Jean-Philippe Collet1, Johanne Silvain1, Olivier Barthélémy1, Grégoire Rangé2, Guillaume Cayla3, Eric Van Belle4, Thomas Cuisset5, Simon Elhadad6, François Schiele7, Nicolas Lhoest8, Patrick Ohlmann9, Didier Carrié10, Hélène Rousseau11, Pierre Aubry12, Jacques Monségu13, Pierre Sabouret1, Stephen A O'Connor1, Jérémie Abtan1, Mathieu Kerneis1, Christophe Saint-Etienne14, Farzin Beygui15, Eric Vicaut16, Gilles Montalescot17. 1. ACTION Study Group, Institut de Cardiologie Hôpital Pitié-Salpêtrière (APHP), Université Paris 6, INSERM, Paris, France. 2. Les Hôpitaux de Chartres, Le Coudray, France. 3. ACTION Study Group, Cardiologie, CHU Carémeau, Nîmes, France. 4. CHRU de Lille, Lille, France. 5. Département de Cardiologie, CHU La Timone, Marseille, France. 6. Cardiologie, CH de Lagny-Marne-la-Vallée, Lagny-sur-Marne, France. 7. CHU Jean Minjoz, Besançon, France. 8. GH du Centre Alsace, France. 9. CHR Strasbourg, France. 10. CHU Rangueil, Toulouse, France. 11. CHRU de Lille, Lille, France; ACTION Study Group, Unité de Recherche Clinique-Hôpital Lariboisière (APHP), and Université Denis Diderot, Paris, France. 12. Centre Hospitalier Bichat (APHP), Paris, France. 13. Institut Mutualiste Montsouris, Paris, France. 14. CHU Trousseau, Tours, France. 15. ACTION study Group, CHU Caen, France. 16. ACTION Study Group, Unité de Recherche Clinique-Hôpital Lariboisière (APHP), and Université Denis Diderot, Paris, France. 17. ACTION Study Group, Institut de Cardiologie Hôpital Pitié-Salpêtrière (APHP), Université Paris 6, INSERM, Paris, France. Electronic address: gilles.montalescot@psl.aphp.fr.
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 forplanned DES implantationat 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. FINDINGS: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). INTERPRETATION: 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. FUNDING: Allies in Cardiovascular Trials Initiatives and Organized Networks (ACTION Study Group), Fondation de France, Sanofi-Aventis, Cordis, Medtronic, Boston Scientific, Fondation SGAM.
RCT Entities:
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. FINDINGS: 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). INTERPRETATION: 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. FUNDING: Allies in Cardiovascular Trials Initiatives and Organized Networks (ACTION Study Group), Fondation de France, Sanofi-Aventis, Cordis, Medtronic, Boston Scientific, Fondation SGAM.
Authors: Laura Mauri; Dean J Kereiakes; Robert W Yeh; Priscilla Driscoll-Shempp; Donald E Cutlip; P Gabriel Steg; Sharon-Lise T Normand; Eugene Braunwald; Stephen D Wiviott; David J Cohen; David R Holmes; Mitchell W Krucoff; James Hermiller; Harold L Dauerman; Daniel I Simon; David E Kandzari; Kirk N Garratt; David P Lee; Thomas K Pow; Peter Ver Lee; Michael J Rinaldi; Joseph M Massaro Journal: N Engl J Med Date: 2014-11-16 Impact factor: 91.245
Authors: Christopher R Kelly; Ajay J Kirtane; Jennifer Stant; Gregg W Stone; Robert M Minutello; S Chiu Wong; Honeyleen Manuzon; Roxanne Gerow-Smith; Nancy Kelley; LeRoy E Rabbani Journal: Crit Pathw Cardiol Date: 2017-03