Guillaume Cayla1, Thomas Cuisset2, Johanne Silvain3, Florence Leclercq4, Stephane Manzo-Silberman5, Christophe Saint-Etienne6, Nicolas Delarche7, Anne Bellemain-Appaix8, Grégoire Range9, Rami El Mahmoud10, Didier Carrié11, Loic Belle12, Geraud Souteyrand13, Pierre Aubry14, Pierre Sabouret3, Xavier Halna du Fretay14, Farzin Beygui15, Jean-Louis Bonnet2, Benoit Lattuca1, Christophe Pouillot16, Olivier Varenne17, Ziad Boueri18, Eric Van Belle19, Patrick Henry5, Pascal Motreff13, Simon Elhadad20, Joe-Elie Salem21, Jérémie Abtan14, Hélène Rousseau22, Jean-Philippe Collet3, Eric Vicaut22, Gilles Montalescot23. 1. ACTION Study Group, Service de Cardiologie, Centre Hospitalier Universitaire de Nimes, Université de Montpellier, Nimes, France. 2. 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. 3. Sorbonne Université-Paris 06, ACTION Study Group, INSERM UMRS 1166, Institut de Cardiologie, Hôpital Pitié-Salpêtrière (AP-HP), Paris, France. 4. Département de Cardiologie, Centre Hospitalier Universitaire Montpellier, Montpellier, France. 5. Service de Cardiologie, Hôpital Lariboisière, Paris, France. 6. Service de Cardiologie, Centre Hospitalier Universitaire Tours, Tours, France. 7. Hôpital Francois Mitterrand, Centre Hospitalier de Pau, Pau, France. 8. ACTION Study Group, Service de Cardiologie, Centre Hospitalier d'Antibes-Juans-Les-Pins, Antibes, France. 9. Service de Cardiologie, Les Hôpitaux de Chartres, Le Coudray, Chartres, France. 10. Hôpital Ambroise Paré, Boulogne-Billancourt, France. 11. Service de Cardiologie, Centre Hospitalier Universitaire Toulouse, Toulouse, France. 12. Service de Cardiologie, Centre Hospitalier d'Annecy, Annecy, France. 13. Service de Cardiologie, Centre Hospitalier Universitaire Clermont-Ferrand, Clermont-Ferrand, France. 14. Service de Cardiologie, Hôpital Bichat Claude Bernard, Paris, France. 15. ACTION Study Group, Service de Cardiologie, Centre Hospitalier Universitaire de Caen, Caen, France. 16. Clinique Sainte Clotilde, Saint Denis de La Réunion, La Réunion, France. 17. Service de Cardiologie, Hôpital Cochin, Paris, France. 18. Service de Cardiologie de Bastia, Centre Hospitalier de Bastia, Bastia, France. 19. Service de Cardiologie, Centre Hospitalier Universitaire de Lille, Lille, France. 20. Centre Hospitalier de Lagny Marne la Vallée, Jossigny, France. 21. Department of Pharmacology, CIC-1421, INSERM U1166-ICAN, Hôpital Pitié-Salpêtrière (AP-HP), Paris, France. 22. ACTION Study Group, Unité de Recherche Clinique, Lariboisière, Paris, France. 23. 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.
Abstract
BACKGROUND: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. METHODS: 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. FINDINGS: 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. INTERPRETATION: 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. FUNDING: Eli Lilly and Company, Daiichi Sankyo, Stentys, Accriva Diagnostics, Medtronic, and Fondation Coeur et Recherche.
RCT Entities:
BACKGROUND: 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. METHODS: 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. FINDINGS: 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. INTERPRETATION: 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. FUNDING: Eli Lilly and Company, Daiichi Sankyo, Stentys, Accriva Diagnostics, Medtronic, and Fondation Coeur et Recherche.
Authors: Paul W A Janssen; Thomas O Bergmeijer; Gert-Jan A Vos; Johannes C Kelder; Khalid Qaderdan; Thea C Godschalk; Nicoline J Breet; Vera H M Deneer; Christian M Hackeng; Jurriën M Ten Berg Journal: Eur J Clin Pharmacol Date: 2019-06-14 Impact factor: 2.953
Authors: Kirill Orlov; Dmitry Kislitsin; Nikolay Strelnikov; Vadim Berestov; Anton Gorbatykh; Timur Shayakhmetov; Pavel Seleznev; Anton Tasenko Journal: Interv Neuroradiol Date: 2018-01-29 Impact factor: 1.610
Authors: H M H Spronk; T Padro; J E Siland; J H Prochaska; J Winters; A C van der Wal; J J Posthuma; G Lowe; E d'Alessandro; P Wenzel; D M Coenen; P H Reitsma; W Ruf; R H van Gorp; R R Koenen; T Vajen; N A Alshaikh; A S Wolberg; F L Macrae; N Asquith; J Heemskerk; A Heinzmann; M Moorlag; N Mackman; P van der Meijden; J C M Meijers; M Heestermans; T Renné; S Dólleman; W Chayouâ; R A S Ariëns; C C Baaten; M Nagy; A Kuliopulos; J J Posma; P Harrison; M J Vries; H J G M Crijns; E A M P Dudink; H R Buller; Y M C Henskens; A Själander; S Zwaveling; O Erküner; J W Eikelboom; A Gulpen; F E C M Peeters; J Douxfils; R H Olie; T Baglin; A Leader; U Schotten; B Scaf; H M M van Beusekom; L O Mosnier; L van der Vorm; P Declerck; M Visser; D W J Dippel; V J Strijbis; K Pertiwi; A J Ten Cate-Hoek; H Ten Cate Journal: Thromb Haemost Date: 2018-01-29 Impact factor: 5.249