Benefit and Risks of Aspirin in Addition to Ticagrelor in Acute Coronary Syndromes: A Post Hoc Analysis of the Randomized GLOBAL LEADERS Trial
Por:
Tomaniak, M, Chichareon, P, Onuma, Y, Deliargyris, EN, Takahashi, K, Kogame, N, Modolo, R, Chang, CC, Rademaker-Havinga, T, Storey, RF, Dangas, GD, Bhatt, DL, Angiolillo, DJ, Hamm, C, Valgimigli, M, Windecker, S, Steg, PG, Vranckx, P, Serruys, PW, Bertrand, OF, Plante, S, Van Geuns, RJ, Hofma, SH, Royaards, KJ, Slagboom, T, Suryapranata, H, Umans, VAWM, Rensing, B, van der Harst, P, Magro, M, Barbato, E, Aminian, A, Benit, E, Janssens, L, Vrolix, M, Buysschaert, I, Carrie, D, Barraud, P, Teiger, E, Koning, R, Farzin, B, Morelle, JF, Isaaz, K, Maillard, L, Abdellaoui, M, Brunel, P, Angioi, M, Lantelme, P, Sabate, M, Gonzalez-Trevilla, AA, Cequier, A, Iiguez, A, Penaranda, AS, Miguel, CM, Diaz, JF, Antolin, RAH, Goicolea, J, Ribeiro, VG, da Silva, PC, Ferreira, RC, Almeida, M, Ungi, I, Merkely, B, Fontos, G, Horvath, I, Koszegi, Z, Jambrik, Z, Edes, I, Jozsef, F, Colombo, A, Bolognese, L, Ferrario, M, Tumscitz, C, Dominici, M, Curello, S, Roffi, M, Eeckhout, E, Moccetti, T, Moschovitis, A, Leibundgut, G, Huber, K, Frey, B, Delle Karth, G, Friedrich, G, Steinwender, C, Zweiker, R, Stables, R, Anderson, R, Chowdhary, S, Garg, S, Hildick-Smith, D, Fath-Ordoubadi, F, Oldroyd, KG, Galasko, G, Kukreja, N, Zaman, A, Subkovas, E, Curzen, N, Hoole, S, Talwar, S, Walsh, S, Adlam, D, Cotton, J, Holmvang, L, Ottesen, MM, Buszman, P, Zurakowski, A, Galuszka, G, Prokopczuk, J, Zmudka, K, Jasionowicz, P, Mlodziankowski, A, Liebetrau, C, Naber, CK, Neumann, FJ, Schchinger, V, Seidler, T, Ibrahim, K, Zrenner, B, Gori, T, Werner, N, Akin, I, Geisler, T, vom Dahl, J, Haude, M, Eitel, I, Krackhardt, F, Jung, W, Neto, PAL, Sousa, A, Quintella, EF, Leandro, S, Botelho, R, Raffel, C, Barlis, P, Hai, KT, Ong, P, Petrov, I, Konteva, M, Velchev, V, Gelev, V, Tonev, G, Valkov, V, Vassilev, D, Trendafilova-Lazarova, D
Publicada:
1 nov 2019
Resumen:
Key PointsQuestionWhat are the benefits and risks of continuing aspirin in addition to P2Y12 receptor inhibition with ticagrelor among patients with acute coronary syndrome between 1 month and 12 months after percutaneous coronary intervention? FindingsIn this nonprespecified, post hoc analysis of the GLOBAL LEADERS randomized clinical trial, beyond 1 month after percutaneous coronary intervention in acute coronary syndrome, aspirin was associated with increased bleeding risk and appeared not to add to the benefit of ticagrelor on ischemic events. MeaningThe findings of this hypothesis-generating analysis pave the way for further trials evaluating aspirin-free antiplatelet strategies after percutaneous coronary intervention.
