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Rivaroxaban with or without aspirin in patients with stable peripheral or carotid artery disease: an international, randomised, double-blind, placebo-controlled trial
Open accessAbstract
Background Patients with peripheral artery disease have an increased risk of cardiovascular morbidity and mortality. Antiplatelet agents are widely used to reduce these complications.Methods This was a multicentre, double-blind, randomised placebo-controlled trial for which patients were recruited at 602 hospitals, clinics, or community practices from 33 countries across six continents. Eligible patients had a history of peripheral artery disease of the lower extremities (previous peripheral bypass surgery or angioplasty, limb or foot amputation, intermittent claudication with objective evidence of peripheral artery disease), of the carotid arteries (previous carotid artery revascularisation or asymptomatic carotid artery stenosis of at least 50%), or coronary artery disease with an ankle-brachial index of less than 0·90. After a 30-day run-in period, patients were randomly assigned (1:1:1) to receive oral rivaroxaban (2·5 mg twice a day) plus aspirin (100 mg once a day), rivaroxaban twice a day (5 mg with aspirin placebo once a day), or to aspirin once a day (100 mg and rivaroxaban placebo twice a day). Randomisation was computer generated. Each treatment group was double dummy, and the patient, investigators, and central study staff were masked to treatment allocation. The primary outcome was cardiovascular death, myocardial infarction or stroke; the primary peripheral artery disease outcome was major adverse limb events including major amputation. This trial is registered with ClinicalTrials.gov, number NCT01776424, and is closed to new participants.Findings Between March 12, 2013, and May 10, 2016, we enrolled 7470 patients with peripheral artery disease from 558 centres. The combination of rivaroxaban plus aspirin compared with aspirin alone reduced the composite endpoint of cardiovascular death, myocardial infarction, or stroke (126 [5%] of 2492 vs 174 [7%] of 2504; hazard ratio [HR] 0·72, 95% CI 0·57-0·90, p=0·0047), and major adverse limb events including major amputation (32 [1%] vs 60 [2%]; HR 0·54 95% CI 0·35-0·82, p=0·0037). Rivaroxaban 5 mg twice a day compared with aspirin alone did not significantly reduce the composite endpoint (149 [6%] of 2474 vs 174 [7%] of 2504; HR 0·86, 95% CI 0·69-1·08, p=0·19), but reduced major adverse limb events including major amputation (40 [2%] vs 60 [2%]; HR 0·67, 95% CI 0·45-1·00, p=0·05). The median duration of treatment was 21 months. The use of the rivaroxaban plus aspirin combination increased major bleeding compared with the aspirin alone group (77 [3%] of 2492 vs 48 [2%] of 2504; HR 1·61, 95% CI 1·12-2·31, p=0·0089), which was mainly gastrointestinal. Similarly, major bleeding occurred in 79 (3%) of 2474 patients with rivaroxaban 5 mg, and in 48 (2%) of 2504 in the aspirin alone group (HR 1·68, 95% CI 1·17-2·40; p=0·0043).Interpretation Low-dose rivaroxaban taken twice a day plus aspirin once a day reduced major adverse cardiovascular and limb events when compared with aspirin alone. Although major bleeding was increased, fatal or critical organ bleeding was not. This combination therapy represents an important advance in the management of patients with peripheral artery disease. Rivaroxaban alone did not significantly reduce major adverse cardiovascular events compared with asprin alone, but reduced major adverse limb events and increased major bleeding.Funding Bayer AG.
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“A study shared that low-dose rivaroxaban with aspirin reduced major adverse cardiovascular and limb events compared with aspirin alone without significantly increasing major bleeding [82].”
From Revascularization Strategies for Acute and Chronic Mesenteric Ischemia: A Narrative Review (2024) · cites this paper as [82]
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“There was an associated increased risk of bleeding with rivaroxaban, although no significant excess in fatal bleeding was noted.”
From Clinical management of stable coronary artery disease in patients with type 2 diabetes mellitus: a scientific statement from the American Heart Association (2020) · cites this paper as [58]
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“a review of 56 studies including patients with diabetes suggested higher limbsalvage rates after revascularization (78-85% at 1 year) compared with conservative management.768”
From 2023 ESC guidelines for the management of cardiovascular disease in patients with diabetes. (2023) · cites this paper as [768]
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“The risk of major adverse cardiovascular events (MACEs) was significantly lower with the combination of rivaroxaban plus aspirin compared with either aspirin alone or rivaroxaban alone.”
From Clinical management of stable coronary artery disease in patients with type 2 diabetes mellitus: a scientific statement from the American Heart Association (2020) · cites this paper as [58]
In the citing paper
“The ischemic benefits of rivaroxaban were consistent in the subgroup with diabetes mellitus, suggesting that low-dose anticoagulation added to antiplatelet therapy may be another option for secondary prevention in patients with T2DM and stable CAD.”
