Marco Valgimigli1, Enrico Frigoli2, Sergio Leonardi3, Pascal Vranckx4, Martina Rothenbühler2, Matteo Tebaldi5, Ferdinando Varbella6, Paolo Calabrò7, Stefano Garducci8, Paolo Rubartelli9, Carlo Briguori10, Giuseppe Andó11, Maurizio Ferrario3, Ugo Limbruno12, Roberto Garbo13, Paolo Sganzerla14, Filippo Russo15, Marco Nazzaro16, Alessandro Lupi17, Bernardo Cortese18, Arturo Ausiello19, Salvatore Ierna20, Giovanni Esposito21, Giuseppe Ferrante22, Andrea Santarelli23, Gennaro Sardella24, Nicoletta de Cesare25, Paolo Tosi26, Arnoud van 't Hof27, Elmir Omerovic28, Salvatore Brugaletta29, Stephan Windecker30, Dik Heg2, Peter Jüni31. 1. Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland. Electronic address: marco.valgimigli@insel.ch. 2. Clinical Trials Unit, University of Bern, Bern, Switzerland. 3. UOC Cardiologia, Dipartimento CardioToracoVascolare, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy. 4. Department of Cardiology and Critical Care Medicine, Hartcentrum Hasselt, Jessa Ziekenhuis, Hasselt, Belgium. 5. University Hospital of Ferrara, Ferrara, Italy. 6. Cardiology Unit, Ospedali Riuniti di Rivoli, ASL Torino 3, Turin, Italy. 7. Division of Clinical Cardiology, "Sant'Anna e San Sebastiano" Hospital, Caserta, Italy; Department of Translational Medical Sciences, University of Campania "Luigi Vanvitelli", Naples, Italy. 8. A.O. Ospedale Civile di Vimercate, Vimercate, Italy. 9. Department of Cardiology, ASL3 Ospedale Villa Scassi, Genoa, Italy. 10. Clinica Mediterranea, Naples, Italy. 11. Azienda Ospedaliera Universitaria Policlinico "Gaetano Martino", University of Messina, Messina, Italy. 12. UO Cardiologia, ASL 9 Grosseto, Grosseto, Italy. 13. San Giovanni Bosco Hospital, Turin, Italy. 14. AO Ospedale Treviglio-Caravaggio, Treviglio, Italy. 15. Azienda Ospedaliera Sant'Anna, Como, Italy. 16. San Camillo-Forlanini, Roma, Italy. 17. Division of Cardiology, ASL VCO, Verbania, Italy. 18. Ospedale FatebeneFratelli, Milano, Italy. 19. Casa di Cura Villa Verde, Taranto, Italy. 20. Ospedale Sirai, Carbonia, Carbonia, Italy. 21. Division of Cardiology, Department of Advanced Biomedical Sciences, Federico II University of Naples, Naples, Italy. 22. IRCCS Humanitas, Milan, Italy. 23. Cardiovascular Department, Infermi Hospital, Rimini, Italy. 24. Policlinico Umberto I, "Sapienza" University of Rome, Rome, Italy. 25. Policlinico San Marco, Zingonia, Italy. 26. Mater Salutis Hospital, Legnago, Italy. 27. Department of Cardiology, Maastricht University Medical Center (MUMC+), Maastricht, Netherlands. 28. Sahlgrenska University Hospital, Gothenburg, Sweden. 29. Hospital Clinic, University of Barcelona, Thorax Institute, Department of Cardiology, Barcelona, Spain. 30. Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland. 31. Applied Health Research Centre (AHRC), Li Ka Shing Knowledge Institute of St Michael's Hospital, Department of Medicine and Institute of Health Policy, Management and Evaluation, University of Toronto, Toronto, ON, Canada.
