Edoxaban Treatment Versus Vitamin K Antagonist in Patients With Atrial Fibrillation Undergoing Percutaneous Coronary Intervention
- Conditions
- Atrial Fibrillation
- Interventions
- Registration Number
- NCT02866175
- Lead Sponsor
- Daiichi Sankyo Europe, GmbH, a Daiichi Sankyo Company
- Brief Summary
There are insufficient data on the safety and efficacy of edoxaban plus antiplatelet therapy in subjects with atrial fibrillation (AF) following percutaneous intervention (PCI) with stenting. This study is designed to evaluate the safety and to explore the efficacy of an edoxaban-based antithrombotic regimen versus a vitamin K antagonist (VKA)-based antithrombotic regimen in subjects with AF following PCI with stent placement. Bleeding is a central safety outcome in cardiovascular clinical trials, especially for antithrombotic strategies and invasive procedures.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 1506
- Oral anticoagulant (OAC) indication for atrial fibrillation for a period of at least 12 months following successful PCI with stenting.
Eligibility is assessed 4 hours after sheath removal and within 5 days after successful PCI with stent placement. If a staged PCI is planned, eligibility is assessed after completion of the last stage.
Successful PCI definition:
The success of a PCI procedure is defined by 2 interrelated components: angiographic findings, procedural / clinical outcomes as detailed below:
Angiographic Success A minimum stenosis diameter of < 20% (as visually assessed by angiography - residual blockage or stenosis reduced to less than 20% of the artery's diameter).
Sufficient enlargement of the lumen at the target site to improve coronary artery blood flow with final thrombolysis in myocardial infarction (TIMI) flow grade 3 (visually assessed by angiography), without occlusion of a significant side branch, flow-limiting dissection, distal embolization, or angiographic thrombus.
Procedural Success No major in-hospital clinical complications(e.g. ongoing International Society on Thrombosis and Haemostasis [ISTH] major or clinical relevant non-major procedural bleeding at the time of randomization, stroke, emergency coronary artery bypass graft [CABG]).
In summary, a clinically successful PCI requires both anatomic and procedural success along with relief of signs and/or symptoms of myocardial ischemia at the time of randomization.
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Bleeding risks or systemic conditions
-
Known bleeding diathesis, including but not limited to,
-
Uncontrolled active bleeding, encompassing both ISTH major and clinically relevant non-major bleeding, preceding randomization.
Lesion or condition, if considered to be a significant risk for major bleeding. This may include but is not limited to: unresolved gastrointestinal ulceration, presence of malignant neoplasms at high risk of bleeding (e.g. malignancies with metastasis), recent unresolved brain or spinal injury, recent brain, spinal or ophthalmic surgery, any intracranial hemorrhage, known or suspected esophageal varices, arteriovenous malformations, vascular aneurysms (of more than 3.5 cm) or major intraspinal or intracerebral vascular abnormalities.
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Medication-related
-
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International normalized ratio (INR) > 2.5 (the participant can be reconsidered at a later time, but within 5 days of sheath removal).
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Contraindication to edoxaban, VKA, acetylsalicylic acid (ASA) and/or P2Y12 antagonists;
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Concomitant treatment with other antithrombotic agents, fibrinolytic therapy and chronic nonsteroidal anti-inflammatory drugs (NSAIDs).
Concomitant conditions and therapies
-
Critically ill or hemodynamically unstable subjects (at the time of randomization) including:
- cardiogenic shock or acute decompensated heart failure, with the requirement for vasopressor agents or inotropic support or mechanical support to support circulation
- respiratory failure requiring endotracheal intubation and mechanical ventilation.
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Any prior mechanical valvular prosthesis;
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Planned coronary or vascular intervention or major surgery within 12 months; Randomization must be deferred to the last stage in a multistep, multivessel PCI procedure;
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Moderate or severe mitral stenosis;
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Ischemic stroke within 2 weeks prior to randomization;
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Uncontrolled severe hypertension with a systolic blood pressure (BP) ≥180 mmHg and/or diastolic BP ≥ 120 mmHg;
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End stage renal disease (ESRD) (CrCL < 15 mL/min or on dialysis);
-
Known abnormal liver function prior to randomization (including hepatic disease or biochemical evidence of significant liver derangement known prior to randomization).
