Clinical trial NCT01830543: A Study Exploring Two Strategies of Rivaroxaban (JNJ39039039; BAY-59-7939) and One of Oral Vitamin K Antagonist in Patients With Atrial Fibrillation Who Undergo Percutaneous Coronary Intervention
Official title: An Open-label, Randomized, Controlled, Multicenter Study Exploring Two Treatment Strategies of Rivaroxaban and a Dose-Adjusted Oral Vitamin K Antagonist Treatment Strategy in Subjects With Atrial Fibrillation Who Undergo Percutaneous Coronary Intervention
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Atrial Fibrillation
Percutaneous Coronary Intervention
Keywords: Atrial Fibrillation
Irregular heart beat
rivaroxaban
aspirin
clopidogrel
prasugrel
ticagrelor
vitamin K antagonist
Lead sponsor: Janssen Scientific Affairs, LLC
Sponsor class: INDUSTRY
Collaborators: name: Bayer
First posted: 2013-04-12
Enrollment: 2124
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The primary purpose of this study is to evaluate the safety for 2 different rivaroxaban treatment strategies and one Vitamin K Antagonist (VKA) treatment strategy utilizing various combinations of dual antiplatelet therapy (DAPT) or low-dose aspirin (ASA) or clopidogrel (or prasugrel or ticagrelor).

Detailed description: This is an open-label (both physician and participant know the treatment that the participant receives), randomized (study medication is assigned by chance), multicenter clinical study assessing the safety of 2 rivaroxaban treatment strategies and one vitamin K antagonist (VKA) treatment strategy in participants, who have paroxysmal, persistent, or permanent non-valvular atrial fibrillation (AF) and have had a percutaneous coronary intervention (PCI) with stent placement.

A target of 2,100 participants will be randomized into the study, with approximately 700 participants in each treatment strategy group. The randomization will be stratified by the intended duration of DAPT (1, 6, or 12 months).

The study consists of a screening phase, a 12-month open-label treatment phase, and an end-of-treatment/early withdrawal visit. The total duration of participation in the study for each participant is approximately 12 months.

Eligibility criteria: Inclusion Criteria:

* Have a documented medical history of paroxysmal, persistent, or permanent non-valvular atrial fibrillation (AF)
* Have undergone percutaneous coronary intervention (PCI) procedure (with stent placement) for primary atherosclerotic disease
* Must have an international normalized ratio (INR) of 2.5 or below to be randomized
* Women must be postmenopausal before entry or practicing a highly effective method of birth control when heterosexually active
* Be willing and able to adhere to the prohibitions and restrictions specified in the study protocol

Exclusion Criteria:

* Have any condition that contraindicates anticoagulant or antiplatelet therapy or would have an unacceptable risk of bleeding, such as, but not limited to: platelet count \<90,000/microliter at screening, history of intracranial hemorrhage, 12 month history of clinically significant gastrointestinal bleeding, non-VKA induced elevated prothrombin time (PT) at screening
* Have anemia of unknown cause with a hemoglobin level \<10 g/dL (\<6.21 mmol/L)
* Have a history of stroke or Transient Ischemic Attack (TIA)
* Have a calculated Creatinine Clearance (CrCl) \<30 mL/min at screening
* Have known significant liver disease or liver function test (LFT) abnormalities
* Have any severe condition that would limit life expectancy to less than 12 months

Primary outcomes:
measure: Percentage of Participants With Clinically Significant Bleeding
timeFrame: Up to Month 12
Secondary outcomes:
measure: Percentage of Participants With Thrombolysis in Myocardial Infarction (TIMI) Major Bleeding
timeFrame: Up to Month 12 and end of DAPT-Month 1, 6 and 12
measure: Percentage of Participants With Thrombolysis in Myocardial Infarction (TIMI) Minor Bleeding
timeFrame: Up to Month 12 and end of DAPT-Month 1, 6 and 12
measure: Percentage of Participants With Bleeding Requiring Medical Attention (BRMA)
timeFrame: Up to Month 12 and end of DAPT-Month 1, 6 and 12
measure: Percentage of Participants With Composite of Adverse Cardiovascular Events (Cardiovascular Death, Myocardial Infarction (MI) and Stroke)
timeFrame: Up to Month 12 and end of DAPT-Month 1, 6 and 12
measure: Percentage of Participants With Cardiovascular Death
timeFrame: Up to Month 12 and end of DAPT-Month 1, 6 and 12
measure: Percentage of Participants With Myocardial Infarction
timeFrame: Up to Month 12 and end of DAPT-Month 1, 6 and 12
measure: Percentage of Participants With Stroke
timeFrame: Up to Month 12 and end of DAPT-Month 1, 6 and 12
measure: Percentage of Participants With Stent Thrombosis
timeFrame: Up to Month 12 and end of DAPT-Month 1, 6 and 12
Other outcomes:
Locations:
city: Huntsville
country: United States
state: Alabama
city: Los Alamitos
country: United States
state: California
city: Mission Viejo
country: United States
state: California
city: Oceanside
country: United States
state: California
city: Riverside
country: United States
state: California
city: Sacramento
country: United States
state: California
city: San Francisco
country: United States
state: California
city: Stockton
country: United States
state: California
city: Thousand Oaks
country: United States
state: California
city: Torrance
country: United States
state: California
city: Colorado Springs
country: United States
state: Colorado
city: Lakewood
country: United States
state: Colorado
city: Littleton
country: United States
state: Colorado
city: Danbury
country: United States
state: Connecticut
city: Washington, D.C.
