Assessment of Quitting Versus Using Aspirin Therapy In Patients Treated With Oral Anticoagulation for Atrial Fibrillation or Other Indication With Stabilized Coronary Artery Disease

* Long-term aspirin (ASA) is the standard recommended antithrombotic therapy in patients with stable coronary artery disease (CAD), especially following stenting (Class I, Level A). * Long-term oral anticoagulation (OAC) is the standard antithrombotic therapy in patients with atrial fibrillation (AF) associated with one or more risk factor for stroke (Class I, Level A). * During the first year following acute coronary syndrome (ACS) and/or percutaneous coronary intervention (PCI), several studies evaluating the combination of OAC treatment and antiplatelet therapy are either already published or ongoing. * At distance of the index ACS and/or PCI, patients with stable CAD and concomitant AF remain at particular high-risk of ischemic (3 to 4 times higher as compared to patients with stable CAD without AF) and bleeding events. Antithrombotic management of these patients is subsequently highly challenging in clinical practice. The European task force suggests that the use of a full-dose anticoagulant monotherapy without any antiplatelet therapy should be the default strategy in such patients with both, AF and stable CAD. * However, evidences are sparse and weak to support such a strategy (only observational studies with many biases) and no randomized trial has assessed this question. These patients, especially those at high-risk of recurrent ischemic events (post- ACS, diabetes, multivessel CAD…) may benefit from the combination of OAC and aspirin at long-term. Indeed the crude event rate of ischemic events is much higher than the crude event rate of bleeding in this specific population. Ischemic events are 2 to 3 times more frequent than bleeding in daily practice. * The benefit/risk ratio of these two different strategies (ASA in combination with OAC vs. OAC alone) in patients at high-risk of recurrent coronary and vascular events remains unknown. Dual therapy with full-dose anticoagulation and ASA may lead to higher risk of major bleeding, while stopping ASA in stabilized high-risk patients after PCI may lead to poorer outcome regarding ischemic events. * The coordinating investigators therefore designed a double blind placebo controlled trial in order to assess the optimal antithrombotic regimen that should be pursued long-life in this subset of patients.

* Long-term aspirin (ASA) is the standard recommended antithrombotic therapy in patients with stable coronary artery disease (CAD), especially following stenting (Class I, Level A). * Long-term oral anticoagulation (OAC) is the standard antithrombotic therapy in patients with atrial fibrillation (AF) associated with one or more risk factor for stroke (Class I, Level A). * During the first year following acute coronary syndrome (ACS) and/or percutaneous coronary intervention (PCI), several studies evaluating the combination of OAC treatment and antiplatelet therapy are either already published or ongoing. * At distance of the index ACS and/or PCI, patients with stable CAD and concomitant AF remain at particular high-risk of ischemic (3 to 4 times higher as compared to patients with stable CAD without AF) and bleeding events. Antithrombotic management of these patients is subsequently highly challenging in clinical practice. The European task force suggests that the use of a full-dose anticoagulant monotherapy without any antiplatelet therapy should be the default strategy in such patients with both, AF and stable CAD. * However, evidences are sparse and weak to support such a strategy (only observational studies with many biases) and no randomized trial has assessed this question. These patients, especially those at high-risk of recurrent ischemic events (post- ACS, diabetes, multivessel CAD…) may benefit from the combination of OAC and aspirin at long-term. Indeed the crude event rate of ischemic events is much higher than the crude event rate of bleeding in this specific population. Ischemic events are 2 to 3 times more frequent than bleeding in daily practice. * The benefit/risk ratio of these two different strategies (ASA in combination with OAC vs. OAC alone) in patients