title: Dual-antiplatelet treatment beyond 1 year after drug-eluting stent implantation (ARCTIC-Interruption): a randomised trial.
abstract: BACKGROUND
  Optimum duration of dual antiplatelet treatment (DAPT) after coronary stenting remains uncertain, with an unknown efficacy to safety ratio of extended treatment leading to discrepancies between international guidelines and clinical practice. We assessed whether DAPT continuation beyond 1 year after coronary stenting is beneficial.
  
  
  METHODS
  This analysis was a planned extension of the previously published ARCTIC-Monitoring trial, in which we randomly allocated 2440 patients to a strategy of platelet function testing with antiplatelet treatment adjustment or a conventional strategy after coronary stenting with drug-eluting stent (DES). We recruited patients (aged 18 years or older) scheduled for planned DES implantation at 38 centres in France. After 1 year of follow-up, patients without contraindication to interruption of DAPT were eligible for a second randomisation to this second phase of the study (ARCTIC-Interruption). Using a computer-generated randomisation sequence (1:1; stratified by centre), we allocated patients to a strategy of interruption of DAPT where the thienopyridine was interrupted and single aspirin antiplatelet treatment was maintained (interruption group) or a strategy of DAPT continuation for 6-18 months (continuation group). The primary endpoint was the composite of death, myocardial infarction, stent thrombosis, stroke, or urgent revascularisation, analysed by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00827411.
  
  
  RESULTS
  Between Jan 4, 2011, and March 3, 2012, 1259 eligible patients were randomly allocated to treatment in ARCTIC-Interruption: 624 to the interruption group and 635 to the continuation group. After a median follow-up of 17 months (IQR 15-18), the primary endpoint occurred in 27 (4%) patients in the interruption group and 24 (4%) patients in the continuation group (hazard ratio [HR] 1·17 [95% CI 0·68-2·03]; p=0·58). STEEPLE major bleeding events occurred more often in the continuation group (seven [1%] patients) compared with the interruption group (one [<0·5%] patient; HR 0·15 [0·02-1·20]; p=0·073). Major or minor bleedings were also more common in the continuation group compared with the interruption group (12 [2%] patients vs three [1%] patients; HR 0·26 [0·07-0·91]; p=0·04).
  
  
  CONCLUSIONS
  Our finding suggests no apparent benefit but instead harm with extension of DAPT beyond 1 year after stenting with DES when no event has occurred within the first year after stenting. No conclusion can be drawn for high-risk patients who could not be randomised. The consistency between findings from all trials of such interruption suggests the need for a reappraisal of guidelines for DAPT after coronary stenting towards shorter duration of treatment.
  