Other exclusion criteria
-
Any of the following abnormal local laboratory results prior to randomization:
- Platelet count < 50 x10^9/L
- Hemoglobin < 8 mg/dL
-
Unable to provide written Informed Consent;
-
Female participants of childbearing potential without using highly effective contraception (female of childbearing potential is defined as one who has not been postmenopausal for at least one year, or has not been surgically sterilised, or has not had a hysterectomy at least three months prior to the start of this study). Females taking oral contraceptives should have been on therapy for at least three months. Adequate contraceptives include: Combined (estrogen and progestogen containing) oral, intravaginal, transdermal, hormonal contraception associated with inhibition of ovulation; intrauterine device (IUD); intrauterine hormone-releasing system (IUS); bilateral tubal occlusion; vasectomized partner; sexual abstinence;
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Pregnant or breast-feeding participants;
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Assessment that the participant is not likely to comply with the study procedures or have complete follow-up;
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Participating in another clinical trial that potentially interferes with the current study;
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Previous randomization in this study;
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Active on prescription drug abuse and addiction; abuse of illicit substances (i.e. marijuana, cocaine, methamphetamine, heroin) and alcohol abuses during the last 12 months according to the judgement of the investigator;
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Life expectancy < 12 months.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Edoxaban Regimen Edoxaban Participants will be randomized to receive edoxaban 60 mg once-daily or 30 mg once-daily and clopidogrel 75 mg once-daily (or in the presence of a documented clinical need prasugrel \[5 mg or 10 mg once-daily\] or ticagrelor \[90 mg twice-daily\] may be used) used. Vitamin K Antagonist Regimen Vitamin K antagonist Participants will be randomized to receive VKA in combination with clopidogrel 75 mg once-daily (or in the presence of a documented clinical need prasugrel \[5mg or 10 mg once-daily\] or ticagrelor \[90 mg twice-daily\] may be used) and aspirin (100 mg once-daily, for a minimum of 1 month and up to 12 months duration. Edoxaban Regimen Clopidogrel Participants will be randomized to receive edoxaban 60 mg once-daily or 30 mg once-daily and clopidogrel 75 mg once-daily (or in the presence of a documented clinical need prasugrel \[5 mg or 10 mg once-daily\] or ticagrelor \[90 mg twice-daily\] may be used) used. Edoxaban Regimen Prasugrel Participants will be randomized to receive edoxaban 60 mg once-daily or 30 mg once-daily and clopidogrel 75 mg once-daily (or in the presence of a documented clinical need prasugrel \[5 mg or 10 mg once-daily\] or ticagrelor \[90 mg twice-daily\] may be used) used. Edoxaban Regimen Ticagrelor Participants will be randomized to receive edoxaban 60 mg once-daily or 30 mg once-daily and clopidogrel 75 mg once-daily (or in the presence of a documented clinical need prasugrel \[5 mg or 10 mg once-daily\] or ticagrelor \[90 mg twice-daily\] may be used) used. Vitamin K Antagonist Regimen Clopidogrel Participants will be randomized to receive VKA in combination with clopidogrel 75 mg once-daily (or in the presence of a documented clinical need prasugrel \[5mg or 10 mg once-daily\] or ticagrelor \[90 mg twice-daily\] may be used) and aspirin (100 mg once-daily, for a minimum of 1 month and up to 12 months duration. Vitamin K Antagonist Regimen Prasugrel Participants will be randomized to receive VKA in combination with clopidogrel 75 mg once-daily (or in the presence of a documented clinical need prasugrel \[5mg or 10 mg once-daily\] or ticagrelor \[90 mg twice-daily\] may be used) and aspirin (100 mg once-daily, for a minimum of 1 month and up to 12 months duration. Vitamin K Antagonist Regimen Ticagrelor Participants will be randomized to receive VKA in combination with clopidogrel 75 mg once-daily (or in the presence of a documented clinical need prasugrel \[5mg or 10 mg once-daily\] or ticagrelor \[90 mg twice-daily\] may be used) and aspirin (100 mg once-daily, for a minimum of 1 month and up to 12 months duration.