Abstract
BACKGROUND: The Minimizing Adverse Haemorrhagic Events by Transradial Access Site and Systemic Implementation of Angiox (MATRIX) programme was designed to assess the comparative safety and effectiveness of radial versus femoral access and of bivalirudin versus unfractionated heparin with optional glycoprotein IIb/IIIa inhibitors in patients with the whole spectrum of acute coronary syndrome undergoing invasive management. Here we describe the prespecified final 1-year outcomes of the entire programme. METHODS: MATRIX was a programme of three nested, randomised, multicentre, open-label, superiority trials in patients with acute coronary syndrome in 78 hospitals in Italy, the Netherlands, Spain, and Sweden. Patients with ST-elevation myocardial infarction were simultaneously randomly assigned (1:1) before coronary angiography to radial or femoral access and to bivalirudin, with or without post-percutaneous coronary intervention infusion or unfractionated heparin (one-step inclusion). Patients with non-ST-elevation acute coronary syndrome were randomly assigned (1:1) before coronary angiography to radial or femoral access and, only if deemed eligible to percutaneous coronary intervention after angiography (two-step inclusion), entered the antithrombin type and treatment duration programmes. Randomisation sequences were computer generated, blocked, and stratified by intended new or current use of P2Y12 inhibitor (clopidogrel vs ticagrelor or prasugrel), and acute coronary syndrome type (ST-elevation myocardial infarction, troponin-positive, or troponin-negative non-ST-elevation acute coronary syndrome). Bivalirudin was given as a bolus of 0·75 mg/kg, followed immediately by an infusion of 1·75 mg/kg per h until completion of percutaneous coronary intervention. Heparin was given at 70-100 units per kg in patients not receiving glycoprotein IIb/IIIa inhibitors, and at 50-70 units per kg in patients receiving glycoprotein IIb/IIIa inhibitors. Clinical follow-up was done at 30 days and 1 year. Co-primary outcomes for MATRIX access and MATRIX antithrombin type were major adverse cardiovascular events, defined as the composite of all-cause mortality, myocardial infarction, or stroke up to 30 days; and net adverse clinical events, defined as the composite of non-coronary artery bypass graft-related major bleeding, or major adverse cardiovascular events up to 30 days. The primary outcome for MATRIX treatment duration was the composite of urgent target vessel revascularisation, definite stent thrombosis, or net adverse clinical events up to 30 days. Analyses were done according to the intention-to-treat principle. This trial is registered with ClinicalTrials.gov, number NCT01433627. FINDINGS: Between Oct 11, 2011, and Nov 7, 2014, we randomly assigned 8404 patients to receive radial (4197 patients) or femoral (4207 patients) access. Of these 8404 patients, 7213 were included in the MATRIX antithrombin type study and were randomly assigned to bivalirudin (3610 patients) orheparin (3603 patients). Patients assigned to bivalirudin were included in the MATRIX treatment duration study, and were randomly assigned to post-procedure infusion (1799 patients) or no post-procedure infusion (1811 patients). At 1 year, major adverse cardiovascular events did not differ between patients assigned to radial access compared with those assigned to femoral access (14·2% vs 15·7%; rate ratio 0·89, 95% CI 0·80-1·00; p=0·0526), but net adverse clinical events were fewer with radial than with femoral access (15·2% vs 17·2%; 0·87, 0·78-0·97; p=0·0128). Compared with heparin, bivalirudin was not associated with fewer major adverse cardiovascular (15·8% vs 16·8%; 0·94, 0·83-1·05; p=0·28) or net adverse clinical events (17·0% vs 18·4%; 0·91, 0·81-1·02; p=0·10). The composite of urgent target vessel revascularisation, stent thrombosis, or net adverse clinical events did not differ with or without post-procedure bivalirudin infusion (17·4% vs 17·4%; 0·99, 0·84-1·16; p=0·90). INTERPRETATION: In patients with acute coronary syndrome, radial access was associated with lower rates of net adverse clinical events compared with femoral access, but not major adverse cardiovascular events at 1 year. Bivalirudin with or without post-procedure infusion was not associated with lower rates of major adverse cardiovascular events or net adverse clinical events. Radial access should become the default approach in acute coronary syndrome patients undergoing invasive management. FUNDING: Italian Society of Invasive Cardiology, The Medicines Company, Terumo, amd Canada Research Chairs Programme.
