry T, Huber K, Kastrati A, Kaul U, Kornowski R, Krucoff M, Kunadian V, Marx SO, Mehta SR, Moliterno D, Ohman EM, Oldroyd K, Sardella G, Sartori S, Shlofmitz R, Steg PG, Weisz G, Witzenbichler B, Han YL, Pocock S, Gibson CM. Ticagrelor with or wi PMID 31556978
• Kim BK, Hong SJ, Cho YH, Yun KH, Kim YH, Suh Y, Cho JY, Her AY, Cho S, Jeon DW, Yoo SY, Cho DK, Hong BK, Kwon H, Ahn CM, Shin DH, Nam CM, Kim JS, Ko YG, Choi D, Hong MK, Jang Y; TICO Investigators. Effect of Ticagrelor Monotherapy vs Ticagrelor With Aspirin on Major Bleeding and Cardiovascular Events in Patients With Acute Coronary Syndrome: The TICO Randomized Clinical Trial. JAMA. 2020 Jun 16;32 PMID 32543684
• Vranckx P, Valgimigli M, Juni P, Hamm C, Steg PG, Heg D, van Es GA, McFadden EP, Onuma Y, van Meijeren C, Chichareon P, Benit E, Mollmann H, Janssens L, Ferrario M, Moschovitis A, Zurakowski A, Dominici M, Van Geuns RJ, Huber K, Slagboom T, Serruys PW, Windecker S; GLOBAL LEADERS Investigators. Ticagrelor plus aspirin for 1 month, followed by ticagrelor monotherapy for 23 months vs aspirin plus cl PMID 30166073
• Hahn JY, Song YB, Oh JH, Chun WJ, Park YH, Jang WJ, Im ES, Jeong JO, Cho BR, Oh SK, Yun KH, Cho DK, Lee JY, Koh YY, Bae JW, Choi JW, Lee WS, Yoon HJ, Lee SU, Cho JH, Choi WG, Rha SW, Lee JM, Park TK, Yang JH, Choi JH, Choi SH, Lee SH, Gwon HC; SMART-CHOICE Investigators. Effect of P2Y12 Inhibitor Monotherapy vs Dual Antiplatelet Therapy on Cardiovascular Events in Patients Undergoing Percutaneous PMID 31237645

Identifiers

NCT: NCT07684742 · SAPT-ACS

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