Patients with atrial fibrillation undergoing percutaneous coronary intervention with stent implantation require treatment with different antithrombotic drugs. Oral anticoagulants are prescribed to reduce the risk of stroke associated with atrial fibrillation. Antiplatelet substances are prescribed after stent implantation to reduce the risk of adverse cardiac events such as myocardial infarction or stent thrombosis. Treatment with antithrombotic medications can cause bleeding complications, particularly when these substances are combined. The currently recommended standard strategy consists of treatment with 3 antithrombotic medications for at least 1 week up to one month, followed by treatment with two of these medications for up to 6-12 months after stent implantation. Thereafter, patients usually receive long-term treatment with only one drug, an anticoagulant. In the monotherapy group of this study, the investigators will investigate a strategy where only one antithrombotic drug will be used at a time. During the first month after stent implantation, the investigators will prescribe an antiplatelet medication, followed by an oral anticoagulant as monotherapy. This strategy might be associated with fewer bleeding complications, while protecting adequately against thrombotic events. In this study the investigators would like to investigate whether treatment with a single antithrombotic drug ("monotherapy strategy") is associated with benefits compared to the currently recommended combination therapy of antithrombotic medications ("standard-of-care strategy").
Background: The optimal antithrombotic treatment following percutaneous coronary intervention (PCI) in patients with atrial fibrillation (AF) requiring long-term oral anticoagulation remains a matter of debate. In particular, the appropriate intensity and duration of antithrombotic strategies to prevent ischemic events, while mitigating the risk of bleeding complications in this high bleeding risk population during the early peri-procedural period (within 30 days) and thereafter (from 30 days to 1 year) following drug-eluting stent implantation remains unclear. Aim: The investigators aim to assess the safety and efficacy of a P2Y12 inhibitor monotherapy regimen for 1 month followed by DOAC monotherapy long-term versus current standard of care consisting of triple antithrombotic therapy for up to one month (aspirin, P2Y12 inhibitor and DOAC) followed by dual antithrombotic therapy (P2Y12 inhibitor and DOAC) for 6 to 12 months and DOAC monotherapy thereafter, in AF patients undergoing PCI indicated for treatment with a DOAC after sirolimus-eluting Supraflex Cruz stent implantation and followed for a period of 12 months. Methodology: This investigator-initiated, multi-center, randomized, open-label, blinded evaluation, international clinical trial in 3010 AF patients with indication for long-term oral anticoagulation who have undergone successful PCI with Supraflex Cruz sirolimus-eluting biodegradable polymer cobalt chromium stent implantation. The study will be conducted at approximately 150 sites across Europe and Brazil. Patients will be randomized to the antithrombotic monotherapy (experimental antithrombotic strategy) or the standard of care strategy (control group) in a 1:1 ratio. Randomization is stratified by site, acute coronary syndrome (ACS) within the previous 6 months and CHA2DS2-VASc score ≥4. Patients randomized to the antithrombotic monotherapy treatment receive any of the commercially available oral P2Y12 inhibitors (clopidogrel, ticagrelor, prasugrel) and immediately discontinue aspirin and DOAC. After 1 month, the P2Y12 inhibitor will be stopped and treatment with a commercially available DOAC will be initiated for the duration of 11 months. Patients randomized to the standard of care strategy will initiate triple therapy for up to 1 month followed by dual anti-thrombotic therapy (consisting of P2Y12 inhibitor for a minimum of 6 and up to 12 months plus DOAC for at least 12 months). Potential significance: This is the first study investigation the impact of a short course of P2Y12 inhibitor monotherapy up to 1 month, while omitting clopidogrel non-responders, and temporarily omitting OAC, after stent implantation followed by OAC monotherapy in AF patients undergoing PCI. This sequential monotherapy treatment strategy has solid rational and carries potential to balance bleeding against cardiac and cerebral ischemic risks.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
3,010
The choice of P2Y12 inhibitor is left at investigator's discretion.
Aspirin is administered for up to 1 month after PCI at investigator's discretion
The choice of DOAC is left at investigator's discretion.
