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" 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:
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:
All enrolled patients will be followed for a total of 3 years.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Ticagrelor Monotherapy with Moderate-Intensity Statin/Ezetimibe | Experimental | After PCI for ACS with DES, patients start rosuvastatin 10 mg qd + ezetimibe 10 mg qd immediately and continue through 36 months. They receive aspirin 100 mg qd + ticagrelor 90 mg bid for 1 month, then discontinue aspirin and continue ticagrelor 90 mg bid through 12 months. |
|
| Aspirin + Clopidogrel with Moderate-Intensity Statin/Ezetimibe | Active Comparator | After PCI for ACS with DES, patients begin rosuvastatin 10 mg qd + ezetimibe 10 mg qd immediately and continue through 36 months. They receive aspirin 100 mg qd + ticagrelor 90 mg bid for 1 month, then switch to aspirin 100 mg qd + clopidogrel 75 mg qd through 12 months. |
|
| Ticagrelor Monotherapy with High-Intensity Statin Monotherapy | Active Comparator | After PCI for ACS with DES, patients initiate rosuvastatin 20 mg qd immediately and maintain it for up to 36 months. They receive aspirin 100 mg qd + ticagrelor 90 mg bid for 1 month, then discontinue aspirin and continue ticagrelor 90 mg bid through 12 months. |
|
| Aspirin + Clopidogrel with High-Intensity Statin Monotherapy | Active Comparator | After PCI for ACS with DES, patients initiate rosuvastatin 20 mg qd immediately and maintain it for up to 36 months. They receive aspirin 100 mg qd + ticagrelor 90 mg bid for 1 month, then switch to aspirin 100 mg qd + clopidogrel 75 mg qd through 12 months. |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Discontinuation strategy + Combination lipid-lowering therapy | Drug |
|
| Measure | Description | Time Frame |
|---|---|---|
| Major or Clinically-Relevant Non-Major Bleeding (OPACT-P) | Bleeding Academic Research Consortium (BARC) type 2, 3, or 5 bleeding | 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 | Within 3 years after enrollment |
| Measure | Description | Time Frame |
|---|---|---|
| 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 | Withtin 1 and 3 years after enrollement |
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Inclusion Criteria:
Exclusion Criteria:
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Division of Cardiology, Severance Cardiovascular Hospital Yonsei University College of Medicine, 250 Seongsanno, Seodaemun-gu 120-752 Seoul, South Korea | Seoul | South Korea |
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| Switching strategy + Combination lipid-lowering therapy | Drug |
|
|
| Discontinuation strategy + High-intensity statin therapy | Drug |
|
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| Switching strategy + High-intensity statin therapy | Drug |
|
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| All-cause death (OPACT-P trial) | Number of participants who experienced all-cause death during the study period | Withtin 1 and 3 years after enrollement |
| Cardiovascular death (OPACT-P trial) | Number of participants who experienced cardiovascular death during the study period | Withtin 1 and 3 years after enrollement |
| Spontaneous MI (OPACT-P trial) | Number of participants who experienced spontaneous myocardial infarction during the study period | Withtin 1 and 3 years after enrollement |
| Stroke (OPACT-P trial) | Number of participants who experienced stroke during the study period | Withtin 3 years after enrollement |
| Target-vessel revascularization (OPACT-P trial) | Number of participants who underwent target-vessel revascularization during the study period | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | Within 1 and 3 years after enrollment |
| Spontaneous MI (OPACT-L trial) | Number of participants who experienced spontaneous myocardial infarction during the study period | Within 1 and 3 years after enrollment |
| Stroke (OPACT-L trial) | Number of participants who experienced stroke during the study period | 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 | 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 | 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 | 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 | 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 | 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. | 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 | 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 | Within 3 years after enrollment |
| LDL-C variability (OPACT-L trial) | LDL cholesterol variability (coefficient of variation) during the study period | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | Within 3 years after enrollment |
| ID | Term |
|---|---|
| D003324 | Coronary Artery Disease |
| ID | Term |
|---|---|
| D003327 | Coronary Disease |
| D017202 | Myocardial Ischemia |
| D006331 | Heart Diseases |
| D002318 | Cardiovascular Diseases |
| D001161 | Arteriosclerosis |
| D001157 | Arterial Occlusive Diseases |
| D014652 | Vascular Diseases |
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