From Clinical management of stable coronary artery disease in patients with type 2 diabetes mellitus: a scientific statement from the American Heart Association (2020) · cites this paper as [58]
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Rivaroxaban Plus Aspirin Versus Aspirin in Relation to Vascular Risk in the COMPASS Trial
Anand, S. S., Eikelboom, J. W., Dyal, L., Bosch, J., Neumann, C., Widimský, P., Avezum, Á., Probstfield, J. L., Bruns, N. C., Fox, K. A. A., et al. (2019) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2019.02.079 · Cited by 135
“one-sixth reduction in total mortality in favor of the rivaroxaban and aspirin combination compared with aspirin alone (4,6,7).”
BackgroundSelf-citationCapodanno, D., Bhatt, D. L., Eikelboom, J. W., Fox, K. A. A., Geisler, T., Gibson, C. M., González‐Juanatey, J. R., James, S. K., Lópes, R. D., Mehran, R., et al. (2020) · Nature Reviews Cardiology · doi:10.1038/s41569-019-0314-y · Cited by 123
Self-citationThe Role of Clopidogrel in 2020: A Reappraisal
Patti, G., Micieli, G., Cimminiello, C., & Bolognese, L. (2020) · Cardiovascular Therapeutics · doi:10.1155/2020/8703627 · Cited by 129
“In a prespecified analysis of patients with PAD from the COMPASS trial (n � 7,470), there were a 28% reduction in the risk of MACEs, a 46% reduction in the risk of major adverse limb events (MALEs), and a 70% reduction in the risk of major amputations with rivaroxaban plus aspirin versus aspirin alone [106].”
Canadian Cardiovascular Society 2022 Guidelines for Peripheral Arterial Disease
Abramson, B. L., Al-Omran, M. A., Anand, S. S., Albalawi, Z., Coutinho, T. A., de Mestral, C., Dubois, L. A., Gill, H. L., Greco, E., Guzman, R., et al. (2022) · Canadian Journal of Cardiology · doi:10.1016/j.cjca.2022.02.029 · Cited by 133
Self-citationPatti, G., Cavallari, I., Andreotti, F., Calabrò, P., Cirillo, P. L., Denas, G., Galli, M., Golia, E., Maddaloni, E., Marcucci, R., et al. (2018) · Nature Reviews Cardiology · doi:10.1038/s41569-018-0080-2 · Cited by 122
Interventions for lower extremity peripheral artery disease
Hiramoto, J. S., Teraa, M., de Borst, G. J., & Conte, M. S. (2018) · Nature Reviews Cardiology · doi:10.1038/s41569-018-0005-0 · Cited by 109
Rivaroxaban and Aspirin in Peripheral Artery Disease Lower Extremity Revascularization
Hiatt, W. R., Bonaca, M. P., Patel, M. R., Nehler, M. R., Debus, E. S., Anand, S. S., Capell, W. H., Brackin, T., Jaeger, N., Hess, C. N., et al. (2020) · Circulation · doi:10.1161/circulationaha.120.050465 · Cited by 113
Self-citationGurbel, P. A., Fox, K. A. A., Tantry, U. S., Cate, H. T., & Weitz, J. I. (2019) · Circulation · doi:10.1161/circulationaha.118.033580 · Cited by 105
Self-citationGutierrez, J. A., Aday, A. W., Patel, M. R., & Jones, W. S. (2019) · Circulation Cardiovascular Interventions · doi:10.1161/circinterventions.119.007385 · Cited by 103
Gu, Z., Wei, A., Zhang, C., Wang, X., Zhang, L., Shen, L., Li, Z., Pan, M.-M., Liu, X.-Y., Pu, J., et al. (2019) · Clinical Gastroenterology and Hepatology · doi:10.1016/j.cgh.2019.05.056 · Cited by 102
Antithrombotic therapy in abdominal aortic aneurysm: beneficial or detrimental?
Cameron, S. J., Russell, H. M., & Owens, A. P. (2018) · Blood · doi:10.1182/blood-2017-08-743237 · Cited by 94
Exercise Rehabilitation for Peripheral Artery Disease: A REVIEW
McDermott, M. M. (2018) · Journal of Cardiopulmonary Rehabilitation and Prevention · doi:10.1097/hcr.0000000000000343 · Cited by 91
Baugh, C. W., Levine, M. P., Cornutt, D., Wilson, J. W., Kwun, R., Mahan, C. E., Pollack, C. V., Marcolini, E. G., Milling, T. J., Peacock, W. F., et al. (2019) · Annals of Emergency Medicine · doi:10.1016/j.annemergmed.2019.09.001 · Cited by 95
“or peripheral arterial disease.(8-12) It is estimated that 4 to 5 million US hospitalized medical patients may qualify for extended venous thromboembolism thromboprophylaxis after discharge and that chronic coronary artery disease and peripheral arterial disease affect 16.”