ImportanceThe role of aspirin as part of antiplatelet regimens in acute coronary syndromes (ACS) needs to be clarified in the context of newer potent P2Y12 antagonists. ObjectiveTo evaluate the benefit and risks of aspirin in addition to ticagrelor among patients with ACS beyond 1 month after percutaneous coronary intervention (PCI). Design, Setting, and ParticipantsThis is a nonprespecified, post hoc analysis of GLOBAL LEADERS, a randomized, open-label superiority trial comparing 2 antiplatelet treatment strategies after PCI. The trial included 130 secondary/tertiary care hospitals in different countries, with 15991 unselected patients with stable coronary artery disease or ACS undergoing PCI. Patients had outpatient visits at 1, 3, 6, 12, 18, and 24 months after index procedure. InterventionsThe experimental group received aspirin plus ticagrelor for 1 month followed by 23-month ticagrelor monotherapy; the reference group received aspirin plus either clopidogrel (stable coronary artery disease) or ticagrelor (ACS) for 12 months, followed by 12-month aspirin monotherapy. In this analysis, we examined the clinical outcomes occurring between 31 days and 365 days after randomization, specifically in patients with ACS who, within this time frame, were assigned to receive either ticagrelor alone or ticagrelor and aspirin. Main Outcomes and MeasuresThe primary outcome was the composite of all-cause death or new Q-wave myocardial infarction. ResultsOf 15968 participants, there were 7487 patients with ACS enrolled; 3750 patients were assigned to the experimental group and 3737 patients to the reference group. Between 31 and 365 days after randomization, the primary outcome occurred in 55 patients (1.5%) in the experimental group and in 75 patients (2.0%) in the reference group (hazard ratio [HR], 0.73; 95% CI, 0.51-1.03; P=.07); investigator-reported Bleeding Academic Research Consortium-defined bleeding type 3 or 5 occurred in 28 patients (0.8%) in the experimental group and in 54 patients (1.5%) in the reference arm (HR, 0.52; 95% CI, 0.33-0.81; P=.004). Conclusions and RelevanceBetween 1 month and 12 months after PCI in ACS, aspirin was associated with increased bleeding risk and appeared not to add to the benefit of ticagrelor on ischemic events. These findings should be interpreted as exploratory and hypothesis generating; however, they pave the way for further trials evaluating aspirin-free antiplatelet strategies after PCI. Trial RegistrationClinicalTrials.gov identifier: NCT01813435.
This secondary analysis of the GLOBAL LEADERS randomized clinical trial evaluates the benefit and risks of aspirin in addition to ticagrelor among patients with acute coronary syndrome beyond 1 month after percutaneous coronary intervention.
Filiaciones:
Tomaniak, M:
Erasmus Univ, Erasmus Med Ctr, Dept Cardiol, Rotterdam, Netherlands
Med Univ Warsaw, Dept Cardiol 1, Warsaw, Poland
Chichareon, P:
Univ Amsterdam, Amsterdam UMC, Amsterdam, Netherlands
Prince Songkla Univ, Fac Med, Dept Internal Med, Div Cardiol, Hat Yai, Thailand
