Coronary Artery Disease
Conditions
Keywords
percutaneous coronary intervention
Brief summary
" 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.
Detailed description
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.
Interventions
DRUGDiscontinuation strategy + Combination lipid-lowering therapy
* 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
DRUGSwitching strategy + Combination lipid-lowering therapy
* 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
DRUGDiscontinuation strategy + High-intensity statin therapy
* 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
DRUGSwitching strategy + High-intensity statin therapy
* 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
Sponsors
Yonsei University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
19 Years to 85 Years
Healthy volunteers
No
Inclusion criteria
* Patients aged 19-85 years * Patients who received DES implantation for treating ACS, including unstable angina, non-ST elevation MI, and ST-elevation MI * Provision of informed consent
Exclusion criteria
* Requirement of oral anticoagulant therapy * Life expectancy \<3 years * Pregnancy or having plan for pregnancy * Patients with a history of serious adverse events or hypersensitivity to statins * Patients currently taking drugs that strongly interact with statins (such as cytochrome P-450 3A4 or 2C9 inhibitors) * Patients with risk factors for myopathy or rhabdomyolysis, such as hereditary muscle disorders, hypothyroidism, alcoholism, and severe liver dysfunction (\> 3x UNL) * Patients who refuse or cannot understand consent to participate in the clinical trial
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Major or Clinically-Relevant Non-Major Bleeding (OPACT-P) | Within 1 year after enrollment | Bleeding Academic Research Consortium (BARC) type 2, 3, or 5 bleeding |
| Major Adverse Cardiac Events (OPACT-L) | Within 3 years after enrollment | A composite of all-cause death, spontaneous MI, stroke, coronary or peripheral revascularization, and hospitalization for cardiovascular events |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Target-vessel revascularization (OPACT-P trial) | Within 1 and 3 years after enrollment | Number of participants who underwent target-vessel revascularization during the study period |
| Key Secondray Outcomes for the OPACT-P trial | Withtin 1 and 3 years after enrollement | 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 |
| All-cause death (OPACT-P trial) | Withtin 1 and 3 years after enrollement | Number of participants who experienced all-cause death during the study period |
| Cardiovascular death (OPACT-P trial) | Withtin 1 and 3 years after enrollement | Number of participants who experienced cardiovascular death during the study period |
| Target-lesion revascularization (OPACT-P trial) | Within 1 and 3 years after enrollment | Number of participants who underwent target-lesion revascularization during the study period |
| Definite or probable stent thrombosis (OPACT-P trial) | Within 1 and 3 years after enrollment | Number of participants who experienced definite or probable stent thrombosis during the study period |
| Composite of all-cause death, spontaneous MI, or stroke (OPACT-P trial) | Within 1 and 3 years after enrollment | Number of participants who experienced the composite endpoint of all-cause death, spontaneous MI, or stroke |
| Composite of cardiovascular death, spontaneous MI, or stent thrombosis (OPACT-P trial) | Within 1 and 3 years after enrollment | Number of participants who experienced the composite endpoint of cardiovascular death, spontaneous MI, or stent thrombosis |
| Major or clinically relevant non-major bleeding - BARC type 2, 3, 5 (OPACT-P trial) | Within 1 and 3 years after enrollment | Number of participants who experienced major or clinically relevant non-major bleeding as defined by BARC type 2, 3, or 5 criteria |
| Major or clinically relevant non-major bleeding - ISTH criteria (OPACT-P trial) | Within 1 and 3 years after enrollment | Number of participants who experienced major or clinically relevant non-major bleeding as defined by ISTH criteria |
| Major or minor bleeding - TIMI criteria (OPACT-P trial) | Within 1 and 3 years after enrollment | Number of participants who experienced major or minor bleeding as defined by TIMI criteria |
| Moderate, severe, or life-threatening bleeding - GUSTO criteria (OPACT-P trial) | Within 1 and 3 years after enrollment | Number of participants who experienced moderate, severe, or life-threatening bleeding as defined by GUSTO criteria |
| Other prespecified analyses for the OPACT-P trial | Withtin 1 and 3 years after enrollement | A. Type of prescribed antiplatelet therapy B. Rate and reasons for non-adherence to the allocated treatment during study period |
| All-cause death (OPACT-L trial) | Within 1 and 3 years after enrollment | Number of participants who experienced all-cause death during the study period |
