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

Official title

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

Overview

" 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

• 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
• 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
• 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
• 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

Primary outcome measures

• Major or Clinically-Relevant Non-Major Bleeding (OPACT-P) [Time frame: Within 1 year after enrollment]
• Major Adverse Cardiac Events (OPACT-L) [Time frame: Within 3 years after enrollment]

Secondary outcome measures (12)

• Key Secondray Outcomes for the OPACT-P trial [Time frame: Withtin 1 and 3 years after enrollement]
• All-cause death (OPACT-P trial) [Time frame: Withtin 1 and 3 years after enrollement]
• Cardiovascular death (OPACT-P trial) [Time frame: Withtin 1 and 3 years after enrollement]
• Spontaneous MI (OPACT-P trial) [Time frame: Withtin 1 and 3 years after enrollement]
• Stroke (OPACT-P trial) [Time frame: Withtin 3 years after enrollement]
• Target-vessel revascularization (OPACT-P trial) [Time frame: Within 1 and 3 years after enrollment]
• Target-lesion revascularization (OPACT-P trial) [Time frame: Within 1 and 3 years after enrollment]
• Definite or probable stent thrombosis (OPACT-P trial) [Time frame: Within 1 and 3 years after enrollment]
• Composite of all-cause death, spontaneous MI, or stroke (OPACT-P trial) [Time frame: Within 1 and 3 years after enrollment]
• Composite of cardiovascular death, spontaneous MI, or stent thrombosis (OPACT-P trial) [Time frame: Within 1 and 3 years after enrollment]
• Major or clinically relevant non-major bleeding - BARC type 2, 3, 5 (OPACT-P trial) [Time frame: Within 1 and 3 years after enrollment]
• Major or clinically relevant non-major bleeding - ISTH criteria (OPACT-P trial) [Time frame: Within 1 and 3 years after enrollment]

Eligibility criteria

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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

South Korea · 1 center

• Division of Cardiology, Severance Cardiovascular Hospital Yonsei University College of Med — Seoul

Identifiers

NCT: NCT07432516 · 4-2025-0558

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