RCT Entities:
BACKGROUND: The Minimizing Adverse Haemorrhagic Events by Transradial Access Site and Systemic Implementation of Angiox (MATRIX) programme was designed to assess the comparative safety and effectiveness of radial versus femoral access and of bivalirudin versus unfractionated heparin with optional glycoprotein IIb/IIIa inhibitors in patients with the whole spectrum of acute coronary syndrome undergoing invasive management. Here we describe the prespecified final 1-year outcomes of the entire programme. METHODS: MATRIX was a programme of three nested, randomised, multicentre, open-label, superiority trials in patients with acute coronary syndrome in 78 hospitals in Italy, the Netherlands, Spain, and Sweden. Patients with ST-elevation myocardial infarction were simultaneously randomly assigned (1:1) before coronary angiography to radial or femoral access and to bivalirudin, with or without post-percutaneous coronary intervention infusion or unfractionated heparin (one-step inclusion). Patients with non-ST-elevation acute coronary syndrome were randomly assigned (1:1) before coronary angiography to radial or femoral access and, only if deemed eligible to percutaneous coronary intervention after angiography (two-step inclusion), entered the antithrombin type and treatment duration programmes. Randomisation sequences were computer generated, blocked, and stratified by intended new or current use of P2Y12 inhibitor (clopidogrel vs ticagrelor or prasugrel), and acute coronary syndrome type (ST-elevation myocardial infarction, troponin-positive, or troponin-negative non-ST-elevation acute coronary syndrome). Bivalirudin was given as a bolus of 0·75 mg/kg, followed immediately by an infusion of 1·75 mg/kg per h until completion of percutaneous coronary intervention. Heparin was given at 70-100 units per kg in patients not receiving glycoprotein IIb/IIIa inhibitors, and at 50-70 units per kg in patients receiving glycoprotein IIb/IIIa inhibitors. Clinical follow-up was done at 30 days and 1 year. Co-primary outcomes for MATRIX access and MATRIX antithrombin type were major adverse cardiovascular events, defined as the composite of all-cause mortality, myocardial infarction, or stroke up to 30 days; and net adverse clinical events, defined as the composite of non-coronary artery bypass graft-related major bleeding, or major adverse cardiovascular events up to 30 days. The primary outcome for MATRIX treatment duration was the composite of urgent target vessel revascularisation, definite stent thrombosis, or net adverse clinical events up to 30 days. Analyses were done according to the intention-to-treat principle. This trial is registered with ClinicalTrials.gov, number NCT01433627. FINDINGS: Between Oct 11, 2011, and Nov 7, 2014, we randomly assigned 8404 patients to receive radial (4197 patients) or femoral (4207 patients) access. Of these 8404 patients, 7213 were included in the MATRIX antithrombin type study and were randomly assigned to bivalirudin (3610 patients) or heparin (3603 patients). Patients assigned to bivalirudin were included in the MATRIX treatment duration study, and were randomly assigned to post-procedure infusion (1799 patients) or no post-procedure infusion (1811 patients). At 1 year, major adverse cardiovascular events did not differ between patients assigned to radial access compared with those assigned to femoral access (14·2% vs 15·7%; rate ratio 0·89, 95% CI 0·80-1·00; p=0·0526), but net adverse clinical events were fewer with radial than with femoral access (15·2% vs 17·2%; 0·87, 0·78-0·97; p=0·0128). Compared with heparin, bivalirudin was not associated with fewer major adverse cardiovascular (15·8% vs 16·8%; 0·94, 0·83-1·05; p=0·28) or net adverse clinical events (17·0% vs 18·4%; 0·91, 0·81-1·02; p=0·10). The composite of urgent target vessel revascularisation, stent thrombosis, or net adverse clinical events did not differ with or without post-procedure bivalirudin infusion (17·4% vs 17·4%; 0·99, 0·84-1·16; p=0·90). INTERPRETATION: In patients with acute coronary syndrome, radial access was associated with lower rates of net adverse clinical events compared with femoral access, but not major adverse cardiovascular events at 1 year. Bivalirudin with or without post-procedure infusion was not associated with lower rates of major adverse cardiovascular events or net adverse clinical events. Radial access should become the default approach in acute coronary syndromepatients undergoing invasive management. FUNDING: Italian Society of Invasive Cardiology, The Medicines Company, Terumo, amd Canada Research Chairs Programme.