- Primary Outcome Measures
Name Time Method Number of Participants With Adjudicated Major or Clinically Relevant Non-major Bleeding As First Event Defined by International Society on Thrombosis and Haemostasis Following Edoxaban-based Regimen Compared With Vitamin K Antagonist (VKA)-Based Regimen Day 1 to 12 months postdose Participants' first major or clinically relevant non-major bleeding (MCRB) events were reported. International Society on Thrombosis and Hemostasis (ISTH) defined bleeding events included: MCRB, major bleeding, including fatal bleeding (intracranial and non-intracranial), symptomatic intracranial hemorrhage, symptomatic bleeding in a critical area or organ, and clinically overt and causing ≥2.0 g/dL adjusted hemoglobin loss, clinically relevant non-major (CRNM) bleeding, minor bleedings, any bleeding (defined as the composite of major, CRNM, and minor bleeding), life-threatening bleeding, provoked (spontaneous, instrumental/traumatic, unknown) bleeding, and spontaneous bleeding.
- Secondary Outcome Measures
Name Time Method Number of Participants With Bleeding Academic Research Consortium (BARC) Type 1, 2, 3, and 5 Bleeding According to the BARC Definitions Following Edoxaban-based Regimen Compared With Vitamin K Antagonist (VKA)-Based Regimen Day 1 to 12 months postdose Bleeding Academic Research Consortium (BARC) bleeding events included: Bleeding (defined by BARC type 3 or 5), bleeding (defined by BARC type 2, 3, or 5), and any bleeding (defined as the composite of BARC type 1, 2, 3, or 5), where increases in BARC type indicate worse outcome.
Type 1: bleeding that is not actionable and does not cause the patient to seek unscheduled performance of studies, hospitalization, or treatment by a healthcare professional; may include episodes leading to self-discontinuation of medical therapy by the patient without consultation; Type 2: any overt, actionable sign of hemorrhage that does not fit the criteria for type 3, 4, or 5 but does meet at least one of the following criteria: (1) requiring nonsurgical, medical intervention, (2) leading to hospitalization or increased level of care, or (3) prompting evaluation; Type 3: Overt bleeding plus hemoglobin drop of 3 to ≤5 g/dL (3a), ≥5 g/dl (3b), and intracranial hemorrhage (3c) Type 5: Fatal bleedingNumber of Participants With Adjudicated Major, Minor, and Minimal Bleeding by Thrombolysis in Myocardial Infarction (TIMI) Definition Following Edoxaban-based Regimen Compared With Vitamin K Antagonist (VKA)-Based Regimen Day 1 to 12 months postdose Thrombolysis in Myocardial Infarction (TIMI) defined bleeding events included: Major bleeding (including fatal bleeding and non-fatal bleeding \[fulfilling the TIMI major bleeding definition\], major or minor bleeding, minor bleeding, minimal bleeding, and any bleeding (defined as composite of major, minor, and minimal bleeding)
Number of Participants With Adjudicated Major, Clinically Relevant Non-major and Minor Bleeding (All Events) Defined by International Society on Thrombosis and Haemostasis Following Edoxaban-based Regimen Compared With Vitamin K Antagonist-Based Regimen Day 1 to 12 months postdose All major, clinically relevant non-major and minor bleeding are reported for the secondary outcome. Participants may have experiences more than 1 bleeding event, all occurrences are reported. Participants with International Society on Thrombosis and Hemostasis (ISTH) defined bleeding events included: major or clinically relevant non-major bleeding (MCRB), major bleeding, including fatal bleeding (intracranial and non-intracranial), symptomatic intracranial hemorrhage, symptomatic bleeding in a critical area or organ, and clinically overt and causing ≥2.0 g/dL adjusted hemoglobin loss, clinically relevant non-major (CRNM) bleeding, minor bleedings, any bleeding (defined as the composite of major, CRNM, and minor bleeding), life-threatening bleeding, provoked (spontaneous, instrumental/traumatic, unknown) bleeding, and spontaneous bleeding.