country: United States
state: District of Columbia
city: Atlantis
country: United States
state: Florida
city: Clearwater
country: United States
state: Florida
city: Daytona Beach
country: United States
state: Florida
city: Jacksonville
country: United States
state: Florida
city: Port Charlotte
country: United States
state: Florida
city: Safety Harbor
country: United States
state: Florida
city: Saint Petersburg
country: United States
state: Florida
city: Tallahassee
country: United States
state: Florida
city: Tampa
country: United States
state: Florida
city: Columbus
country: United States
state: Georgia
city: Macon
country: United States
state: Georgia
city: Marietta
country: United States
state: Georgia
city: Boise
country: United States
state: Idaho
city: Hazel Crest
country: United States
state: Illinois
city: Indianapolis
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state: Indiana
city: Munster
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state: Indiana
city: Hammond
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state: Louisiana
city: Lake Charles
country: United States
state: Louisiana
city: Slidell
country: United States
state: Louisiana
city: Auburn
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state: Maine
city: Bangor
country: United States
state: Maine
city: Baltimore
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state: Maryland
city: Detroit
country: United States
state: Michigan
city: Lansing
country: United States
state: Michigan
city: Mount Clemens
country: United States
state: Michigan
city: Petoskey
country: United States
state: Michigan
city: Ypsilanti
country: United States
state: Michigan
city: Kansas City
country: United States
state: Missouri
city: Saint Louis
country: United States
state: Missouri
city: Kalispell
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state: Montana
city: Las Vegas
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state: Nevada
city: Hackensack
country: United States
state: New Jersey
city: Haddon Heights
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state: New Jersey
city: New Brunswick
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state: New Jersey
city: Newark
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state: New Jersey
city: Ridgewood
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city: Albuquerque
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state: New Mexico
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state: Oklahoma
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state: Oklahoma
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state: Oregon
city: Portland
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state: Oregon
city: Abington
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state: Pennsylvania
city: Camp Hill
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state: Pennsylvania
city: Doylestown
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state: Pennsylvania
city: Erie
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state: Pennsylvania
city: Philadelphia
country: United States
state: Pennsylvania
city: Sayre
country: United States
state: Pennsylvania
city: York
country: United States
state: Pennsylvania
city: Greenville
country: United States
state: South Carolina
city: Mount Pleasant
country: United States
state: South Carolina
city: Rapid City
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state: South Dakota
city: Jackson
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state: Tennessee
city: Knoxville
country: United States
state: Tennessee
city: Austin
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state: Texas
city: Fort Worth
country: United States
state: Texas
city: Humble
country: United States
state: Texas
city: Odessa
country: United States
state: Texas
city: Plano
country: United States
state: Texas
city: Layton
country: United States
state: Utah
city: Charlottesville
country: United States
state: Virginia
city: Manassas
country: United States
state: Virginia
city: Midlothian
country: United States
state: Virginia
city: Richmond
country: United States
state: Virginia
city: Bellevue
country: United States
state: Washington
city: Seattle
country: United States
state: Washington
city: Milwaukee
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state: Wisconsin
city: Weston
country: United States
state: Wisconsin
city: Bahia Blanca
country: Argentina
city: Buenos Aires
country: Argentina
city: C.a.b.a.