Hartcentrum Hasselt
Hasselt, Belgium
NOT_YET_RECRUITINGCHU Nîmes
Nîmes, France
NOT_YET_RECRUITINGUniversitätsklinikum Frankfurt/Main
Frankfurt am Main, Germany
NOT_YET_RECRUITINGKlinikum Friedrichshafen
Friedrichshafen, Germany
NOT_YET_RECRUITINGOspedale Ferrarotto
Catania, Catania CT, Italy
NOT_YET_RECRUITINGIRCCS Humanitas
Milan, Rozzano, Italy
NOT_YET_RECRUITINGUMC public
Amsterdam, Netherlands
NOT_YET_RECRUITINGUniwersytet Medyczny im. Karola Marcinkowskiego w Poznaniu
Poznan, Poland
NOT_YET_RECRUITINGHospital Universitario Marques de Valdecilla
Santander, Spain
NOT_YET_RECRUITINGCardiocentro Ticino Institute
Lugano, Canton Ticino, Switzerland
RECRUITING...and 5 more locations
The number of participants with a major adverse cardiac or cerebral events (MACCE), defined as the composite of death from any cause, myocardial infarction, stroke or non-central nervous system (non-CNS) systemic embolism
Time frame: 12 months
The number of participants with a major or clinically relevant non-major bleeding (MCB), defined according to the International Society of Thrombosis and Haemostasis (ISTH) criteria
Time frame: 12 months
The incidence of MACCE or MCB
MACCE, defined as the composite of death from any cause, myocardial infarction, stroke or non-CNS systemic embolism and MCB, defined according to the ISTH criteria
Time frame: 12 months
The incidence of MACCE or MCB
MACCE, defined as the composite of death from any cause, myocardial infarction, stroke or non-CNS systemic embolism and MCB, defined according to the ISTH criteria
Time frame: 15 months
The number of participants with a composite of death from cardiovascular causes, myocardial infarction or stroke
Time frame: 12 months
The number of participants with a composite of death from cardiovascular causes, myocardial infarction or stroke
Time frame: 15 months
The number of participants with a composite of death from cardiovascular causes, myocardial infarction, stroke or non-CNS systemic embolism
Time frame: 12 months
The number of participants with a composite of death from cardiovascular causes, myocardial infarction, stroke or non-CNS systemic embolism
Time frame: 15 months
The number of participants died from cardiovascular or non-cardiovascular causes
Time frame: 12 months
The number of participants died from cardiovascular or non-cardiovascular causes
Time frame: 15 months
The number of participants with a composite of stroke and non-CNS systemic embolism
Time frame: 12 months
The number of participants with a composite of stroke and non-CNS systemic embolism
Time frame: 15 months
The number of participants with any stroke (including ischemic, hemorrhagic and unknown types)
Time frame: 12 months
The number of participants with any stroke (including ischemic, hemorrhagic and unknown types)
Time frame: 15 months
The number of participants with an ischaemic stroke
Time frame: 12 months
The number of participants with an ischaemic stroke
Time frame: 15 months
The number of participants with a hemorrhagic stroke
Time frame: 12 months
The number of participants with a hemorrhagic stroke
Time frame: 15 months
The number of participants with a transient ischemic attack
Time frame: 12 months
The number of participants with a transient ischemic attack
Time frame: 15 months
The number of participants with a composite of definite or probable stent thrombosis
Time frame: 12 months
The number of participants with a composite of definite or probable stent thrombosis
Time frame: 15 months
The number of participants with a definite stent thrombosis
Time frame: 12 months
The number of participants with a definite stent thrombosis
Time frame: 15 months
The number of participants with a hospitalization
Time frame: 12 months
The number of participants with a hospitalization
Time frame: 15 months
The number of participants with a composite of death or hospitalization
Time frame: 12 months
The number of participants with a composite of death or hospitalization
Time frame: 15 months
The number of participants with any target lesion revascularization
Time frame: 12 months
The number of participants with any target lesion revascularization
Time frame: 15 months
The number of participants with any target vessel revascularization
Time frame: 12 months
The number of participants with any target vessel revascularization
Time frame: 15 months
The number of participants with any revascularization
Time frame: 12 months
The number of participants with any revascularization
Time frame: 15 months
The number of all bleeding events, also adjudicated according to Bleeding Academic Research Consortium, Thrombolysis in Myocardial Infarction or Global Use of Strategies to Open Occluded Coronary Arteries scales
The BARC is scaled from 0 to 5, with higher scores indicating worse outcomes, the TIMI from minor to major to fatal bleeding, and the GUSTO from mild to moderate to severe or life-threatening.
Time frame: 12 months
The number of all bleeding events, also adjudicated according to Bleeding Academic Research Consortium, Thrombolysis in Myocardial Infarction or Global Use of Strategies to Open Occluded Coronary Arteries scales
The BARC is scaled from 0 to 5, with higher scores indicating worse outcomes, the TIMI from minor to major to fatal bleeding, and the GUSTO from mild to moderate to severe or life-threatening.
Time frame: 15 months
Transfusion rates both in patients with and/or without clinically detected overt bleeding
Time frame: 12 months
Transfusion rates both in patients with and/or without clinically detected overt bleeding
Time frame: 15 months
The number of participants with a major adverse cardiac or cerebral events (MACCE), defined as the composite of death from any cause, myocardial infarction, stroke or non-central nervous system (non-CNS) systemic embolism
Time frame: 15 months
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