Number of Participants With Main Efficacy Endpoints For the Overall Study Period Following Edoxaban-based Regimen Compared With Vitamin K Antagonist (VKA)-Based Regimen Day 1 to 12 months postdose The main efficacy endpoints were defined as the composite of cardiovascular death (ARC), stroke (protocol defined), systemic embolic event (SEE), myocardial infarction (MI), or definite stent thrombosis.
Number of Participants With Treatment-emergent Adverse Events (TEAEs) Following Edoxaban-based Regimen Compared With Vitamin K Antagonist (VKA)-Based Regimen Day 1 to 30 days after the last dose Treatment-emergent adverse events (TEAEs) in \>1.0% of participants were defined as events which started on or after first dose of the assigned study drug (edoxaban and VKA) or started prior to but then worsened after the first dose of the assigned study drug.
Number of Participants With Study Drug-related Treatment-emergent Adverse Events (TEAEs) Experienced by 2 or More Participants Following Edoxaban-based Regimen Compared With Vitamin K Antagonist (VKA)-Based Regimen Day 1 to 30 days after the last dose Study drug-related treatment-emergent adverse events (TEAEs) (experienced by 2 or more participants) were defined as events which started on or after first dose of the assigned study drug (edoxaban and VKA) or started prior to but then worsened after the first dose of the assigned study drug and were found to be related to treatment by the Investigator.
Trial Locations
- Locations (200)
Kharkiv City Clinical Hospital #8
🇺🇦Kharkiv, Ukraine
Altnagelvin Area Hospital
🇬🇧Londonderry, United Kingdom
Golden Jubilee Hospital
🇬🇧Clydebank, United Kingdom
Daegu Catholic University Hospital
🇰🇷Daegu, Korea, Republic of
Chonnam National University Hospital
🇰🇷Gwangju, Korea, Republic of
The Catholic University of Korea St.Vincent's Hospital
🇰🇷Gyeonggi-do, Korea, Republic of
Hallym University Sacred Heart Hospital
🇰🇷Gyeonggi-do, Korea, Republic of
Inha University Hospital
🇰🇷Incheon, Korea, Republic of
Seoul National University Hospital
🇰🇷Seoul, Korea, Republic of
Chonbuk National University Hospital
🇰🇷Jeonju, Korea, Republic of
Universitätsklinikum des Saarlandes Innere Medizin III - Kardiologie, Angiologie und internistische Intensivmedizin
🇩🇪Homburg, Germany
Herzzentrum Leipzig - Universitätsklinik Klinik für Innere Medizin/Kardiologie
🇩🇪Leipzig, Germany
Hospital La Paz, Madrid
🇪🇸Madrid, Spain
Hospital Ramon y Cajal
🇪🇸Madrid, Spain
Ospedale degli Infermi di Rivoli
🇮🇹Rivoli, Italy
Imelda Ziekenhuis
🇧🇪Bonheiden, Belgium
Hopital Cote Basque
🇫🇷Bayonne, France
University Hospital Antwerp
🇧🇪Edegem, Belgium
Chru Jean Minjoz
🇫🇷Besancon, France
Hôpital Rangueil, Service Cancérologie
🇫🇷Toulouse, France
University Hospital Innsbruck
🇦🇹Innsbruck, Austria
Wilhelminenspital
🇦🇹Wien, Austria
ASZ Aalst
🇧🇪Aalst, Belgium