| Spontaneous MI (OPACT-L trial) | Within 1 and 3 years after enrollment | Number of participants who experienced spontaneous myocardial infarction during the study period |
| Stroke (OPACT-L trial) | Within 1 and 3 years after enrollment | Number of participants who experienced stroke during the study period |
| Coronary or peripheral revascularization (OPACT-L trial) | Within 1 and 3 years after enrollment | Number of participants who underwent coronary or peripheral revascularization during the study period |
| Hospitalization for cardiovascular events (OPACT-L trial) | Within 1 and 3 years after enrollment | Number of participants who required hospitalization for cardiovascular events during the study period |
| Composite of all-cause death, spontaneous MI, or stroke (OPACT-L trial) | Within 1 and 3 years after enrollment | Number of participants who experienced the composite endpoint of all-cause death, spontaneous MI, or stroke |
| Composite of all-cause death, spontaneous MI, stent thrombosis, stroke, or TVR (OPACT-L trial) | Within 1 and 3 years after enrollment | Number of participants who experienced the composite endpoint of all-cause death, spontaneous MI, stent thrombosis, stroke, or target-vessel revascularization |
| Composite of cardiovascular death, spontaneous MI, or TVR (OPACT-L trial) | Within 1 and 3 years after enrollment | Number of participants who experienced the composite endpoint of cardiovascular death, spontaneous MI, or target-vessel revascularization |
| Treatment adherence for the OPACT-L trial | Withtin 3 years after enrollement | Proportion of participants with discontinuation or dose reduction of allocated lipid-lowering therapy during follow-up. |
| Proportion of patients achieving LDL-C below 55 mg/dL (OPACT-L trial) | Within 3 years after enrollment | Proportion of participants achieving LDL cholesterol levels below 55 mg/dL during the study period |
| Proportion of patients achieving LDL-C below 70 mg/dL (OPACT-L trial) | Within 3 years after enrollment | Proportion of participants achieving LDL cholesterol levels below 70 mg/dL during the study period |
| LDL-C variability (OPACT-L trial) | Within 3 years after enrollment | LDL cholesterol variability (coefficient of variation) during the study period |
| Number of participants with HbA1c increase 0.5% or more from baseline (OPACT-L trial) | Within 3 years after enrollment | Number of participants who experienced HbA1c increase of 0.5% or more from baseline during the study period |
| Number of participants with CPK greater than 4x ULN (OPACT-L trial) | Within 3 years after enrollment | Number of participants who experienced creatine phosphokinase (CPK) elevation greater than 4 times the upper limit of normal during the study period |
| Number of participants with AST or ALT 3x or more ULN (OPACT-L trial) | Within 3 years after enrollment | Number of participants who experienced AST and/or ALT elevation of 3 times or more the upper limit of normal during the study period |
| Number of participants with serum creatinine increase greater than 50% from baseline (OPACT-L trial) | Within 3 years after enrollment | Number of participants who experienced serum creatinine increase greater than 50% from baseline during the study period |
| Number of participants with statin-associated muscle symptom requiring intervention (OPACT-L trial) | Within 3 years after enrollment | Number of participants who experienced statin-associated muscle symptoms requiring intervention (dose reduction, discontinuation, or treatment) during the study period |
| Number of participants with new-onset diabetes or diabetes requiring new medication (OPACT-L trial) | 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 developed new-onset diabetes or required new anti-diabetic medication during the study period | Within 3 years after enrollment | Number of participants who underwent target-lesion revascularization during the study period |
| Number of participants with target-vessel revascularization (OPACT-L trial) | Within 3 years after enrollment | Number of participants who underwent target-vessel revascularization during the study period |
| Number of participants with new diagnosis of malignancy (OPACT-L trial) | Within 3 years after enrollment | Number of participants who were newly diagnosed with malignancy during the study period |
| Spontaneous MI (OPACT-P trial) | Withtin 1 and 3 years after enrollement | Number of participants who experienced spontaneous myocardial infarction during the study period |
| Number of participants with operation due to cataract (OPACT-L trial) | Within 3 years after enrollment | Number of participants who underwent cataract surgery during the study period |
| Stroke (OPACT-P trial) | Withtin 3 years after enrollement | Number of participants who experienced stroke during the study period |
Countries
South Korea
Outcome results
None listed