Optimal Antiplatelet and Lipid Therapy in ACS With DES: OPACT Trial

OPtimal Medical Strategy for Patients With Acute Coronary Syndrome Treated With Drug-eluting Stents: Enhancing Outcomes With antiPlatelet and Lipid-lowering Therapy (OPACT Trial)

" 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.

Study Overview

• Status: Not yet recruiting
• Conditions: Coronary Artery Disease
• Intervention / Treatment: Drug: Discontinuation strategy + Combination lipid-lowering therapy; Drug: Switching strategy + Combination lipid-lowering therapy; Drug: Discontinuation strategy + High-intensity statin therapy; Drug: Switching strategy + High-intensity statin therapy

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.

• Study Type: Interventional
• Enrollment (Estimated): 4400
• Phase: Not Applicable

Contacts and Locations

Study Locations

• South Korea
  • Seoul, South Korea
    • Division of Cardiology, Severance Cardiovascular Hospital Yonsei University College of Medicine, 250 Seongsanno, Seodaemun-gu 120-752 Seoul, South Korea

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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.	Drug: Discontinuation 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
Active Comparator: 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.	Drug: Switching 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
Active Comparator: 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.	Drug: Discontinuation 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
Active Comparator: 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.	Drug: Switching 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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

Secondary Outcome Measures

Outcome Measure	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
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

Collaborators and Investigators

• Sponsor: Yonsei University

Study record dates

Study Major Dates

• Study Start (Estimated): February 1, 2026
• Primary Completion (Estimated): June 1, 2033
• Study Completion (Estimated): June 1, 2033

Study Registration Dates

• First Submitted: November 14, 2025
• First Submitted That Met QC Criteria: February 19, 2026
• First Posted (Actual): February 25, 2026

Study Record Updates

• Last Update Posted (Actual): February 25, 2026
• Last Update Submitted That Met QC Criteria: February 19, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Keywords: percutaneous coronary intervention
• Additional Relevant MeSH Terms: Vascular Diseases; Cardiovascular Diseases; Heart Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Coronary Disease; Myocardial Ischemia; Coronary Artery Disease
• Other Study ID Numbers: 4-2025-0558

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No