OPtimal Medical Strategy for Patients With Acute Coronary Syndrome Treated With Drug-eluting Stents: Enhancing Outcomes With antiPlatelet and Lipid-lowering Therapy (OPACT Trial)
试验速览
- 阶段
- 不适用
- 状态
- 尚未招募
- 入组人数
- 4,400
- 试验地点
- 1
- 主要终点
- Major or Clinically-Relevant Non-Major Bleeding (OPACT-P)
研究概览
简要总结
" 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.
详细描述
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:
- A ""Discontinuation Strategy"": Ticagrelor (90 mg twice daily) monotherapy.
- 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:
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 19 Years 至 85 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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
研究组 & 干预措施
Ticagrelor Monotherapy with Moderate-Intensity Statin/Ezetimibe
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.
干预措施: Discontinuation strategy + Combination lipid-lowering therapy (Drug)
Aspirin + Clopidogrel with Moderate-Intensity Statin/Ezetimibe
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.
干预措施: Switching strategy + Combination lipid-lowering therapy (Drug)
Ticagrelor Monotherapy with High-Intensity Statin Monotherapy
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.
干预措施: Discontinuation strategy + High-intensity statin therapy (Drug)
Aspirin + Clopidogrel with High-Intensity Statin Monotherapy
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.
干预措施: Switching strategy + High-intensity statin therapy (Drug)
结局指标
主要结局
Major or Clinically-Relevant Non-Major Bleeding (OPACT-P)
时间窗: Within 1 year after enrollment
Bleeding Academic Research Consortium (BARC) type 2, 3, or 5 bleeding
Major Adverse Cardiac Events (OPACT-L)
时间窗: Within 3 years after enrollment
A composite of all-cause death, spontaneous MI, stroke, coronary or peripheral revascularization, and hospitalization for cardiovascular events
次要结局
- Key Secondray Outcomes for the OPACT-P trial(Withtin 1 and 3 years after enrollement)
- All-cause death (OPACT-P trial)(Withtin 1 and 3 years after enrollement)
- Cardiovascular death (OPACT-P trial)(Withtin 1 and 3 years after enrollement)
- Spontaneous MI (OPACT-P trial)(Withtin 1 and 3 years after enrollement)
- Stroke (OPACT-P trial)(Withtin 3 years after enrollement)
- Target-vessel revascularization (OPACT-P trial)(Within 1 and 3 years after enrollment)
- Target-lesion revascularization (OPACT-P trial)(Within 1 and 3 years after enrollment)
- Definite or probable stent thrombosis (OPACT-P trial)(Within 1 and 3 years after enrollment)
- Composite of all-cause death, spontaneous MI, or stroke (OPACT-P trial)(Within 1 and 3 years after enrollment)
- Composite of cardiovascular death, spontaneous MI, or stent thrombosis (OPACT-P trial)(Within 1 and 3 years after enrollment)
- Major or clinically relevant non-major bleeding - BARC type 2, 3, 5 (OPACT-P trial)(Within 1 and 3 years after enrollment)
- Major or clinically relevant non-major bleeding - ISTH criteria (OPACT-P trial)(Within 1 and 3 years after enrollment)
- Major or minor bleeding - TIMI criteria (OPACT-P trial)(Within 1 and 3 years after enrollment)
- Moderate, severe, or life-threatening bleeding - GUSTO criteria (OPACT-P trial)(Within 1 and 3 years after enrollment)
- Other prespecified analyses for the OPACT-P trial(Withtin 1 and 3 years after enrollement)
- All-cause death (OPACT-L trial)(Within 1 and 3 years after enrollment)
- Spontaneous MI (OPACT-L trial)(Within 1 and 3 years after enrollment)
- Stroke (OPACT-L trial)(Within 1 and 3 years after enrollment)
- Coronary or peripheral revascularization (OPACT-L trial)(Within 1 and 3 years after enrollment)
- Hospitalization for cardiovascular events (OPACT-L trial)(Within 1 and 3 years after enrollment)
- Composite of all-cause death, spontaneous MI, or stroke (OPACT-L trial)(Within 1 and 3 years after enrollment)
- Composite of all-cause death, spontaneous MI, stent thrombosis, stroke, or TVR (OPACT-L trial)(Within 1 and 3 years after enrollment)
- Composite of cardiovascular death, spontaneous MI, or TVR (OPACT-L trial)(Within 1 and 3 years after enrollment)
- Treatment adherence for the OPACT-L trial(Withtin 3 years after enrollement)
- Proportion of patients achieving LDL-C below 55 mg/dL (OPACT-L trial)(Within 3 years after enrollment)
- Proportion of patients achieving LDL-C below 70 mg/dL (OPACT-L trial)(Within 3 years after enrollment)
- LDL-C variability (OPACT-L trial)(Within 3 years after enrollment)
- Number of participants with HbA1c increase 0.5% or more from baseline (OPACT-L trial)(Within 3 years after enrollment)
- Number of participants with CPK greater than 4x ULN (OPACT-L trial)(Within 3 years after enrollment)
- Number of participants with AST or ALT 3x or more ULN (OPACT-L trial)(Within 3 years after enrollment)
- Number of participants with serum creatinine increase greater than 50% from baseline (OPACT-L trial)(Within 3 years after enrollment)
- Number of participants with statin-associated muscle symptom requiring intervention (OPACT-L trial)(Within 3 years after enrollment)
- 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(Within 3 years after enrollment)
- Number of participants with target-vessel revascularization (OPACT-L trial)(Within 3 years after enrollment)
- Number of participants with new diagnosis of malignancy (OPACT-L trial)(Within 3 years after enrollment)
- Number of participants with operation due to cataract (OPACT-L trial)(Within 3 years after enrollment)