BackgroundRivaroxaban and Aspirin in Patients With Symptomatic Lower Extremity Peripheral Artery Disease
Kaplovitch, E., Eikelboom, J. W., Dyal, L., Aboyans, V., Abola, M. T. B., Verhamme, P. B., Avezum, Á., Fox, K. A. A., Berkowitz, S. D., Bangdiwala, S. I., et al. (2020) · JAMA Cardiology · doi:10.1001/jamacardio.2020.4390 · Cited by 94
Self-citationThe coagulation system in atherothrombosis: Implications for new therapeutic strategies
Olie, R. H., van der Meijden, P. E. J., & Cate, H. T. (2018) · Research and Practice in Thrombosis and Haemostasis · doi:10.1002/rth2.12080 · Cited by 88
“↓↓↓↓ COMPASS [63,66] ↓↓↓↓ COMPASS [63,65] ↓↓↓↓ COMPASS [63,65] ↑↑ COMPASS [63,65,66]”
Contemporary prevalence of carotid stenosis in patients presenting with ischaemic stroke
Cheng, S. F., Brown, M. M., Simister, R. J., & Richards, T. (2019) · British journal of surgery · doi:10.1002/bjs.11136 · Cited by 85
Bonaca, M. P., Wiviott, S. D., Zelniker, T. A., Mosenzon, O., Bhatt, D. L., Leiter, L. A., McGuire, D. K., Goodrich, E. L., Furtado, R. H. D. M., Wilding, J. P. H., et al. (2020) · Circulation · doi:10.1161/circulationaha.119.044775 · Cited by 82
Self-citationRoss, E., Jung, K., Dudley, J. T., Li, L., Leeper, N. J., & Shah, N. H. (2019) · Circulation Cardiovascular Quality and Outcomes · doi:10.1161/circoutcomes.118.004741 · Cited by 83
Medical and lifestyle management of peripheral arterial disease
Parvar, S., Fitridge, R., Dawson, J. A., & Nicholls, S. J. (2018) · Journal of Vascular Surgery · doi:10.1016/j.jvs.2018.07.027 · Cited by 81
Endothelial Dysfunction in the Pathogenesis of Abdominal Aortic Aneurysm
DeRoo, E., Stranz, A., Yang, H. M., Hsieh, M. L., Se, C., & Zhou, T. (2022) · Biomolecules · doi:10.3390/biom12040509 · Cited by 82
“One randomized control trial examining the effect of low dose rivaroxaban plus aspirin in patients with PAD on cardiovascular death, myocardial infarction, or stroke showed reduced major adverse cardiovascular events in the rivaroxaban plus aspirin group compared to aspirin alone [64].”
BackgroundAbola, M. T. B., Golledge, J., Miyata, T., Rha, S., Yan, B. P., Dy, T. C., Ganzon, M. S. V., Handa, P. K., Harris, S., Jiang, Z., et al. (2020) · Journal of Atherosclerosis and Thrombosis · doi:10.5551/jat.53660 · Cited by 81
Self-citationAtar, D., Jukema, J. W., Molemans, B., Taub, P. R., Goto, S., Mach, F., Olmos, C. C., Underberg, J. A., KEECH, A. C., Tokgözoğlu, L. S., et al. (2021) · Atherosclerosis · doi:10.1016/j.atherosclerosis.2020.12.013 · Cited by 80
Guía ESC 2021 sobre la prevención de la enfermedad cardiovascular en la práctica clínica
Visseren, F. L. J., Mach, F., Smulders, Y. M., Carballo, D., Koskinas, K. C., Bäck, M., Bénétos, A., Biffi, A., Boavida, J. M., Capodanno, D., et al. (2022) · Revista Española de Cardiología · doi:10.1016/j.recesp.2021.10.016 · Cited by 89
New anticoagulants: Moving beyond the direct oral anticoagulants
Fredenburgh, J. C., & Weitz, J. I. (2020) · Journal of Thrombosis and Haemostasis · doi:10.1111/jth.15126 · Cited by 81
Optimal Medical Management of Asymptomatic Carotid Stenosis
Hackam, D. G. (2021) · Stroke · doi:10.1161/strokeaha.120.033994 · Cited by 76
Birtcher, K. K., Allen, L. A., Anderson, J. L., Bonaca, M. P., Gluckman, T. J., Hussain, A., Kosiborod, M., Mehta, L. S., & Virani, S. S. (2022) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2022.08.754 · Cited by 83
Peripheral arterial disease (PAD) – A challenging manifestation of atherosclerosis
Nordanstig, J., Behrendt, C., Bradbury, A. W., de Borst, G. J., Fowkes, F. G. R., Golledge, J., Gottsäter, A., Hinchliffe, R. J., Nikol, S., & Norgren, L. (2023) · Preventive Medicine · doi:10.1016/j.ypmed.2023.107489 · Cited by 87
Self-citationAntithrombotic Therapy for Peripheral Artery Disease
Hussain, M. A., Al-Omran, M., Creager, M. A., Anand, S. S., Verma, S., & Bhatt, D. L. (2018) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2018.03.483 · Cited by 69
Self-citationRecent Advances in Primary and Secondary Prevention of Atherosclerotic Stroke
Tsivgoulis, G. K., Safouris, A., Kim, D., & Alexandrov, A. V. (2018) · Journal of Stroke · doi:10.5853/jos.2018.00773 · Cited by 64
Self-citationVerma, S., Al‐Omran, M., Leiter, L. A., Mazer, C. D., Rasmussen, S., Saevereid, H. A., Sejersten Ripa, M., & Bonaca, M. P. (2022) · Diabetes, Obesity and Metabolism · doi:10.1111/dom.14700 · Cited by 61
“no diabetes).(28) Therefore, for patients with PAD, particularly those with T2D, we now have several atheroprotective strategies that appear to work via complementary mechanisms.”
