title: Platelet function monitoring to adjust antiplatelet therapy in elderly patients stented for an acute coronary syndrome (ANTARCTIC): an open-label, blinded-endpoint, randomised controlled superiority trial.
abstract: Elderly patients are at high risk of ischaemic and bleeding events. Platelet function monitoring offers the possibility to individualise antiplatelet therapy to improve the therapeutic risk-benefit ratio. We aimed to assess the effect of platelet function monitoring with treatment adjustment in elderly patients stented for an acute coronary syndrome.
  
  
  
  We did this multicentre, open-label, blinded-endpoint, randomised controlled superiority study at 35 centres in France. Patients aged 75 years or older who had undergone coronary stenting for acute coronary syndrome were randomly assigned (1:1), via a central interactive voice-response system based on a computer-generated permuted-block randomisation schedule with randomly selected block sizes, to receive oral prasugrel 5 mg daily with dose or drug adjustment in case of inadequate response (monitoring group) or oral prasugrel 5 mg daily with no monitoring or treatment adjustment (conventional group). Randomisation was stratified by centre. Platelet function testing was done 14 days after randomisation and repeated 14 days after treatment adjustment in patients in the monitoring group. Study investigators and patients were not masked to treatment allocation, but allocation was concealed from an independent clinical events committee responsible for endpoint adjudication. The primary endpoint was a composite of cardiovascular death, myocardial infarction, stroke, stent thrombosis, urgent revascularisation, and Bleeding Academic Research Consortium-defined bleeding complications (types 2, 3, or 5) at 12 months' follow-up. We did analysis by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT01538446.
  
  
  
  Between March 27, 2012, and May 19, 2015, we randomly assigned 877 patients to the monitoring group (n=442) or the conventional group (n=435). The primary endpoint occurred in 120 (28%) patients in the monitoring group compared with 123 (28%) patients in the conventional group (hazard ratio [HR], 1·003, 95% CI 0·78-1·29; p=0·98). Rates of bleeding events did not differ significantly between groups.
  
  
  
  Platelet function monitoring with treatment adjustment did not improve the clinical outcome of elderly patients treated with coronary stenting for an acute coronary syndrome. Platelet function testing is still being used in many centres and international guidelines still recommend platelet function testing in high-risk situations. Our study does not support this practice or these recommendations.
  
  
  