country: Argentina
city: Cordoba
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city: Corrientes
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city: La Plata
country: Argentina
city: Resistencia
country: Argentina
city: Rosario
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city: Santa Fe
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city: Vicente Lopez
country: Argentina
city: Chermside N/A
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city: Epping
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city: Hobart
country: Australia
city: Kogarah
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city: Liverpool
country: Australia
city: New Lambton
country: Australia
city: Wollongong
country: Australia
city: Aalst
country: Belgium
city: Bonheiden
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city: Brasschaat
country: Belgium
city: Brugge
country: Belgium
city: Bruxelles
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city: Genk
country: Belgium
city: Gent
country: Belgium
city: Liège
country: Belgium
city: Mechelen
country: Belgium
city: Mol
country: Belgium
city: Roeselare
country: Belgium
city: Turnhout
country: Belgium
city: Belo Horizonte
country: Brazil
city: Blumenau
country: Brazil
city: Brasilia
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city: Campina Grande Do Sul
country: Brazil
city: Campinas
country: Brazil
city: Curitiba
country: Brazil
city: Marilia
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city: Passo Fundo
country: Brazil
city: Porto Alegre
country: Brazil
city: Recife
country: Brazil
city: Sao Paulo
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city: São José Do Rio Preto
country: Brazil
city: São Paulo
country: Brazil
city: Uberlandia
country: Brazil
city: Votuporanga
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city: Blagoevgrad
country: Bulgaria
city: Burgas
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city: Pazardjik
country: Bulgaria
city: Pleven
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city: Sofia
country: Bulgaria
city: Varna
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city: Veliko Tarnovo
country: Bulgaria
city: Edmonton
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state: Alberta
city: Maple Ridge
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state: British Columbia
city: New Westminster
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state: British Columbia
city: Vancouver
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state: British Columbia
city: Victoria
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state: British Columbia
city: St. John'S
country: Canada
state: Newfoundland and Labrador
city: London
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state: Ontario
city: Ottawa
country: Canada
state: Ontario
city: Sudbury
country: Canada
state: Ontario
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country: Canada
state: Ontario
city: Montreal
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state: Quebec
city: Sherbrooke
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city: Chicoutimi
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city: Saint John
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city: Alto
country: Chile
city: Concepcion
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city: Punta Arenas
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city: Santiago
country: Chile
city: Temuco
country: Chile
city: Brno 2
country: Czechia
city: Brno
country: Czechia
city: Hradec Kralove
country: Czechia
city: Jablonec Na Nisou
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city: Karlovy Vary
country: Czechia
city: Kladno
country: Czechia
city: Litomysl
country: Czechia
city: Olomouc
country: Czechia
city: Plzen
country: Czechia
city: Praha 10 N/A
country: Czechia
city: Praha 2
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city: Praha
country: Czechia
city: Slany
country: Czechia
city: Uherske Hradiste
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city: Herning
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city: Roskilde
country: Denmark
city: Svendborg N/A
country: Denmark
city: Vejle
country: Denmark
city: Besancon Cedex Franche-Comté
country: France
city: Caen Cedex 9
country: France
city: Centres
country: France
city: Chartres
country: France
city: Lille
country: France
city: Limoges Cedex
country: France
city: Marseille Cedex 05
country: France
city: Montfermeil
country: France
city: Nantes Cedex 1
country: France
city: Nimes
country: France
city: Paris 75
country: France
city: Paris
country: France
city: Pau
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city: Pessac
country: France
city: Poitiers
country: France
city: Toulouse
country: France
city: Bad Friedrichshall
country: Germany
city: Bad Nauheim
country: Germany
city: Berlin
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city: Dresden
country: Germany
city: Esslingen
country: Germany
city: Frankfurt Am Main
country: Germany
city: Freiburg
country: Germany
city: Greifswald
country: Germany
city: Göttingen