University Hospital of Angers
🇫🇷Angers, France
CHU de Nice
🇫🇷Nice, France
Hospital Henri Mondor
🇫🇷Creteil, France
Clinique Vauban
🇫🇷Valenciennes, France
AZ St Jan
🇧🇪Brugge, Belgium
AZ Delta
🇧🇪Roeselare, Belgium
Metropole Savoie Hospital
🇫🇷Chambery, France
Hôpital Bichat - Claude Bernard
🇫🇷Paris cedex 8, France
Universitäts-Herzzentrum Freiburg • Bad Krozingen
🇩🇪Bad Krozingen, Germany
Städtisches Klinikum Lüneburg
🇩🇪Lüneburg, Germany
Charité, Campus Virchow-Klinikum - Medizinische Klinik mit Schwerpunkt Kardiologie
🇩🇪Berlin, Germany
Universitätsklinikum Jena Klinik für Innere Medizin I, Kardiologie, Angiologie, Pneumologie, Internistische Intensivmedizin
🇩🇪Jena, Germany
Klinikum Coburg Med. Klinik Kardiologie, Angiologie, Pneumologie
🇩🇪Coburg, Germany
University Hospital Aachen
🇩🇪Aachen, Germany
Kerckhoff Klinik
🇩🇪Bad Nauheim, Germany
GFO Kliniken Bonn - St.-Marien-Hospital
🇩🇪Bonn, Germany
Universitätsklinikum Bonn - Medizinische Klinik II - Innere Medizin (Kardiologie, Angiologie und Pneumologie)
🇩🇪Bonn, Germany
Vivantes Klinikum im Friedrichshaim
🇩🇪Berlin, Germany
Charité Benjamin Franklin
🇩🇪Berlin, Germany
Ospedale San Donato- ASL 8 Arezzo
🇮🇹Arezzo, Italy
Policlinico di Bari
🇮🇹Bari, Italy
Ospedale Maggiore C.A. Pizzardi -OR - Laboratorio di Cardiologia Interventistica
🇮🇹Bologna, Italy
AOU Materdomini, Magna Graecia University
🇮🇹Catanzaro, Italy
Békés Megyei Központi Kórház
🇭🇺Gyula, Hungary
Heinrich-Heine-Universität Düsseldorf - Universitätsklinikum Düsseldorf (UKD) Klinik für Kardiologie, Pneumologie und Angiologie
🇩🇪Düsseldorf, Germany
Szabolcs-Szatmár-Bereg Megyei Kórházak és Egyetemi Oktatókórház, Jósa András Oktatókórház
🇭🇺Nyíregyháza, Hungary
Budai Irgalmasrendi Kht.
🇭🇺Budapest, Hungary
Gottsegen György Országos Kardiológiai Intézet
🇭🇺Budapest, Hungary
ASL2 Chieti - SS Maria Annunziata
🇮🇹Chieti, Italy
A.S.O.S. Croce e Carle Cuneo
🇮🇹Cuneo, Italy
Ospedale Careggi
🇮🇹Firenze, Italy
Asst Fatebenefratelli-Sacco
🇮🇹Milano, Italy
AOU Policlinico di Modena
🇮🇹Modena, Italy
Klinikum Ludwigshafen
🇩🇪Ludwigshafen, Germany
St. Johannes- Hospital
🇩🇪Dortmund, Germany
Universitaetsklinikum Freiburg Klinik für Kardiologie und Angiologie I
🇩🇪Freiburg, Germany
Klinik Dr. Müller GmbH & Co. KG, Peter Osypka Herzzentrum
🇩🇪München, Germany
Universitäts Klinikum Tübingen
🇩🇪Tübingen, Germany
Herzklinik Ulm
🇩🇪Ulm, Germany
Állami Szívkórház
🇭🇺Balatonfüred, Hungary
Universitätsklinikum Münster - Department für Kardiologie und Angiologie
🇩🇪Münster, Germany
Universitätsmedizin Rostock
🇩🇪Rostock, Germany
HELIOS Klinikum Wuppertal - Herzzentrum
🇩🇪Wuppertal, Germany
AOU Sant'Anna
🇮🇹Ferrara, Italy
Ospedali Riuniti di Foggia
🇮🇹Foggia, Italy
Ospedale Alessandro Manzoni-Azienda Ospedaliera di Lecco
🇮🇹Lecco, Italy
University Hospital Federico II
🇮🇹Napoli, Italy
Azienda Ospedaliero-Universitaria di Parma
🇮🇹Parma, Italy
Ospedale degli Infermi