  Eli Lilly and Company, Daiichi Sankyo, Stentys, Accriva Diagnostics, Medtronic, and Fondation Coeur et Recherche.
authors: ACTION Study Group, Service de Cardiologie, Centre Hospitalier Universitaire de Nimes, Université de Montpellier, Nimes, France.
authors: Guillaume
authors: G
authors: Cayla
authors: Department of Cardiology, Centre Hospitalier Universitaire Timone, Marseille, France; INSERM UMR1062, INRA UMR1260, Nutrition, Obesity and Risk of Thrombosis, Faculty of Medicine, Aix-Marseille University, Marseille, France.
authors: Thomas
authors: T
authors: Cuisset
authors: Sorbonne Université-Paris 06, ACTION Study Group, INSERM UMRS 1166, Institut de Cardiologie, Hôpital Pitié-Salpêtrière (AP-HP), Paris, France.
authors: Johanne
authors: J
authors: Silvain
authors: Département de Cardiologie, Centre Hospitalier Universitaire Montpellier, Montpellier, France.
authors: Florence
authors: F
authors: Leclercq
authors: Service de Cardiologie, Hôpital Lariboisière, Paris, France.
authors: Stephane
authors: S
authors: Manzo-Silberman
authors: Service de Cardiologie, Centre Hospitalier Universitaire Tours, Tours, France.
authors: Christophe
authors: C
authors: Saint-Etienne
authors: Hôpital Francois Mitterrand, Centre Hospitalier de Pau, Pau, France.
authors: Nicolas
authors: N
authors: Delarche
authors: ACTION Study Group, Service de Cardiologie, Centre Hospitalier d'Antibes-Juans-Les-Pins, Antibes, France.
authors: Anne
authors: A
authors: Bellemain-Appaix
authors: Service de Cardiologie, Les Hôpitaux de Chartres, Le Coudray, Chartres, France.
authors: Grégoire
authors: G
authors: Range
authors: Hôpital Ambroise Paré, Boulogne-Billancourt, France.
authors: Rami
authors: R
authors: El Mahmoud
authors: Service de Cardiologie, Centre Hospitalier Universitaire Toulouse, Toulouse, France.
authors: Didier
authors: D
authors: Carrié
authors: Service de Cardiologie, Centre Hospitalier d'Annecy, Annecy, France.
authors: Loic
authors: L
authors: Belle
authors: Service de Cardiologie, Centre Hospitalier Universitaire Clermont-Ferrand, Clermont-Ferrand, France.
authors: Geraud
authors: G
authors: Souteyrand
authors: Service de Cardiologie, Hôpital Bichat Claude Bernard, Paris, France.
authors: Pierre
authors: P
authors: Aubry
authors: Sorbonne Université-Paris 06, ACTION Study Group, INSERM UMRS 1166, Institut de Cardiologie, Hôpital Pitié-Salpêtrière (AP-HP), Paris, France.
authors: Pierre
authors: P
authors: Sabouret
authors: Service de Cardiologie, Hôpital Bichat Claude Bernard, Paris, France.
authors: Xavier Halna
authors: XH
authors: du Fretay
authors: ACTION Study Group, Service de Cardiologie, Centre Hospitalier Universitaire de Caen, Caen, France.
authors: Farzin
authors: F
authors: Beygui
authors: Department of Cardiology, Centre Hospitalier Universitaire Timone, Marseille, France; INSERM UMR1062, INRA UMR1260, Nutrition, Obesity and Risk of Thrombosis, Faculty of Medicine, Aix-Marseille University, Marseille, France.
authors: Jean-Louis
authors: JL
authors: Bonnet
authors: ACTION Study Group, Service de Cardiologie, Centre Hospitalier Universitaire de Nimes, Université de Montpellier, Nimes, France.
authors: Benoit
authors: B
authors: Lattuca
authors: Clinique Sainte Clotilde, Saint Denis de La Réunion, La Réunion, France.
authors: Christophe
authors: C
authors: Pouillot
authors: Service de Cardiologie, Hôpital Cochin, Paris, France.
authors: Olivier
authors: O
authors: Varenne
authors: Service de Cardiologie de Bastia, Centre Hospitalier de Bastia, Bastia, France.
authors: Ziad
authors: Z
authors: Boueri
authors: Service de Cardiologie, Centre Hospitalier Universitaire de Lille, Lille, France.
authors: Eric
authors: E
authors: Van Belle
authors: Service de Cardiologie, Hôpital Lariboisière, Paris, France.
authors: Patrick
authors: P
authors: Henry
authors: Service de Cardiologie, Centre Hospitalier Universitaire Clermont-Ferrand, Clermont-Ferrand, France.
authors: Pascal
authors: P
authors: Motreff
authors: Centre Hospitalier de Lagny Marne la Vallée, Jossigny, France.
authors: Simon
authors: S
authors: Elhadad
authors: Department of Pharmacology, CIC-1421, INSERM U1166-ICAN, Hôpital Pitié-Salpêtrière (AP-HP), Paris, France.
authors: Joe-Elie
authors: JE
authors: Salem
authors: Service de Cardiologie, Hôpital Bichat Claude Bernard, Paris, France.
authors: Jérémie
authors: J
authors: Abtan
authors: ACTION Study Group, Unité de Recherche Clinique, Lariboisière, Paris, France.
authors: Hélène
authors: H
authors: Rousseau
authors: Sorbonne Université-Paris 06, ACTION Study Group, INSERM UMRS 1166, Institut de Cardiologie, Hôpital Pitié-Salpêtrière (AP-HP), Paris, France.
authors: Jean-Philippe
authors: JP
authors: Collet
authors: ACTION Study Group, Unité de Recherche Clinique, Lariboisière, Paris, France.
authors: Eric
authors: E
authors: Vicaut
authors: Sorbonne Université-Paris 06, ACTION Study Group, INSERM UMRS 1166, Institut de Cardiologie, Hôpital Pitié-Salpêtrière (AP-HP), Paris, France. Electronic address: gilles.montalescot@aphp.fr.
authors: Gilles
authors: G
authors: Montalescot
mesh_terms: D054058:Acute Coronary Syndrome / Q000601:surgery* / Q000628:therapy; D000368:Aged; D000369:Aged, 80 and over; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D008297:Male; D008991:Monitoring, Physiologic; D062645:Percutaneous Coronary Intervention; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage*; D010979:Platelet Function Tests; D000068799:Prasugrel Hydrochloride / Q000008:administration & dosage*; D018570:Risk Assessment; D015607:Stents
chemical_list: D010975:Platelet Aggregation Inhibitors; D000068799:Prasugrel Hydrochloride