at high-risk of recurrent coronary and vascular events remains unknown. Dual therapy with full-dose anticoagulation and ASA may lead to higher risk of major bleeding, while stopping ASA in stabilized high-risk patients after PCI may lead to poorer outcome regarding ischemic events. AQUATIC is a prospective, randomized, double-blind, placebo controlled, parallel-group, multi-center study. Randomization into 2 treatment groups and stratified on study center, type of OAC (VKA vs. DOAC), antithrombotic treatment received at the time of inclusion (dual therapy combining single antiplatelet therapy + OAC vs. OAC alone). Experimental group : Patients intaking full-dose OAC + ASA 100mg od. Control group : Patients intaking full-dose OAC + Placebo of ASA 100mg od. Note: * For Apixaban: in case of \> 1 of the followings: \> 80 years old, weight \< 60kg, creatinine level \> 133μmol/l; Or a creatinine clearance between 30 and 50 ml/min (Cockroft Formula), the dose of Apixaban will be reduced to 2.5 mg bid. * For Rivaroxaban: in case of moderate creatinine clearance (Cockroft Formula) (between 30 and 50 ml/min) or severe renal insufficiency (between 15 and 29 ml/min) the dose of Rivaroxaban will be reduced to 15 mg od. * For Dabigatran: in case of moderate creatinine clearance (Cockroft Formula) (between 30 and 50 ml/min) with age between 75 and 80 years: the dose of Dabigatran will be 150 mg bid or 110 mg bid, according to the ischemic and hemorrhagic risk of the patient. In case of age \> 80 years and/or concomitant administration of Verapamil, the dose of Dabigatran will be reduced to 110 mg bid. * For VKA: target INR (International Normalised Ratio) between 2 and 3. The primary efficacy objective is to demonstrate, in high-risk stabilized patients after PCI requiring also anticoagulation for AF, the superiority of the dual therapy ASA 100mg od + full-dose of OAC for 24-48 months versus full-dose of OAC alone (+ placebo) on a composite endpoint associating: cardio-vascular (CV) mortality, myocardial infarction, stroke, coronary revascularization, systemic embolism, and acute limb ischemia. The primary safety objective is major bleeding (ISTH : International Society of Thrombosis and Haemostasis). The secondary efficacy objectives are evaluation of efficacy of dual therapy SA 100mg od + OAC full ose versus OAC alone (+placebo) for: * The composite of CV mortality, MI (Myocardial Infarction ), stroke * CV mortality * All cause death * Myocardial infarction (MI) * Stent thrombosis (definite or probable) * Stroke (ischemic, hemorrhagic, or stroke of uncertain cause, transient ischemic attack \[TIA\]) * Coronary revascularization * Systemic embolism * Acute limb ischemia Net clinical benefit: * All cause mortality * Major bleeding \[define according to the International Society of Thrombosis and Haemostasis (ISTH): an acute, linically overt bleeding accompanied by one or more of the following findings: 2g/dl decline in Hemoglobin level r = 2 red blood cell transfusions over a 24-hour period, leeding of a major organ (intracranial, intramedullary, intraocular, pericardial, interarticular, intramuscular and / or retro peritoneal) or fatal bleeding\] * Thrombotic cardiovascular events: * Myocardial infarction * Stent thrombosis * Stroke (ischemic, hemorrhagic, or stroke of uncertain cause, TIA) * Any coronary revascularization * Systemic embolism * Acute limb ischemia The secondary safety objectives are : * Major and clinically relevant non major bleeding (ISTH) * Major bleeding (TIMI : Thrombolysis In Myocardial Infarction) * Major bleeding (BARC ≥3 : Bleeding Academic Research Consortium) All the included patients will be randomized at visit 1 and followed every 6 months until death or the end of the study (i.e. achievement of 2-year follow-up of the last included patient, maximum of 48 month followup for the first included patient).The first patient may require up to 9 visits . 2000 patients are expected to be included. Inclusion period : 72 months. Duration of patient's participation: 24 to 48 months depending of time of inclusion. Total study duration: 48 months. All included patients will remain in the study until death or the end of the trial (i.e. achievement of 2-year follow-up of the last included patient).