🇮🇹Rimini, Italy
S.Camillo Forlanini - Ospedale S.Camillo Reparto di Emodinamica
🇮🇹Rome, Italy
Bolognini Hospital Seriate
🇮🇹Seriate, Italy
Padova University Hospital
🇮🇹Padova, Italy
"Santa Maria" University Hospital - Azienda Ospedaliera Santa Maria Di Terni
🇮🇹Terni, Italy
Policlinico Agostino Gemelli
🇮🇹Roma, Italy
U.O. Cardiologia Ospedale Borgo Trento
🇮🇹Verona, Italy
Inje Univ. Ilsan Paik Hospital
🇰🇷Gyeonggi-do, Korea, Republic of
Republican Siauliai Hospital
🇱🇹Šiauliai, Lithuania
Seoul National University Bundang Hospital
🇰🇷Seongnam, Korea, Republic of
Centro Hospitalar e Universitário de Coimbra, EPE - Hospital dos Covões
🇵🇹Coimbra, Portugal
Lithuanian University of Health Sciences hospital
🇱🇹Kaunas, Lithuania
Severance Hospital
🇰🇷Seoul, Korea, Republic of
University Hospital of Bucharest
🇷🇴Bucharest, Romania
Oradea Emergency County Clinical Hospital
🇷🇴Oradea, Romania
Klaipeda Seamen's Hospital
🇱🇹Klaipėda, Lithuania
Clinical Center of Serbia
🇷🇸Belgrade, Serbia
St Antonius Hospital
🇳🇱Nieuwegein, Netherlands
Maasstad Hospital
🇳🇱Rotterdam, Netherlands
Korea University Guro Hospital
🇰🇷Seoul, Korea, Republic of
Vilnius University Hospital "Santariskiu Clinic"
🇱🇹Vilnius, Lithuania
II Oddział Kardiologiczny, Polsko-Amerykanskie Kliniki Serca
🇵🇱Bielsko-Biala, Poland
MCSN AHoP
🇵🇱Chrzanów, Poland
Krakowski Szpital Specjalistyczny im. Jana Pawła II, Oddział Kliniczny Kardiologii Interwencyjnej z Pododdziałem Intenyswengo Nadzoru Kardiologicznego
🇵🇱Kraków, Poland
Korea University Anam Hospital
🇰🇷Seoul, Korea, Republic of
AHP IV DEP K-Kozle
🇵🇱Kędzierzyn-Koźle, Poland
Nyskie Centrum Sercowo-Naczyniowe, Polsko-Amerykanskie Kliniki Serca
🇵🇱Nysa, Poland
Clin-Medica OMC sp. z o.o. s.k.
🇵🇱Skierniewice, Poland
Hospital Universitario 12 de Octubre
🇪🇸Madrid, Spain
Bellvitge University Hospital
🇪🇸L'Hospitalet de Llobregat, Spain
Emergency Institute of Cardiovascular Diseases and Transplantation
🇷🇴Târgu-Mureş, Romania
Complejo Asistencial Universitario de León
🇪🇸León, Spain
Centro Hospitalar de Lisboa Central, EPE - Hospital Santa Marta
🇵🇹Lisboa, Portugal
Saint John Emergency Hospital
🇷🇴Bucharest, Romania
Clinical Center Kragujevac
🇷🇸Kragujevac, Serbia
HFR Freiburg - Kantonsspital Kardiologie
🇨🇭Fribourg, Switzerland
"Prof. C.C. Iliescu" Emergency Institute for Cardiovascular Diseases
🇷🇴Bucharest, Romania
Far Eastern Memorial Hospital (FEMH)
🇨🇳New Taipei City, Taiwan
Hospital Universitari Germans Trias i Pujol
🇪🇸Badalona, Spain
X Oddział Kardiologii Inwazyjnej, Elektrofizjologii i Elektrostymulacji Polsko-Amerykanskie Kliniki Serca
🇵🇱Tychy, Poland
Hospital Garcia de Orta, EPE
🇵🇹Almada, Portugal
Centro Hospitalar de Lisboa Ocidental, EPE - Hospital de Santa Cruz
🇵🇹Carnaxide, Portugal
Hospital Universitario Virgen de la Arrixaca
🇪🇸Murcia, Spain
Cardiocentro Ticino
🇨🇭Lugano, Switzerland
