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

NCT04217447 | Terminated Phase 3 DMC

• 1 other identifier: 29BRC19.0116
• Study Type: interventional
• Target: 874
• Locations: 1 country
• Sites: 51

Brief Summary

• 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.

Conditions

Coronary Artery Disease

Keywords

atrial fibrillation; oral anticoagulation; antithrombotic therapy

Outcome Measures

Primary Outcomes (2)

• Primary efficacy outcome : rate of composite of cardiovascular mortality and thrombotic cardiovascular events

  The primary efficacy outcome is the incidence of the adjudicated composite of (within 24-48 months): * CV mortality * Thrombotic cardiovascular events * Myocardial infarction * Stroke * Any coronary revascularization * Systemic embolism * Acute limb ischemia An Independent Clinical Events Committee (ICEC) will adjudicate all events (ischemic and bleeding events).

  within 24-48 months

• Primary safety outcome : rate of major bleeding

  The primary safety outcome is the occurrence of major bleeding according to the ISTH (International Society of Thrombosis and Haemostasis) definition

  within 24-48 months

Secondary Outcomes (2)

• Secondary efficacy outcomes : rate of composite of CV mortality, MI, stroke; CV mortality; all cause of death; thrombotic cardiovascular events.

  within 24-48 months

• Secondary safety outcomes : rate of major and clinically relevant non major bleeding

  within 24-48 months

Study Arms (2)

Experimental group

ACTIVE COMPARATOR

Patients intaking full-dose OAC + ASA 100mg od

Drug: OAC + Aspirin 100mg od

Control group

PLACEBO COMPARATOR

Patients intaking full-dose OAC + Placebo of ASA 100mg od

Drug: OAC + placebo of Aspirin 100mg od

Interventions

OAC + Aspirin 100mg od DRUG

Patients will receive full-dose of OAC + Aspirin 100mg od during 24 to 48 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)

Experimental group

OAC + placebo of Aspirin 100mg od DRUG

Patients will receive full-dose of OAC + placebo of Aspirin 100mg od during 24 to 48 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)

Control group

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients \>18 year-old
• All patients that need anticoagulation with direct oral anticoagulant (DOAC) or vitamin K antagonist (VKA) for AF (paroxysmal, persistent or permanent) or other indication and have a stabilized CAD (free from MI, or coronary revascularization in the past year) but remain at high residual risk of recurrent coronary and vascular events. The use of DOAC will be promoted as recommended by guidelines.
• High-risk of coronary and vascular event is defined as follow :
• History of PCI during an ACS involving placement of ≥1 stent(s) since \>6 months.
• History of PCI (\>6 months) outside the context of ACS but with high-risk features of ischemic event recurrences defined as: diabetes, or diffuse multivessel disease (defined by the involvement of the 3 coronary vessels), or chronic kidney disease (creatinine clearance \< 50ml/min), or prior stent thrombosis, or complex PCI (defined by: stenting of the last remaining patent coronary artery, left main, at least 3 stents implanted and/or 3 lesions treated, bifurcation with two stents, length of stent \>60mm and chronic total coronary occlusion) or the presence of peripheral artery disease (previous limb revascularization bypass or percutaneous angioplasty, previous limb or foot amputation for arterial vascular disease, history of intermittent claudication of peripheral artery stenosis (≥50%) ,previous carotid revascularization or carotid stenosis ≥50%).
• Women of childbearing potential with effective contraception defined as
• combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation :
• oral
• intravaginal
• transdermal
• progestogen-only hormonal contraception associated with inhibition of ovulation :
• oral
• injectable
• implantable
• intrauterine device (IUD)

You may not qualify if:

• Any coronary event within 6 months prior to randomization
• High risk of bleeding defined as recent (≤6 months) ISTH major bleeding event
• Constitutional or acquired haemorrhagic disease including gastrointestinal bleeding and thrombocytopenia
• Planned PCI within the next 6 months after randomization or subject requiring P2Y12 receptor antagonist therapy
• Stroke within 1 month or any history of hemorrhagic stroke
• Any contraindication to aspirin (ASA) or any of these excipients or other NSAIDs (hypersensitivity, allergy, active bleeding)
• Any contraindication to anticoagulant
• History (s) of asthma induced by the administration of salicylates or substances of close activity (especially NSAIDs)
• Evolutionary gastroduodenal ulcer
• Any other gastroduodenal history
• Severe renal insufficiency
• Severe hepatic insufficiency
• Severe, uncontrolled heart failure
• Lactose intolerance
• Pregnancy

Sponsors & Collaborators

• University Hospital, Brest: lead
• Bayer: collaborator

Study Sites (51)