Authors: Łukasz Kołtowski; Jacek Legutko; Krzysztof J Filipiak; Artur Dziewierz; Stanisław Bartuś; Paweł Buszman; Piotr Buszman; Dariusz Ciećwierz; Maciej Dąbrowski; Sławomir Dobrzycki; Robert Gil; Jarosław Gorący; Marek Grygier; Miłosz Jaguszewski; Janusz Kochman; Jacek Kubica; Wiktor Kuliczkowki; Piotr Lodziński; Andrzej Ochała; Krzysztof Reczuch; Adam Witkowski; Wojciech Wojakowski; Jarosław Wójcik; Dariusz Dudek Journal: Cardiol J Date: 2019 Impact factor: 2.737
Authors: Yangchun Li; Stephanie H Chen; Alejandro M Spiotta; Pascal Jabbour; Michael R Levitt; Peter Kan; Christoph J Griessenauer; Adam S Arthur; Joshua W Osbun; Min S Park; Nohra Chalouhi; Ahmad Sweid; Stacey Q Wolfe; Kyle M Fargen; Aaron S Dumont; Travis M Dumont; Marie-Christine Brunet; Samir Sur; Evan Luther; Allison Strickland; Dileep R Yavagal; Eric C Peterson; Clemens M Schirmer; Oded Goren; Shamsher Dalal; Gregory Weiner; Axel Rosengart; Daniel Raper; Ching-Jen Chen; Peter Amenta; Tyler Scullen; Cory Michael Kelly; Christopher Young; Michael Nahhas; Eyad Almallouhi; Arunprasad Gunasekaran; Suhas Pai; Giuseppe Lanzino; Waleed Brinjikji; Mehdi Abbasi; David Dornbos Iii; Nitin Goyal; Jeremy Peterson; Mohammad H El-Ghanem; Robert M Starke Journal: J Neurointerv Surg Date: 2020-06-02 Impact factor: 5.836
Authors: E Shotar; G Pouliquen; K Premat; A Pouvelle; S Mouyal; L Meyblum; S Lenck; V Degos; S Abi Jaoude; N Sourour; B Mathon; F Clarençon Journal: AJNR Am J Neuroradiol Date: 2021-02-04 Impact factor: 3.825
Authors: A L Kühn; S R Satti; T Eden; K de Macedo Rodrigues; J Singh; F Massari; M J Gounis; A S Puri Journal: AJNR Am J Neuroradiol Date: 2021-01-14 Impact factor: 3.825
Authors: Johanne Silvain; Michel Zeitouni; Valeria Paradies; Huili L Zheng; Gjin Ndrepepa; Claudio Cavallini; Dimitri N Feldman; Samin K Sharma; Julinda Mehilli; Sebastiano Gili; Emanuele Barbato; Giuseppe Tarantini; Sze Y Ooi; Clemens von Birgelen; Allan S Jaffe; Kristian Thygesen; Gilles Montalescot; Heerajnarain Bulluck; Derek J Hausenloy Journal: Eur Heart J Date: 2021-01-21 Impact factor: 29.983
Authors: Davide Capodanno; Deepak L Bhatt; C Michael Gibson; Stefan James; Takeshi Kimura; Roxana Mehran; Sunil V Rao; Philippe Gabriel Steg; Philip Urban; Marco Valgimigli; Stephan Windecker; Dominick J Angiolillo Journal: Nat Rev Cardiol Date: 2021-08-23 Impact factor: 32.419