Kaohsiung medical University Chung-Ho Memorial Hospital (KMUH)
🇨🇳Kaohsiung, Taiwan
Instytut Kardiologii im. Prymasa Tysiąclecia Stefana Kardynała Wyszyńskiego; Klinika Kardiologii i Angiologii Interwencyjnej
🇵🇱Warsaw, Poland
Emergency County Hospital Baia Mare
🇷🇴Baia Mare, Romania
Institutul de Boli Cardiovasculare Timisoara
🇷🇴Timişoara, Romania
Nzoz Salus
🇵🇱Łódź, Poland
Clinical Hospital Center -Zvezdara
🇷🇸Belgrade, Serbia
Institute of CV Diseases Clinical Center of Serbia
🇷🇸Belgrade, Serbia
General University Hospital of Alicante
🇪🇸Alicante, Spain
Clinica Universitaria San Carlos
🇪🇸Madrid, Spain
Complejo Hospitalario Universitario de Granada
🇪🇸Granada, Spain
Centro Hospitalar e Universitário de Coimbra, EPE
🇵🇹Coimbra, Portugal
Institute of Cardiovascular Diseases of Vojvodina
🇷🇸Sremska Kamenica, Serbia
Hospital Universitario de Salamanca
🇪🇸Salamanca, Spain
Hospital Clínico Universitario de Valladolid
🇪🇸Valladolid, Spain
Hospital Álvaro Cunqueiro
🇪🇸Vigo, Spain
Chi-Mei Medical Center (CMMC)
🇨🇳Tainan, Taiwan
Cherkasy regional cardiological center
🇺🇦Cherkasy, Ukraine
Chernihiv City Hospital #2
🇺🇦Chernihiv, Ukraine
Nikolaev Regional Clinical Hospital
🇺🇦Nikolayev, Ukraine
Odessa Regional Hospital, Cardiosurgery Center
🇺🇦Odessa, Ukraine
Communal Institution Rivne Regional Clinical Hospital
🇺🇦Rivne, Ukraine
Southern Health and Social Care Trust
🇬🇧Portadown, United Kingdom
Magyar Honvédség Egészségügyi Központ
🇭🇺Budapest, Hungary
Pécsi Tudományegyetem
🇭🇺Pécs, Hungary
Bajcsy-Zsilinszky Kórház és Rendelőintézet
🇭🇺Budapest, Hungary
Debreceni Egyetem Klinikai Központ
🇭🇺Debrecen, Hungary
Petz Aladar Megyei Oktato Korhaz
🇭🇺Győr, Hungary
Szegedi Tudományegyetem
🇭🇺Szeged, Hungary
Universitäres Herzzentrum Hamburg GmbH (UHZ)
🇩🇪Hamburg, Germany
Medizinische Universitaetsklinik Graz
🇦🇹Graz, Austria
Krankenhaus Hietzing
🇦🇹Wien, Austria
Hopital Erasme
🇧🇪Brussel, Belgium
Virga Jesse Jessa hospital
🇧🇪Hasselt, Belgium
Centre Hospitalier Sud Francilien
🇫🇷Corbeil Essonnes Cedex, France
Kliniken Maria Hilf GmbH
🇩🇪Mönchengladbach, Germany
Schwarzwald-Baar Klinikum - Kliniken Villingen-Schwenningen - Innere Medizin III: Kardiologie und Intensivmedizin
🇩🇪Villingen-Schwenningen, Germany
Universitätsklinik Ulm - Zentrum für Innere Medizin - Klinik für Innere Medizin II
🇩🇪Ulm, Germany
St. Josefs-Hospital - Medizinische Klinik I, Kardiologie
🇩🇪Wiesbaden, Germany
MC Haaglanden
🇳🇱The Hague, Netherlands
Pusan National University Hospital
🇰🇷Busan, Korea, Republic of
Boramae Medical Center
🇰🇷Seoul, Korea, Republic of
SEOUL St.Maria
🇰🇷Seoul, Korea, Republic of
Radboud university medical center
🇳🇱Nijmegen, Netherlands
III Oddział Kardiologii Inwazyjnej, Angiologii i Elektrokardiologii Polsko-Amerykanskie Kliniki Serca
🇵🇱Dąbrowa Górnicza, Poland
Chang-Gung Memorial Hospital
🇨🇳Taoyuan, Taiwan