Onuma, Y:
Erasmus Univ, Erasmus Med Ctr, Dept Cardiol, Rotterdam, Netherlands
Cardialysis Core Labs & Clin Trial Management, Rotterdam, Netherlands
Deliargyris, EN:
PLx Pharma Inc, Sparta, NJ USA
Takahashi, K:
Univ Amsterdam, Amsterdam UMC, Amsterdam, Netherlands
Kogame, N:
Univ Amsterdam, Amsterdam UMC, Amsterdam, Netherlands
Modolo, R:
Univ Amsterdam, Amsterdam UMC, Amsterdam, Netherlands
Univ Estadual Campinas, Dept Internal Med, Cardiol Div, Campinas, SP, Brazil
Chang, CC:
Erasmus Univ, Erasmus Med Ctr, Dept Cardiol, Rotterdam, Netherlands
Rademaker-Havinga, T:
Cardialysis Core Labs & Clin Trial Management, Rotterdam, Netherlands
Storey, RF:
Univ Sheffield, Dept Infect Immun & Cardiovasc Dis, Sheffield, S Yorkshire, England
Dangas, GD:
Icahn Sch Med Mt Sinai, Cardiovasc Inst, New York, NY 10029 USA
Bhatt, DL:
Brigham & Womens Hosp, Dept Med, Heart & Vasc Ctr, 75 Francis St, Boston, MA 02115 USA
Angiolillo, DJ:
Univ Florida, Coll Med, Div Cardiol, Jacksonville, FL USA
Hamm, C:
Univ Giessen, Giessen, Germany
Valgimigli, M:
Univ Bern, Bern Univ Hosp, Dept Cardiol, Inselspital, Bern, Switzerland
Windecker, S:
Univ Bern, Bern Univ Hosp, Dept Cardiol, Inselspital, Bern, Switzerland
Bern Univ Hosp, Inselspital, Bern, Switzerland
Steg, PG:
Univ Paris Diderot, Hop Bichat, AP HP, French Alliance Cardiovasc Trials, Paris, France
INSERM, U1148, Paris, France
Hop Bichat Claude Bernard, Paris, France
Vranckx, P:
Jessa Ziekenhuis, Dept Cardiol & Crit Care Med, Hartctr Hasselt, Hasselt, Belgium
Serruys, PW:
Imperial Coll London, Natl Heart & Lung Inst, London, England
Bertrand, OF:
Quebec Heart Lung Inst, Quebec City, PQ, Canada
Plante, S:
Southlake Reg Hlth Ctr, Newmarket, ON, Canada
Van Geuns, RJ:
ErasmusMC, Rotterdam, Netherlands
Hofma, SH:
Med Ctr Leeuwarden, Leeuwarden, Netherlands
Royaards, KJ:
Maasstadziekenhuis, Rotterdam, Netherlands
Slagboom, T:
OLVG, Amsterdam, Netherlands
Suryapranata, H:
Radboud Univ Nijmegen Med Ctr, Nijmegen, Netherlands
Umans, VAWM:
Med Ctr Alkmaar, Alkmaar, Netherlands
Rensing, B:
Sint Antonius Ziekenhuis, Nieuwegein, Netherlands
van der Harst, P:
Univ Med Ctr Groningen, Groningen, Netherlands
Magro, M:
TweeSteden Ziekenhuis, Tilburg, Netherlands
Barbato, E:
Onze Lieve Vrouw Hosp, Aalst, Belgium
Aminian, A:
CHU Charleroi, Charleroi, Belgium
Benit, E:
Virga Jesse Hartctr Hasselt, Hasselt, Belgium
Janssens, L:
Imelda Ziekenhuis, Bonheiden, Belgium
Vrolix, M:
Ziekenhuis Oost Limburg, Genk, Belgium
Buysschaert, I:
Algemeen Stedelijk Ziekehuis, Aalst, Belgium
Carrie, D:
Hop Rangueil, Toulouse, France
Barraud, P:
Clin Domes, Clermont Ferrand, France
Teiger, E:
CHU Mondor, Univ Hosp Mondor, Creteil, France
Koning, R:
Clin St Hilaire, Rouen, France
Farzin, B:
CHU Caen, Caen, France
Morelle, JF:
Clin St Martin, Caen, France
Isaaz, K:
St Etienne Univ Hosp, Etienne, France
Maillard, L:
Clin Axium, Aix En Provence, France
Abdellaoui, M:
Grp Hosp Mutualiste Grenoble, Grenoble, France
Brunel, P:
Clin Fontaine, Dijon, France
Angioi, M:
Clin Louis Pasteur, Esseys Les Nancy, France
Lantelme, P:
Hop Croix Rousse, Lyon, France
Sabate, M:
Clin Hosp Barcelona, Barcelona, Spain
Gonzalez-Trevilla, AA:
Hosp 12 Octobre, Madrid, Spain
Cequier, A:
Bellvitge Hosp, Barcelona, Spain
Iiguez, A:
Hosp Meixoeiro Vigo, Vigo, Spain
Penaranda, AS:
Hosp Santa Creu & Sant Pau, Barcelona, Spain
Miguel, CM:
Clin Univ San Carlos, Madrid, Spain
Diaz, JF:
Hosp Juan Ramon Jimenez, Huelva, Spain
Antolin, RAH:
Hosp Ramon & Cajal, Madrid, Spain
Goicolea, J:
Hosp Univ Puerta de Hierro, Madrid, Spain
Ribeiro, VG:
Ctr Hosp Vila Nova de Gaia Espinho, Gaia, Portugal
da Silva, PC:
Ctr Hosp Lisboa Norte, Hosp Santa Maria, Lisbon, Portugal
Ferreira, RC:
Ctr Hosp Lisboa Cent, Hosp Santa Marta, Lisbon, Portugal
Almeida, M:
Ctr Hosp Lisboa Ocidental, Hosp Santa Cruz, Carnaxide, Portugal
Ungi, I:
Szent Gyorgyi Albert Klin Kozpont, Szeged, Hungary
Merkely, B:
Semmelweis Univ, Budapest, Hungary
Fontos, G:
Natl Hlth Inst, Gottsegen Gyorgy Orszagos Kardiol Int, Budapest, Hungary
Horvath, I:
Univ Pecs, Pecsi Tud Egyet, Pecs, Hungary
Koszegi, Z:
Josa Andras Oktato Korhaz Cty Hosp & Univ Teachin, Oktatokorhaz, Szabolcs Szatmar Bereg Megyei Korhazak & Egyet, Nyiregyhaza, Hungary
Jambrik, Z:
Bekes Megyei Pandy Kalman Korhaz Cty Hosp, Gyula, Hungary
Edes, I:
Univ Debrecen, Klin Kozpont, Debrecen, Hungary
Jozsef, F:
Allami Szivkorhaz State Hosp Cardiol, Balatonfured, Hungary
Colombo, A:
San Raffaele, Milan, Italy
Bolognese, L:
Osped S Donato, Arezzo, Italy
Ferrario, M:
Policlin San Matteo, Pavia, Italy
Tumscitz, C:
Univ Hosp Ferrara, Ferrara, Italy
Dominici, M:
Azienda Osped S Maria, Terni, Italy
Curello, S:
Osped Civili Brescia, Brescia, Italy
Roffi, M:
Univ Hosp, Hop Univ Geneve, Serv Cardiol Intervent, Geneva, Switzerland
Eeckhout, E:
CHU Vaudois, Lausanne, Switzerland
Moccetti, T:
CardioCtr Ticino, Lugano, Switzerland
Moschovitis, A:
Tiefenau Hosp Bern, Bern, Switzerland
Leibundgut, G:
Kantonsspital Baselland, Liestal, Switzerland
Huber, K:
Wilhelminenspital Stadt Wien, Vienna, Austria
Frey, B:
Univ Hosp AKH, Vienna, Austria
Delle Karth, G:
Univ Hosp AKH, Vienna, Austria
Friedrich, G:
Med Univ Innsbruck, Innsbruck, Austria
Steinwender, C:
Gen Hosp Linz, AKH Linz, Linz, Austria
Zweiker, R:
Med Univ Hosp Graz, Graz, Austria
Stables, R:
Liverpool Heart & Chest Hosp, Liverpool, Merseyside, England
Anderson, R:
Univ Hosp Wales, Cardiff, S Glam, Wales
Chowdhary, S:
Univ Hosp South Manchester Wythenshawe, Manchester, Lancs, England
Garg, S:
Royal Blackburn Hosp, Blackburn, Lancs, England
Hildick-Smith, D:
Royal Sussex Cty Hosp, Brighton, E Sussex, England
Fath-Ordoubadi, F:
Cent Manchester Univ Hosp NHS Fdn Trust, Manchester Royal Infirm, Manchester, Lancs, England
Oldroyd, KG:
Golden Jubilee Natl Hosp, Glasgow, Lanark, Scotland
Galasko, G:
Victoria Hosp, Lancashire Heart Ctr, Blackpool, England
Kukreja, N:
Lister Hosp, Hertfordshire Cardiac Ctr, Stevenage, Herts, England
Zaman, A:
Freeman Rd Hosp, Newcastle, England
Subkovas, E:
Glan Clwyd Gen Hosp, Rhyl, Wales
Curzen, N:
Univ Hosp Southampton, Southampton, Hants, England
Hoole, S:
Papworth Hosp, Cambridge, England
Talwar, S:
Royal Bournemouth Hosp Bournemouth, Bournemouth, Dorset, England
Walsh, S:
Belfast Trust, Belfast, Antrim, North Ireland
Royal Victoria Belfast, Belfast, Antrim, North Ireland
Adlam, D:
Univ Leicester, Leicester, Leics, England
Univ Hosp Leicester, Leicester, Leics, England
Cotton, J:
New Cross Hosp, Wolverhampton, W Midlands, England
Holmvang, L:
Copenhagen Univ Hosp, Rigshosp, Copenhagen, Denmark
Ottesen, MM:
Roskilde Univ Hosp, Roskilde, Denmark
Buszman, P:
Polsko Amerykanskie Klin Serca PAKS Dabrowa, Dabrowa Gornicza, Poland
Zurakowski, A:
Polsko Amerykanskie Klin Serca PAKS Chrzanow, Chrzanow, Poland
Galuszka, G:
Polsko Amerykanskie Klin Serca PAKS Ustron, Ustron, Poland
Prokopczuk, J:
Polsko Amerykanskie Klin Serca PAKS Kozle, Kedzierzyn Kozle, Poland
Zmudka, K:
Krakowski Szpital Specjalisty Jana Pawla II, Krakow, Poland
Jasionowicz, P:
Polsko Amerykanskie Klin Serca PAKS Nysa, Nysa, Poland
Mlodziankowski, A:
Szpital Powiatowy, Polsko Amerykanskie Klin Serca PAKS Mielec, Mielec, Poland
Liebetrau, C:
Kerckhoff Heart Ctr, Bad Nauheim, Germany
Naber, CK:
Elisabeth Krankenhaus Essen, Essen, Germany
Neumann, FJ:
Univ Herzzentrum Freiburg Bad Krozingen, Bad Krozingen, Germany
Schchinger, V:
Klinikum Fulda gAG, Fulda, Germany
Seidler, T:
Univ Med Ctr Gottingen, Gottingen, Germany
Ibrahim, K:
Univ Hosp, Med Fak Carl Gustav Carus, Dresden, Germany
Zrenner, B:
Klinikum Landshut Achdorf Landshut Achdorf, Landshut, Germany
Gori, T:
Joh Gutenberg Univ Mainz, Univ Med, Mainz, Germany
Werner, N:
Uniklinikum Bonn, Bonn, Germany
Akin, I:
Heidelberg Univ, Med Fakult Mannheim, Mannheim, Germany
Geisler, T:
Uniklinikum Tubingen, Tubingen, Germany
vom Dahl, J:
Kliniken Maria Hilf, Monchengladbach, Germany
Haude, M:
Lukaskrankenhaus GmbH, Stadt Kliniken Neuss, Neuss, Germany
Eitel, I:
Univ Klinikum Schleswig Holstein, Campus Lubeck, Lubeck, Germany
Krackhardt, F:
Charite, Campus Virchow, Berlin, Germany
Jung, W:
Schwarzwald Baar Klinikum, Villingen Schwenningen, Germany
Neto, PAL:
INCOR HCFMUSP, Sao Paulo, SP, Brazil
Sousa, A:
Inst Dante Pazzanese Cardiol, Sao Paulo, SP, Brazil
Quintella, EF:
Inst Estadual Cardiol Aloisio De Castro, Rio De Janeiro, Brazil
Leandro, S:
Inst Nacl Cardiol, Rio De Janeiro, Brazil
Botelho, R:
Inst Coracao Triangulo Mineiro, Uberlandia, MG, Brazil
Raffel, C:
Prince Charles Hosp, Brisbane, Qld, Australia
Barlis, P:
Northern Hosp, Melbourne, Vic, Australia
St Vincents Hosp, Melbourne, Vic, Australia
Hai, KT:
Natl Heart Ctr Singapore, Singapore, Singapore
Ong, P:
Tan Tock Seng Hosp, Singapore, Singapore
Petrov, I:
City Clin, Sofia, Bulgaria
Konteva, M:
Heart Ctr Pontica, Burgas, Bulgaria
Velchev, V:
St Anna Sofia, Sofia, Bulgaria
Gelev, V:
Tokuda Hosp, Sofia, Bulgaria
Tonev, G:
UMBAL St George, Plovdiv, Bulgaria
Valkov, V:
St Marina Univ Hosp, Varna, Bulgaria
Vassilev, D:
Alexandrovska Hosp, Sofia, Bulgaria
Trendafilova-Lazarova, D:
St Ekaterina Univ Hosp, Sofia, Bulgaria
Bronze, Green Published, Green Accepted
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