title: Rationale and design of POPular-TAVI: antiPlatelet therapy fOr Patients undergoing Transcatheter Aortic Valve Implantation.
abstract: BACKGROUND
  Despite improving experience and techniques, ischemic and bleeding complications after transcatheter aortic valve implantation (TAVI) remain prevalent and impair survival. Current guidelines recommend the temporary addition of clopidogrel in the initial period after TAVI to prevent thromboembolic events. However, explorative studies suggest that this is associated with a higher rate of major bleeding without a decrease in thromboembolic complications.
  
  
  METHODS
  The POPular TAVI trial is a prospective randomized, controlled, open-label multicenter clinical trial to test the hypothesis that monotherapy with aspirin or oral anticoagulation (OAC) after TAVI is safer than the addition of clopidogrel for 3 months, without compromising clinical benefit. This trial encompasses 2 cohorts: cohort A, patients are randomized 1:1 to aspirin vs aspirin + clopidogrel, and cohort B, patients on OAC therapy are randomized 1:1 to OAC vs OAC + clopidogrel. Primary outcome is freedom from non-procedure-related bleeding at 1 year. Secondary net-clinical benefit outcome is freedom from the composite of cardiovascular death, non-procedural-related bleeding, myocardial infarction, or stroke at 1 year. The primary outcome is analyzed for superiority, whereas the secondary outcome is analyzed for noninferiority. Recruitment began in February 2014, and the trial will continue until a total of 1,000 patients (684 expected in cohort A and 316 in cohort B) are included and followed up for 1 year.
  
  
  CONCLUSIONS
  The POPular TAVI trial (NCT02247128) is the first large randomized controlled trial to test if monotherapy with aspirin or OAC vs additional clopidogrel after TAVI reduces bleeding with a favorable net-clinical benefit.
authors.affiliation: Department of Cardiology, St Antonius Hospital, Nieuwegein, the Netherlands.
authors.forename: Vincent Johan
authors.initials: VJ
authors.lastname: Nijenhuis
authors.affiliation: Department of Cardiology, St Antonius Hospital, Nieuwegein, the Netherlands.
authors.forename: Naoual
authors.initials: N
authors.lastname: Bennaghmouch
authors.affiliation: Department of Cardiology, Academic Medical Centre, Amsterdam, the Netherlands.
authors.forename: Mariella
authors.initials: M
authors.lastname: Hassell
authors.affiliation: Department of Cardiology, Academic Medical Centre, Amsterdam, the Netherlands.
authors.forename: Jan
authors.initials: J
authors.lastname: Baan
authors.affiliation: Department of Cardiology, St Antonius Hospital, Nieuwegein, the Netherlands.
authors.forename: Jan Peter
authors.initials: JP
authors.lastname: van Kuijk
authors.affiliation: Department of Cardiology, St Antonius Hospital, Nieuwegein, the Netherlands.
authors.forename: Pierfrancesco
authors.initials: P
authors.lastname: Agostoni
authors.affiliation: Department of Cardiology, Isala Klinieken, Zwolle, the Netherlands.
authors.forename: Arnoud
authors.initials: A
authors.lastname: van 't Hof
authors.affiliation: Department of Cardiology, University Medical Centre St Radboud, Nijmegen, the Netherlands.
authors.forename: Peter C
authors.initials: PC
authors.lastname: Kievit
authors.affiliation: Department of Cardiology, Medical University Centre, Maastricht, the Netherlands.
authors.forename: Leo
authors.initials: L
authors.lastname: Veenstra
authors.affiliation: Department of Cardiology, University Medical Centre, Groningen, the Netherlands.
authors.forename: Pim
authors.initials: P
authors.lastname: van der Harst
authors.affiliation: Department of Cardiology, University Medical Centre, Groningen, the Netherlands.
authors.forename: Ad F M
authors.initials: AF
authors.lastname: van den Heuvel
authors.affiliation: Department of Cardiology, Amphia Hospital, Breda, the Netherlands.
authors.forename: Peter
authors.initials: P
authors.lastname: den Heijer
authors.affiliation: Department of Cardiology, St Antonius Hospital, Nieuwegein, the Netherlands.
authors.forename: Johannes C
authors.initials: JC
authors.lastname: Kelder
authors.affiliation: Department of Clinical Pharmacy, St Antonius Hospital, Nieuwegein, the Netherlands.
authors.forename: Vera H
authors.initials: VH
authors.lastname: Deneer
authors.affiliation: Department of Cardiology, University Medical Centre, Leiden, the Netherlands.
authors.forename: Frank
authors.initials: F
authors.lastname: van der Kley
authors.affiliation: Department of Cardiac Surgery, University of Verona, Verona, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Onorati
authors.affiliation: Department of Cardiology, Hôpital Universitaire Pitié Salpêtrière, Paris, France.
authors.forename: Jean Philippe
authors.initials: JP
authors.lastname: Collet
authors.affiliation: Department of Cardiovascular Surgery, UniversitätsSpital Zürich, Zürich, Switzerland.
authors.forename: Francesco
authors.initials: F
authors.lastname: Maisano
authors.affiliation: Department of Cardiology, Università Vita-Salute San Raffaele Milano, Milan, Italy.
authors.forename: Azeem
authors.initials: A
authors.lastname: Latib
authors.affiliation: Department of Cardiology, Wilhelminenspital, Vienna, Austria.
authors.forename: Kurt
authors.initials: K
authors.lastname: Huber
authors.affiliation: Department of Cardiology, University Medical Centre Utrecht, Utrecht, the Netherlands.
authors.forename: Pieter R
authors.initials: PR
authors.lastname: Stella
authors.affiliation: Department of Cardiology, St Antonius Hospital, Nieuwegein, the Netherlands. Electronic address: j.ten.berg@antoniusziekenhuis.nl.
authors.forename: Jurrien M
authors.initials: JM
authors.lastname: Ten Berg
mesh_terms: D000284:Administration, Oral; D001024:Aortic Valve Stenosis / Q000601:surgery; D001241:Aspirin / Q000008:administration & dosage*; D000077144:Clopidogrel; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D005060:Europe / Q000453:epidemiology; D005500:Follow-Up Studies; D006801:Humans; D015994:Incidence; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage; D011183:Postoperative Complications / Q000453:epidemiology / Q000517:prevention & control*; D011300:Preoperative Care / Q000379:methods*; D011446:Prospective Studies; D015996:Survival Rate / Q000639:trends; D013923:Thromboembolism / Q000453:epidemiology / Q000517:prevention & control*; D013988:Ticlopidine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D013997:Time Factors; D065467:Transcatheter Aortic Valve Replacement / Q000009:adverse effects*; D016896:Treatment Outcome
chemical_list: D010975:Platelet Aggregation Inhibitors; D000077144:Clopidogrel; D013988:Ticlopidine; D001241:Aspirin