" Patients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI) with drug-eluting stents (DES) require optimized medical therapy to prevent recurrent cardiovascular events. This includes both antiplatelet and lipid-lowering strategies. For antiplatelet therapy, dual antiplatelet therapy (DAPT) comprising aspirin and a potent P2Y12 inhibitor (such as ticagrelor) for 12 months is the current standard of care. While this regimen is effective in reducing ischemic events, it significantly increases the risk of major bleeding. To mitigate this bleeding risk, DAPT de-escalation strategies have been proposed, including a ""discontinuation strategy"" (early aspirin cessation) and a ""switching strategy"" (switching to a less potent P2Y12 inhibitor). Although previous studies have individually shown the safety and efficacy of these de-escalation approaches compared to standard 12-month DAPT, no head-to-head randomized trial has directly compared the discontinuation strategy (ticagrelor monotherapy after 1 month) against the switching strategy (aspirin plus clopidogrel after 1 month). For lipid-lowering therapy, current guidelines recommend high-intensity statin monotherapy to achieve aggressive low-density lipoprotein cholesterol (LDL-C) targets (e.g., \< 55 or \< 70 mg/dL). However, adherence to high-intensity statins can be limited by concerns over adverse effects and poor patient compliance. In this context, a combination of moderate-intensity statin with ezetimibe has emerged as an alternative. While the previous trials have demonstrated non-inferiority of this combination strategy in a broad population with atherosclerotic cardiovascular disease, its efficacy and safety of initiating a moderate-intensity statin plus ezetimibe combination as the primary lipid-lowering therapy immediately after PCI for ACS remain to be established. The purpose of this investigation (OPACT trial) is to identify the optimal antiplatelet (OPACT-P) and lipid-lowering (OPACT-L) strategies for patients with ACS following DES implantation.
This is a prospective, open-label, multicenter, randomized, 2x2 factorial trial designed to evaluate the optimal antiplatelet and lipid-lowering strategies for patients with ACS following PCI with DES. Approximately 4,400 patients with ACS who have successfully undergone PCI with DES will be enrolled. Eligible patients will be randomized immediately after the index procedure in a 2x2 factorial design. This design allows for the simultaneous investigation of two separate primary objectives within the OPACT-P (antiplatelet) and OPACT-L (lipid-lowering) trials. The OPACT-P (antiplatelet) trial will investigate the safety and efficacy of two different DAPT de-escalation strategies. After an initial 1-month period of DAPT with aspirin and ticagrelor, patients will be randomized 1:1 to either: 1. A ""Discontinuation Strategy"": Ticagrelor (90 mg twice daily) monotherapy. 2. A ""Switching Strategy"": Aspirin (100 mg daily) plus clopidrel (75 mg daily). The primary objective of OPACT-P is to compare the incidence of major or clinically relevant non-major bleeding (defined as BARC type 2, 3, or 5) at 1 year between the two groups. A key secondary endpoint is the composite of major adverse cardiac and cerebrovascular events (MACCE) at 1 and 3 years. The OPACT-L (lipid-lowering) trial will compare the efficacy and safety of two lipid-lowering strategies, initiated immediately after PCI. Patients will be randomized 1:1 to either: 1. Combination Therapy: Moderate-intensity statin (Rosuvastatin 10 mg) plus Ezetimibe (10 mg). 2. Monotherapy: High-intensity statin (Rosuvastatin 20 mg). The primary endpoint of OPACT-L is the composite of all-cause death, spontaneous myocardial infarction, stroke, any coronary or peripheral revascularization, and hospitalization due to cardiovascular events at 3 years. All enrolled patients will be followed for a total of 3 years.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
4,400
* Month 0-1: Aspirin 100 mg qd + Ticagrelor 90 mg bid * Month 1-12: Ticagrelor 90 mg bid (Aspirin discontinued at 1 month) * Month 0-36: Rosuvastatin 10 mg qd + Ezetimibe 10 mg qd
* Month 0-1: Aspirin 100 mg qd + Ticagrelor 90 mg bid * Month 1-12: Aspirin 100 mg qd + Clopidogrel 75 mg qd (Switched at 1 month) * Month 0-36: Rosuvastatin 10 mg qd + Ezetimibe 10 mg qd * Drug : Rosuvastatin 10 mg + Ezetimibe 10 mg
* Month 0-1: Aspirin 100 mg qd + Ticagrelor 90 mg bid * Month 1-12: Ticagrelor 90 mg bid (Aspirin discontinued at 1 month) * Month 0-36: Rosuvastatin 20 mg qd
