Acute Coronary Syndrome (ACS) Undergoing Percutaneous Coronary Intervention (PCI), Dual Anti-platelet Therapy
Conditions
Brief summary
This randomized controlled trial aims to evaluate the safety and efficacy of an aspirin-free strategy after 3-6 months of dual antiplatelet therapy (DAPT) in patients with acute coronary syndrome (ACS) who have undergone complete coronary revascularization by percutaneous coronary intervention (PCI). Participants will be randomized to either discontinue aspirin and continue P2Y12 inhibitor monotherapy or continue standard antiplatelet therapy. The primary objective is to determine whether the aspirin-free strategy reduces bleeding events without increasing ischemic events during follow-up.
Detailed description
Acute Coronary Syndrome (ACS) remains a leading cause of cardiovascular mortality and morbidity worldwide. Current management of ACS-including ST-segment elevation myocardial infarction (STEMI), non-ST-segment elevation myocardial infarction (NSTEMI), and high-risk unstable angina (UA)-relies on early invasive revascularization using Percutaneous Coronary Intervention (PCI) with contemporary Drug-Eluting Stents (DES). Following PCI, endothelial injury and stent implantation activate platelet aggregation and thrombosis, making Dual Antiplatelet Therapy (DAPT) with aspirin plus a P2Y12 inhibitor the standard treatment to prevent stent thrombosis and recurrent ischemic events. International guidelines have traditionally recommended 12 months of DAPT after ACS. However, prolonged DAPT increases the risk of bleeding, including gastrointestinal and intracranial hemorrhage, which is associated with higher mortality, treatment discontinuation, poor adherence, and increased healthcare utilization. To improve the balance between ischemic protection and bleeding risk, several landmark randomized trials-including TWILIGHT, TICO, STOPDAPT-2, STOPDAPT-3, SMART-CHOICE, and GLOBAL LEADERS-have investigated abbreviated DAPT followed by P2Y12 inhibitor monotherapy after 1-3 months of treatment. These studies consistently demonstrated a significant reduction in major bleeding without a corresponding increase in major ischemic outcomes, including myocardial infarction or stent thrombosis. Despite these promising findings, most available evidence has been generated in East Asian populations, where genetic factors, including CYP2C19 polymorphisms, and differences in thrombotic and bleeding risk may limit the generalizability of the results to other populations This clinical trial aims to address this important evidence gap by evaluating the safety and efficacy of abbreviated DAPT followed by P2Y12 inhibitor monotherapy in a non-Asian ACS population undergoing PCI with contemporary drug-eluting stents
Interventions
DRUGAspirin-Free Strategy
Aspirin will be discontinued after 3-6 months of dual antiplatelet therapy, and participants will continue P2Y12 inhibitor monotherapy for the remainder of the study follow-up
DRUGDual Antiplatelet Therapy
Participants will continue standard antiplatelet therapy according to current clinical practice after complete coronary revascularization.
Sponsors
Assiut University
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
NONE
Masking description
No masking (open-label). Participants and investigators will be aware of the assigned treatment. Allocation will be concealed using sequentially numbered, opaque, sealed envelopes.
Intervention model description
Participants with acute coronary syndrome who have undergone complete revascularization will be randomly assigned in a 1:1 ratio to either an aspirin-free strategy (discontinuation of aspirin after 3-6 months of dual antiplatelet therapy with continuation of P2Y12 inhibitor monotherapy) or continued standard antiplatelet therapy. Participants will be followed for ischemic and bleeding outcomes.
Eligibility
Sex/Gender
ALL
Healthy volunteers
Yes
Inclusion criteria
* 1\. Must have an established, objectively confirmed diagnosis of an acute coronary syndrome, classified as STEMI, NSTEMI, or high-risk Unstable Angina. 2\. Underwent successful PCI with deployment of contemporary drug-eluting stents (DES) and TIMI 3 flow. 3\. Achieved documented complete revascularization of all angiographically significant lesions during the index procedure. 4\. Maintained absolute adherence to standard, uncomplicated combination DAPT for exactly 30 ± 7 days following the index PCI, remaining completely free of any ischemic or bleeding events during this initial month. 5\. Patient is fully coherent, cooperative, able to comply with the mandated multi-month follow-up schedule, and has provided independent, written, personally signed informed consent prior to randomization.
Exclusion criteria
Left Main (LM) Coronary Artery Disease \& bifurcation lesions with 2 stents : Any angiographically documented significant stenosis (\>50% diameter stenosis) involving the unprotected left main coronary artery trunk, regardless of whether it was treated with a stent during the index procedure or left untreated. 2\. Incomplete Revascularization / Residual Target Lesions: Presence of any remaining untreated coronary lesion with \>50% diameter stenosis in any major epicardial vessel or branch with a reference vessel diameter ≥2.0 mm that requires, or is planned to require, any future surgical or percutaneous revascularization within the next 12 months. This 'other lesion' exclusion ensures a fully revascularized cohort. 3\. Any prior historical or documented acute, subacute, or late definitive stent thrombosis. 4\. High baseline ischemic features including end-stage chronic kidney disease (eGFR \< 30 mL/min/1.73m²), severe left ventricular dysfunction (LVEF \< 30%), or an un-revascularized multi-vessel burden with high residual SYNTAX score (\>22). 5\. Definitive clinical indication for continuous, long-term oral anticoagulation therapy (e.g., atrial fibrillation, mechanical valves, deep vein thrombosis, or pulmonary embolism). 6\. Active major pathological bleeding, history of any spontaneous or traumatic intracranial hemorrhage, vascular malformations of the central nervous system, or an established bleeding diathesis. 7\. Active system-wide infections, or documented chronic systemic inflammatory or autoimmune disorders (such as severe active rheumatoid arthritis, systemic lupus erythematosus, polymyalgia rheumatica, active inflammatory bowel disease), or active malignancies, which confound baseline leukocyte values. 8\. Known severe hypersensitivity, documented allergy, or major medical intolerance to acetylsalicylic acid (Aspirin) or clopidogrel (Plavix). \-
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Net adverse clinical events | 12 months | Composite of major adverse cardiovascular events (cardiovascular death, myocardial infarction, ischemic stroke, or definite/probable stent thrombosis) and major bleeding (BARC type 3 or 5). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Major Adverse Cardiovascular Events (MACE) | 12 months | Major Adverse Cardiac Events (MACE): A strict composite endpoint consisting of cardiovascular mortality, non-fatal myocardial infarction, or acute ischemic stroke. * Cardiovascular Mortality: Incorporates any death resulting from an acute myocardial infarction, sudden cardiac death, fatal cardiac arrest, cardiogenic shock, terminal heart failure, fatal stroke, or any death directly caused by a documented procedural complication related to the index or staged PCI. * Myocardial Infarction (MI): Diagnosed and classified in strict accordance with the Fourth Universal Definition of Myocardial Infarction (Type 1 spontaneous, Type 2 demand mismatch, Type 4a PCI-related). * Stent Thrombosis (ST): Formally categorized according to the Academic Research Consortium (ARC) consensus definitions into definite, probable, or possible stent thrombosis. Definite Stent Thrombosis requires unequivocal angiographic confirmation of a thrombus originating within or directly adjacent to the stented segment |
| Bleeding | 12 months | The primary safety outcome is the occurrence of bleeding complications, which will be characterized using the international Bleeding Academic Research Consortium (BARC) consensus |
Countries
Egypt
Contacts
CONTACTAsmaa Sayed Shaban, MBBch
Outcome results
None listed