CHRU d'Amiens

Amiens, France, 80054, France

Location

CHU d'Angers

Angers, France, 49933, France

Location

CH d'Annecy-Genevois

Annecy, France, 74370, France

Location

CH d'Antibes

Antibes, France, 06606, France

Location

CH d'Arras

Arras, France, 62000, France

Location

CH d'Avignon

Avignon, France, 84902, France

Location

CH de la Côte Basque - Bayonne

Bayonne, France, 64100, France

Location

Hôpital Haut Lévêque -CHU Bordeaux-Pessac

Bordeaux, France, 33604, France

Location

CHU de Brest

Brest, France, 29609, France

Location

Hôpital Louis Pradel - Bron

Bron, France, 69677, France

Location

Centre Hospitalier René Dubos - Cergy Pontoise

Cergy-Pontoise, France, 95301, France

Location

CH Chalon sur Saône

Chalon-sur-Saône, France, 71100, France

Location

CH Louis Pasteur - Chartres - Le Coudray

Chartres, France, 28630, France

Location

CHU de Clermont-Ferrand

Clermont-Ferrand, France, 63000, France

Location

CH Compiègne

Compiègne, France, 60200, France

Location

CH Sud Francilien Corbeil-Essonnes

Corbeil-Essonnes, France, 91106, France

Location

Hôpital Henri Mondor - Créteil

Créteil, France, 94000, France

Location

CHU de Dijon

Dijon, France, 21000, France

Location

GHM - Grenoble

Grenoble, France, 38028, France

Location

CHU de Grenoble

Grenoble, France, 38043, France

Location

Clinique St Clothilde -La Réunion

La Réunion, France, 97400, France

Location

CH de Lens

Lens, France, 62300, France

Location

CHRU de Lille

Lille, France, 59037, France

Location

CHU de Limoges

Limoges, France, 87042, France

Location

CH St Joseph-St Luc Lyon

Lyon, France, 69007, France

Location

Marseille-Hôpital Nord

Marseille, France, 13015, France

Location

Marseille- Hôpital La Timone

Marseille, France, 13385, France

Location

CH Martigues

Martigues, France, France

Location

CHU de Montpellier

Montpellier, France, 24298, France

Location

Clinique du Millénaire - Montpellier

Montpellier, France, 34000, France

Location

CHU de Nîmes

Nîmes, France, 30000, France

Location

CHR d'Orléans

Orléans, France, 45067, France

Location

Paris-Lariboisière

Paris, France, 75010, France

Location

Paris-Pitié-Salpêtrière

Paris, France, 75013, France

Location

Paris-HEGP Cardiologie

Paris, France, 75015, France

Location

Paris-HEGP Médecine vasculaire

Paris, France, 75015, France

Location

Paris-Bichat

Paris, France, 75877, France

Location

CH de Pau

Pau, France, 64000, France

Location

CH Périgueux

Périgueux, France, 24000, France

Location

CHU de Poitiers

Poitiers, France, 86021, France

Location

CHU de Rennes

Rennes, France, 35033, France

Location

Clinique St Hilaire - Rouen

Rouen, France, 76000, France

Location

CHU de Rouen

Rouen, France, 76031, France

Location

CH de Seclin

Seclin, France, 59113, France

Location

Clinique Rhena - Strasbourg

Strasbourg, France, 67000, France

Location

CHU de Strasbourg

Strasbourg, France, 67091, France

Location

CHU de Toulouse

Toulouse, France, 31059, France

Location

Clinique Pasteur-Toulouse

Toulouse, France, 31076, France

Location

CHRU de Tours

Tours, France, 37170, France

Location

Hôpital André Mignot - CH de Versailles

Versailles, France, 78153, France

Location

CHU de Nancy - Hôpitaux de Brabois

Vandœuvre-lès-Nancy, 54500, France

Location

Related Publications (1)

• Lemesle G, Didier R, Steg PG, Simon T, Montalescot G, Danchin N, Bauters C, Blanchard D, Bouleti C, Angoulvant D, Andrieu S, Vanzetto G, Kerneis M, Decalf V, Puymirat E, Mottier D, Diallo A, Vicaut E, Gilard M, Cayla G; AQUATIC Trial Investigators. Aspirin in Patients with Chronic Coronary Syndrome Receiving Oral Anticoagulation. N Engl J Med. 2025 Oct 23;393(16):1578-1588. doi: 10.1056/NEJMoa2507532. Epub 2025 Aug 31.

  PMID: 40888725 DERIVED

MeSH Terms

Conditions

Coronary Artery Disease; Atrial Fibrillation

Interventions

Aspirin

Condition Hierarchy (Ancestors)

Coronary Disease; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases; Arrhythmias, Cardiac; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Salicylates; Hydroxybenzoates; Phenols; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: It's a prospective, randomized, double-blind, placebo controlled, parallel-group, multi-center study.

Study Record Dates

• First Submitted: December 31, 2019
• First Posted: January 3, 2020
• Study Start: May 25, 2020
• Primary Completion: October 28, 2024
• Study Completion: October 28, 2024
• Last Updated: July 10, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will not share

Locations

FR (51)