* Month 0-1: Aspirin 100 mg qd + Ticagrelor 90 mg bid * Month 1-12: Aspirin 100 mg qd + Clopidogrel 75 mg qd (Switched at 1 month) * Month 0-36: Rosuvastatin 20 mg qd * Drug : Rosuvastatin 20 mg
Division of Cardiology, Severance Cardiovascular Hospital Yonsei University College of Medicine, 250 Seongsanno, Seodaemun-gu 120-752 Seoul, South Korea
Seoul, South Korea
Major or Clinically-Relevant Non-Major Bleeding (OPACT-P)
Bleeding Academic Research Consortium (BARC) type 2, 3, or 5 bleeding
Time frame: Within 1 year after enrollment
Major Adverse Cardiac Events (OPACT-L)
A composite of all-cause death, spontaneous MI, stroke, coronary or peripheral revascularization, and hospitalization for cardiovascular events
Time frame: Within 3 years after enrollment
Key Secondray Outcomes for the OPACT-P trial
AA. MACCE (composite of all-cause death, spontaneous MI, stent thrombosis, stroke, or target-vessel revascularization) B. NACE: Major or clinically relevant non-major bleeding (BARC type 2, 3, 5) and MACCE C. BARC type 2 bleeding D. BARC type 3 bleeding E. BARC type 5 bleeding
Time frame: Withtin 1 and 3 years after enrollement
All-cause death (OPACT-P trial)
Number of participants who experienced all-cause death during the study period
Time frame: Withtin 1 and 3 years after enrollement
Cardiovascular death (OPACT-P trial)
Number of participants who experienced cardiovascular death during the study period
Time frame: Withtin 1 and 3 years after enrollement
Spontaneous MI (OPACT-P trial)
Number of participants who experienced spontaneous myocardial infarction during the study period
Time frame: Withtin 1 and 3 years after enrollement
Stroke (OPACT-P trial)
Number of participants who experienced stroke during the study period
Time frame: Withtin 3 years after enrollement
Target-vessel revascularization (OPACT-P trial)
Number of participants who underwent target-vessel revascularization during the study period
Time frame: Within 1 and 3 years after enrollment
Target-lesion revascularization (OPACT-P trial)
Number of participants who underwent target-lesion revascularization during the study period
Time frame: Within 1 and 3 years after enrollment
Definite or probable stent thrombosis (OPACT-P trial)
Number of participants who experienced definite or probable stent thrombosis during the study period
Time frame: Within 1 and 3 years after enrollment
Composite of all-cause death, spontaneous MI, or stroke (OPACT-P trial)
Number of participants who experienced the composite endpoint of all-cause death, spontaneous MI, or stroke
Time frame: Within 1 and 3 years after enrollment
Composite of cardiovascular death, spontaneous MI, or stent thrombosis (OPACT-P trial)
Number of participants who experienced the composite endpoint of cardiovascular death, spontaneous MI, or stent thrombosis
Time frame: Within 1 and 3 years after enrollment
Major or clinically relevant non-major bleeding - BARC type 2, 3, 5 (OPACT-P trial)
Number of participants who experienced major or clinically relevant non-major bleeding as defined by BARC type 2, 3, or 5 criteria
Time frame: Within 1 and 3 years after enrollment
Major or clinically relevant non-major bleeding - ISTH criteria (OPACT-P trial)
Number of participants who experienced major or clinically relevant non-major bleeding as defined by ISTH criteria
Time frame: Within 1 and 3 years after enrollment
Major or minor bleeding - TIMI criteria (OPACT-P trial)
Number of participants who experienced major or minor bleeding as defined by TIMI criteria
Time frame: Within 1 and 3 years after enrollment
Moderate, severe, or life-threatening bleeding - GUSTO criteria (OPACT-P trial)
Number of participants who experienced moderate, severe, or life-threatening bleeding as defined by GUSTO criteria
Time frame: Within 1 and 3 years after enrollment
Other prespecified analyses for the OPACT-P trial
A. Type of prescribed antiplatelet therapy B. Rate and reasons for non-adherence to the allocated treatment during study period
Time frame: Withtin 1 and 3 years after enrollement
All-cause death (OPACT-L trial)
Number of participants who experienced all-cause death during the study period
Time frame: Within 1 and 3 years after enrollment
Spontaneous MI (OPACT-L trial)
Number of participants who experienced spontaneous myocardial infarction during the study period
Time frame: Within 1 and 3 years after enrollment
Stroke (OPACT-L trial)
Number of participants who experienced stroke during the study period
Time frame: Within 1 and 3 years after enrollment