country: Germany
city: Hamburg
country: Germany
city: Heidelberg
country: Germany
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country: Germany
city: Limburg
country: Germany
city: Mannheim
country: Germany
city: Ulm
country: Germany
city: Witten
country: Germany
city: Busan
country: Korea, Republic of
city: Daejeon
country: Korea, Republic of
city: Gyeonggi-Do
country: Korea, Republic of
city: Incheon
country: Korea, Republic of
city: Seongnam
country: Korea, Republic of
city: Seoul
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city: Uden
country: Netherlands
city: Bedzin
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city: Bielsko-Biala
country: Poland
city: Chrzanow
country: Poland
city: Gdynia
country: Poland
city: Grodzisk Mazowiecki
country: Poland
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country: Poland
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country: Poland
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country: Poland
city: Mielec
country: Poland
city: Nowy Targ
country: Poland
city: Ostrowiec Swietokrzyski
country: Poland
city: Oswiecim
country: Poland
city: Plock
country: Poland
city: Rzeszow Poland
country: Poland
city: Starachowice
country: Poland
city: Starogard Gdanski
country: Poland
city: Szczecin
country: Poland
city: Torun
country: Poland
city: Tychy
country: Poland
city: Ustron
country: Poland
city: Warszawa
country: Poland
city: Zamosc
country: Poland
city: Bucharest
country: Romania
city: Bucuresti
country: Romania
city: Cluj Napoca
country: Romania
city: Targu-Mures
country: Romania
city: Tg Mures
country: Romania
city: Arkhangelsk
country: Russian Federation
city: Barnaul
country: Russian Federation
city: Chita
country: Russian Federation
city: Ekaterinburg
country: Russian Federation
city: Kemerovo
country: Russian Federation
city: Krasnodar
country: Russian Federation
city: Krasnoyarsk
country: Russian Federation
city: Moscow
country: Russian Federation
city: Nizhny Novgorod
country: Russian Federation
city: Perm
country: Russian Federation
city: Rostov On Don
country: Russian Federation
city: Samara
country: Russian Federation
city: Saratov
country: Russian Federation
city: St. Petersburg
country: Russian Federation
city: Syktyvkar
country: Russian Federation
city: Tumen
country: Russian Federation
city: Tyumen
country: Russian Federation
city: Cape Town
country: South Africa
city: Centurion
country: South Africa
city: Linksfield West, Johannesburg
country: South Africa
city: Somerset West
country: South Africa
city: Falun
country: Sweden
city: Göteborg
country: Sweden
city: Jönköping
country: Sweden
city: Lund
country: Sweden
city: Malmö
country: Sweden
city: Stockholm N/A
country: Sweden
city: Stockholm
country: Sweden
city: Umeå
country: Sweden
city: Örebro
country: Sweden
city: Kaohsiung
country: Taiwan
city: Taichung
country: Taiwan
city: Tainan
country: Taiwan
city: Taipei
country: Taiwan
city: Taoyuan
country: Taiwan
city: Ankara
country: Turkey
city: Antalya
country: Turkey
city: Bursa
country: Turkey
city: Gaziantep
country: Turkey
city: Istanbul Nap
country: Turkey
city: Istanbul
country: Turkey
city: Izmir
country: Turkey
city: Kayseri
country: Turkey
city: Sivas
country: Turkey
city: Cherkassy
country: Ukraine
city: Dnepropetrovsk
country: Ukraine
city: Ivano-Frankivsk
country: Ukraine
city: Kharkiv
country: Ukraine
city: Kharkov
country: Ukraine
city: Khemelnitskiy
country: Ukraine
city: Kyiv
country: Ukraine
city: Lviv
country: Ukraine
city: Odessa
country: Ukraine
city: Rivne
country: Ukraine
city: Uzhgorod
country: Ukraine
city: Zaporizhzhya
country: Ukraine
city: Bath
country: United Kingdom
city: Birmingham
country: United Kingdom
city: Blackburn
country: United Kingdom
city: Bradford
country: United Kingdom
city: Clydebank
country: United Kingdom
city: Cottingham
country: United Kingdom
city: Coventry
country: United Kingdom
city: Dorchester
country: United Kingdom
city: Dundee
country: United Kingdom
city: Edinburgh
country: United Kingdom
city: Exeter
country: United Kingdom
city: Hampshire
country: United Kingdom
city: Harrow
country: United Kingdom
city: High Wycombe
country: United Kingdom
city: London
country: United Kingdom
city: Middlesbrough N/A
country: United Kingdom
city: Norwich
country: United Kingdom
city: Nottingham
country: United Kingdom
city: Plymouth
country: United Kingdom
city: Portsmouth
country: United Kingdom
city: Torquay
country: United Kingdom
city: Truro
country: United Kingdom
city: Worcester
country: United Kingdom
Study officials:
affiliation: Janssen Scientific Affairs, LLC
name: Janssen Scientific Affairs, LLC Clinical Trial
role: STUDY_DIRECTOR
References:
citation: Kerneis M, Yee MK, Mehran R, Nafee T, Bode C, Halperin JL, Peterson ED, Verheugt FWA, Wildgoose P, van Eickels M, Lip GYH, Cohen M, Fox KAA, Gibson CM. Novel Oral Anticoagulant Based Versus Vitamin K Antagonist Based Double Therapy Among Stented Patients With Atrial Fibrillation: Insights From the PIONEER AF-PCI Trial. Circ Cardiovasc Interv. 2019 Nov;12(11):e008160. doi: 10.1161/CIRCINTERVENTIONS.119.008160. Epub 2019 Nov 11.