  
  BACKGROUND
  Allies in Cardiovascular Trials Initiatives and Organized Networks (ACTION Study Group), Fondation de France, Sanofi-Aventis, Cordis, Medtronic, Boston Scientific, Fondation SGAM.
authors.affiliation: ACTION Study Group, Institut de Cardiologie Hôpital Pitié-Salpêtrière (APHP), Université Paris 6, INSERM, Paris, France.
authors.forename: Jean-Philippe
authors.initials: JP
authors.lastname: Collet
authors.affiliation: ACTION Study Group, Institut de Cardiologie Hôpital Pitié-Salpêtrière (APHP), Université Paris 6, INSERM, Paris, France.
authors.forename: Johanne
authors.initials: J
authors.lastname: Silvain
authors.affiliation: ACTION Study Group, Institut de Cardiologie Hôpital Pitié-Salpêtrière (APHP), Université Paris 6, INSERM, Paris, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Barthélémy
authors.affiliation: Les Hôpitaux de Chartres, Le Coudray, France.
authors.forename: Grégoire
authors.initials: G
authors.lastname: Rangé
authors.affiliation: ACTION Study Group, Cardiologie, CHU Carémeau, Nîmes, France.
authors.forename: Guillaume
authors.initials: G
authors.lastname: Cayla
authors.affiliation: CHRU de Lille, Lille, France.
authors.forename: Eric
authors.initials: E
authors.lastname: Van Belle
authors.affiliation: Département de Cardiologie, CHU La Timone, Marseille, France.
authors.forename: Thomas
authors.initials: T
authors.lastname: Cuisset
authors.affiliation: Cardiologie, CH de Lagny-Marne-la-Vallée, Lagny-sur-Marne, France.
authors.forename: Simon
authors.initials: S
authors.lastname: Elhadad
authors.affiliation: CHU Jean Minjoz, Besançon, France.
authors.forename: François
authors.initials: F
authors.lastname: Schiele
authors.affiliation: GH du Centre Alsace, France.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Lhoest
authors.affiliation: CHR Strasbourg, France.
authors.forename: Patrick
authors.initials: P
authors.lastname: Ohlmann
authors.affiliation: CHU Rangueil, Toulouse, France.
authors.forename: Didier
authors.initials: D
authors.lastname: Carrié
authors.affiliation: CHRU de Lille, Lille, France; ACTION Study Group, Unité de Recherche Clinique-Hôpital Lariboisière (APHP), and Université Denis Diderot, Paris, France.
authors.forename: Hélène
authors.initials: H
authors.lastname: Rousseau
authors.affiliation: Centre Hospitalier Bichat (APHP), Paris, France.
authors.forename: Pierre
authors.initials: P
authors.lastname: Aubry
authors.affiliation: Institut Mutualiste Montsouris, Paris, France.
authors.forename: Jacques
authors.initials: J
authors.lastname: Monségu
authors.affiliation: ACTION Study Group, Institut de Cardiologie Hôpital Pitié-Salpêtrière (APHP), Université Paris 6, INSERM, Paris, France.
authors.forename: Pierre
authors.initials: P
authors.lastname: Sabouret
authors.affiliation: ACTION Study Group, Institut de Cardiologie Hôpital Pitié-Salpêtrière (APHP), Université Paris 6, INSERM, Paris, France.
authors.forename: Stephen A
authors.initials: SA
authors.lastname: O'Connor
authors.affiliation: ACTION Study Group, Institut de Cardiologie Hôpital Pitié-Salpêtrière (APHP), Université Paris 6, INSERM, Paris, France.
authors.forename: Jérémie
authors.initials: J
authors.lastname: Abtan
authors.affiliation: ACTION Study Group, Institut de Cardiologie Hôpital Pitié-Salpêtrière (APHP), Université Paris 6, INSERM, Paris, France.
authors.forename: Mathieu
authors.initials: M
authors.lastname: Kerneis
authors.affiliation: CHU Trousseau, Tours, France.
authors.forename: Christophe
authors.initials: C
authors.lastname: Saint-Etienne
authors.affiliation: ACTION study Group, CHU Caen, France.
authors.forename: Farzin
authors.initials: F
authors.lastname: Beygui
authors.affiliation: ACTION Study Group, Unité de Recherche Clinique-Hôpital Lariboisière (APHP), and Université Denis Diderot, Paris, France.
authors.forename: Eric
authors.initials: E
authors.lastname: Vicaut
authors.affiliation: ACTION Study Group, Institut de Cardiologie Hôpital Pitié-Salpêtrière (APHP), Université Paris 6, INSERM, Paris, France. Electronic address: gilles.montalescot@psl.aphp.fr.
authors.forename: Gilles
authors.initials: G
authors.lastname: Montalescot
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001241:Aspirin / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D003324:Coronary Artery Disease / Q000628:therapy*; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D054855:Drug-Eluting Stents; D005260:Female; D006470:Hemorrhage / Q000139:chemically induced; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D062645:Percutaneous Coronary Intervention / Q000379:methods; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D010979:Platelet Function Tests / Q000379:methods; D011446:Prospective Studies; D011725:Pyridines / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D010975:Platelet Aggregation Inhibitors; D011725:Pyridines; C446540:thienopyridine; D001241:Aspirin