Instytut Kardiologii im. Prymasa Tysiaclecia Kardynala Stefana Wyszynskiego, Klinika Choroby Wieńcowej i Strukturalnych Chorób Serca
🇵🇱Warszawa, Poland
Centro Hospitalar de Lisboa Norte, EPE - Hospital de Santa Maria
🇵🇹Lisboa, Portugal
Hospital Universitario Puerta de Hierro
🇪🇸Madrid, Spain
Hospital Universitario Virgen de La Victoria
🇪🇸Málaga, Spain
Hospital Universitari i Politècnic La Fe
🇪🇸Valencia, Spain
Hsinchu Mackay Memorial Hospital (HMMH)
🇨🇳Hsinchu, Taiwan
E-DA Hospital
🇨🇳Kaohsiung, Taiwan
National Cheng Kung University Hospital
🇨🇳Tainan, Taiwan
China Medical University Hospital (CMUH)
🇨🇳Taichung, Taiwan
Cheng Hsin General Hospital
🇨🇳Taipei, Taiwan
Chernivtsi Regional Clinical Cardiology Dispensary
🇺🇦Chernivtsi, Ukraine
Communal Institution Dnepropetrovsk Regional Diagnostic Center
🇺🇦Dnipro, Ukraine
CI "Dnipropetrovsk Joint Emergency Hospital"
🇺🇦Dnipropetrovsk, Ukraine
Ivano-Frankivsk Central City Clinical Hospital
🇺🇦Ivano-Frankivs'k, Ukraine
Kharkiv Railway Clinical Hospital N1 of Brance "Health Center" of the Public joint stock company "Ukrainian Railway"
🇺🇦Kharkov, Ukraine
Khmelnytskyy regional hospital
🇺🇦Khmel'nyts'kyy, Ukraine
Communal Health Care Institution "Regional Clinical Hospital - Center of Emergency Medical Care and Disaster Medicine"
🇺🇦Kharkiv, Ukraine
Kyiv City Clinical Hospital#5
🇺🇦Kyiv, Ukraine
State Institution 'National Scientific Central Institute of Cardiology named after MD Strazhesko'
🇺🇦Kyiv, Ukraine
Insititute of Heart of MoH Ukraine
🇺🇦Kyiv, Ukraine
Oleksandrivska Kiyv City Clinical Hospital
🇺🇦Kyiv, Ukraine
Communal Institution of Kyiv Regional Rada
🇺🇦Kyiv, Ukraine
Lviv Regional State Clinical Treatment and Diagnostic Cardiology Center
🇺🇦L'viv, Ukraine
Communal Institution of Sumy Regional Rada
🇺🇦Sumy, Ukraine
Communal Institution "Vinnytsia Regional Diagnostic Center of cardiovascular disease"
🇺🇦Vinnytsya, Ukraine
Vinnytsya Regional Clinical Hospital n.a. Pyrogov
🇺🇦Vinnytsya, Ukraine
University Hospital of Wales
🇬🇧Cardiff, United Kingdom
Blackpool Victoria Hospital
🇬🇧Blackpool, Lancashire, United Kingdom
Zaporizhzhia Regional cardiology dispensary
🇺🇦Zaporizhzhia, Ukraine
Universitätsklinikum Heidelberg Klinik für Kardiologie, Angiologie und Pneumologie (Innere Medizin III)
🇩🇪Heidelberg, Germany
Fejér Megyei Szent György Egyetemi Oktató Kórház
🇭🇺Székesfehérvár, Hungary
Staedtische Kliniken Bielefeld
🇩🇪Bielefeld, Germany
Samsung Medical Centre
🇰🇷Seoul, Korea, Republic of
St. Vincenz-Krankenhaus Paderborn - Medizinische Klinik II
🇩🇪Paderborn, Germany
Royal Infirmary of Edinburgh
🇬🇧Edinburgh, United Kingdom
Taipei Veterans General Hospital
🇨🇳Taipei, Taiwan
L.T. Malaya Therapy National Institute of the National Academy of medical science of Ukraine
🇺🇦Kharkiv, Ukraine
Kyiv City Clinical Hospital 4
🇺🇦Kyiv, Ukraine
Lutsk City Hospital
🇺🇦Luts'k, Ukraine
Transcarpathian Regional Clinical Cardiology Clinic
🇺🇦Uzhhorod, Ukraine