citation: Gibson WJ, Nafee T, Travis R, Yee M, Kerneis M, Ohman M, Gibson CM. Machine learning versus traditional risk stratification methods in acute coronary syndrome: a pooled randomized clinical trial analysis. J Thromb Thrombolysis. 2020 Jan;49(1):1-9. doi: 10.1007/s11239-019-01940-8.
citation: Kerneis M, Yee MK, Mehran R, Nafee T, Bode C, Halperin JL, Peterson ED, Verheugt FWA, Wildgoose P, van Eickels M, Lip GYH, Cohen M, Fox KAA, Gibson CM. Association of International Normalized Ratio Stability and Bleeding Outcomes Among Atrial Fibrillation Patients Undergoing Percutaneous Coronary Intervention. Circ Cardiovasc Interv. 2019 Feb;12(2):e007124. doi: 10.1161/CIRCINTERVENTIONS.118.007124.
citation: Chi G, Kerneis M, Kalayci A, Liu Y, Mehran R, Bode C, Halperin JL, Verheugt FWA, Wildgoose P, van Eickels M, Lip GYH, Cohen M, Peterson ED, Fox KAA, Gibson CM. Safety and efficacy of non-vitamin K oral anticoagulant for atrial fibrillation patients after percutaneous coronary intervention: A bivariate analysis of the PIONEER AF-PCI and RE-DUAL PCI trial. Am Heart J. 2018 Sep;203:17-24. doi: 10.1016/j.ahj.2018.06.003. Epub 2018 Jun 13.
citation: Chi G, Yee MK, Kalayci A, Kerneis M, AlKhalfan F, Mehran R, Bode C, Halperin JL, Verheugt FWA, Wildgoose P, van Eickels M, Lip GYH, Cohen M, Peterson ED, Fox KAA, Gibson CM. Total bleeding with rivaroxaban versus warfarin in patients with atrial fibrillation receiving antiplatelet therapy after percutaneous coronary intervention. J Thromb Thrombolysis. 2018 Oct;46(3):346-350. doi: 10.1007/s11239-018-1703-5.
citation: Kerneis M, Gibson CM, Chi G, Mehran R, AlKhalfan F, Talib U, Pahlavani S, Mir M, Bode C, Halperin JL, Nafee T, Peterson ED, Verheugt FWA, Wildgoose P, van Eickels M, Lip GYH, Fox KAA, Cohen M. Effect of Procedure and Coronary Lesion Characteristics on Clinical Outcomes Among Atrial Fibrillation Patients Undergoing Percutaneous Coronary Intervention: Insights From the PIONEER AF-PCI Trial. JACC Cardiovasc Interv. 2018 Apr 9;11(7):626-634. doi: 10.1016/j.jcin.2017.11.009. Epub 2018 Mar 14.
citation: Gibson CM, Mehran R, Bode C, Halperin J, Verheugt FW, Wildgoose P, Birmingham M, Ianus J, Burton P, van Eickels M, Korjian S, Daaboul Y, Lip GY, Cohen M, Husted S, Peterson ED, Fox KA. Prevention of Bleeding in Patients with Atrial Fibrillation Undergoing PCI. N Engl J Med. 2016 Dec 22;375(25):2423-2434. doi: 10.1056/NEJMoa1611594. Epub 2016 Nov 14.
citation: Gibson CM, Pinto DS, Chi G, Arbetter D, Yee M, Mehran R, Bode C, Halperin J, Verheugt FW, Wildgoose P, Burton P, van Eickels M, Korjian S, Daaboul Y, Jain P, Lip GY, Cohen M, Peterson ED, Fox KA. Recurrent Hospitalization Among Patients With Atrial Fibrillation Undergoing Intracoronary Stenting Treated With 2 Treatment Strategies of Rivaroxaban or a Dose-Adjusted Oral Vitamin K Antagonist Treatment Strategy. Circulation. 2017 Jan 24;135(4):323-333. doi: 10.1161/CIRCULATIONAHA.116.025783. Epub 2016 Nov 14.
citation: Gibson CM, Mehran R, Bode C, Halperin J, Verheugt F, Wildgoose P, van Eickels M, Lip GY, Cohen M, Husted S, Peterson E, Fox K. An open-label, randomized, controlled, multicenter study exploring two treatment strategies of rivaroxaban and a dose-adjusted oral vitamin K antagonist treatment strategy in subjects with atrial fibrillation who undergo percutaneous coronary intervention (PIONEER AF-PCI). Am Heart J. 2015 Apr;169(4):472-8.e5. doi: 10.1016/j.ahj.2014.12.006. Epub 2014 Dec 20.