Coronary or peripheral revascularization (OPACT-L trial)
Number of participants who underwent coronary or peripheral revascularization during the study period
Time frame: Within 1 and 3 years after enrollment
Hospitalization for cardiovascular events (OPACT-L trial)
Number of participants who required hospitalization for cardiovascular events during the study period
Time frame: Within 1 and 3 years after enrollment
Composite of all-cause death, spontaneous MI, or stroke (OPACT-L trial)
Number of participants who experienced the composite endpoint of all-cause death, spontaneous MI, or stroke
Time frame: Within 1 and 3 years after enrollment
Composite of all-cause death, spontaneous MI, stent thrombosis, stroke, or TVR (OPACT-L trial)
Number of participants who experienced the composite endpoint of all-cause death, spontaneous MI, stent thrombosis, stroke, or target-vessel revascularization
Time frame: Within 1 and 3 years after enrollment
Composite of cardiovascular death, spontaneous MI, or TVR (OPACT-L trial)
Number of participants who experienced the composite endpoint of cardiovascular death, spontaneous MI, or target-vessel revascularization
Time frame: Within 1 and 3 years after enrollment
Treatment adherence for the OPACT-L trial
Proportion of participants with discontinuation or dose reduction of allocated lipid-lowering therapy during follow-up.
Time frame: Withtin 3 years after enrollement
Proportion of patients achieving LDL-C below 55 mg/dL (OPACT-L trial)
Proportion of participants achieving LDL cholesterol levels below 55 mg/dL during the study period
Time frame: Within 3 years after enrollment
Proportion of patients achieving LDL-C below 70 mg/dL (OPACT-L trial)
Proportion of participants achieving LDL cholesterol levels below 70 mg/dL during the study period
Time frame: Within 3 years after enrollment
LDL-C variability (OPACT-L trial)
LDL cholesterol variability (coefficient of variation) during the study period
Time frame: Within 3 years after enrollment
Number of participants with HbA1c increase 0.5% or more from baseline (OPACT-L trial)
Number of participants who experienced HbA1c increase of 0.5% or more from baseline during the study period
Time frame: Within 3 years after enrollment
Number of participants with CPK greater than 4x ULN (OPACT-L trial)
Number of participants who experienced creatine phosphokinase (CPK) elevation greater than 4 times the upper limit of normal during the study period
Time frame: Within 3 years after enrollment
Number of participants with AST or ALT 3x or more ULN (OPACT-L trial)
Number of participants who experienced AST and/or ALT elevation of 3 times or more the upper limit of normal during the study period
Time frame: Within 3 years after enrollment
Number of participants with serum creatinine increase greater than 50% from baseline (OPACT-L trial)
Number of participants who experienced serum creatinine increase greater than 50% from baseline during the study period
Time frame: Within 3 years after enrollment
Number of participants with statin-associated muscle symptom requiring intervention (OPACT-L trial)
Number of participants who experienced statin-associated muscle symptoms requiring intervention (dose reduction, discontinuation, or treatment) during the study period
Time frame: Within 3 years after enrollment
Number of participants with new-onset diabetes or diabetes requiring new medication (OPACT-L trial)
Number of participants who developed new-onset diabetes or required new anti-diabetic medication during the study period
Time frame: Within 3 years after enrollment
Number of participants who developed new-onset diabetes or required new anti-diabetic medication during the study period
Number of participants who underwent target-lesion revascularization during the study period
Time frame: Within 3 years after enrollment
Number of participants with target-vessel revascularization (OPACT-L trial)
Number of participants who underwent target-vessel revascularization during the study period
Time frame: Within 3 years after enrollment
Number of participants with new diagnosis of malignancy (OPACT-L trial)
Number of participants who were newly diagnosed with malignancy during the study period
Time frame: Within 3 years after enrollment
Number of participants with operation due to cataract (OPACT-L trial)
Number of participants who underwent cataract surgery during the study period
Time frame: Within 3 years after enrollment
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