BackgroundMethodResultInfluentialAntithrombotic therapy in diabetes: which, when, and for how long?
Ajjan, R., Kietsiriroje, N., Badimón, L., Vilahur, G., Gorog, D. A., Angiolillo, D. J., Russell, D., Rocca, B., & Storey, R. F. (2021) · European Heart Journal · doi:10.1093/eurheartj/ehab128 · Cited by 69
“There were 7470 patients with PAD in the COMPASS trial, 44% of whom had DM with a median follow-up of 21 months.(126) The combination of rivaroxaban and aspirin reduced MACE and major adverse limb events vs.”
MethodMehta, A., Dhindsa, D. S., Hooda, A., Nayak, A., Massad, C., Rao, B., Makue, L. F., Rajani, R. R., Alabi, O., Quyyumi, A. A., et al. (2020) · Trends in Cardiovascular Medicine · doi:10.1016/j.tcm.2020.06.005 · Cited by 64
Musiałek, P., Bonati, L. H., Bulbulia, R. A., Halliday, A. W., Bock, B., Capoccia, L., Eckstein, H., Grunwald, I. Q., Lip, P. L., Monteiro, A., et al. (2023) · Cardiovascular Research · doi:10.1093/cvr/cvad135 · Cited by 67
Self-citationBiscetti, F., Ferraro, P. M., Hiatt, W. R., Angelini, F., Nardella, E., Cecchini, A. L., Santoliquido, A., Pitocco, D., Landolfi, R., & Flex, A. (2019) · Diabetes Care · doi:10.2337/dc19-0408 · Cited by 59
“40 (suspected medial calcification), duplex ultrasound was also performed to exclude hemodynamically substantial stenosis of the peripheral arteries (8,17,18).”
BackgroundNovel aspects of antiplatelet therapy in cardiovascular disease
Gremmel, T., Michelson, A. D., Frelinger, A. L., & Bhatt, D. L. (2018) · Research and Practice in Thrombosis and Haemostasis · doi:10.1002/rth2.12115 · Cited by 57
Self-citationEikelboom, J. W., Bhatt, D. L., Fox, K. A. A., Bosch, J., Connolly, S. J., Anand, S. S., Avezum, Á., Berkowitz, S. D., Branch, K. R., Dagenais, G. R., et al. (2021) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2021.04.083 · Cited by 61
Self-citationVentoruzzo, G., Mazzitelli, G., Ruzzi, U., Liïstro, F., Scatena, A., & Martelli, E. (2023) · Journal of Clinical Medicine · doi:10.3390/jcm12186081 · Cited by 62
“According to the COMPASS study, a low dose of rivaroxaban (2.5 mg twice a day) plus 100 mg ASA determine a 28% reduction in MACE, a 46% reduction in MALE, and a 31% reduction in the composite endpoint occurrence rates compared to ASA, with no excess of fatal or critical bleedings [34].”
MethodInfluentialEndothelial cell dysfunction: Implications for the pathogenesis of peripheral artery disease
Kavurma, M. M., Bursill, C. A., Stanley, C. P., Passam, F. H., Cartland, S. P., Patel, S., Loa, J., Figtree, G. A., Golledge, J., Aitken, S., et al. (2022) · Frontiers in Cardiovascular Medicine · doi:10.3389/fcvm.2022.1054576 · Cited by 62
Berger, A., Simpson, A., Bhagnani, T., Leeper, N. J., Murphy, B., Nordstrom, B. L., Ting, W., Zhao, Q., & Berger, J. S. (2019) · The American Journal of Cardiology · doi:10.1016/j.amjcard.2019.03.022 · Cited by 57
Supracardiac atherosclerosis in embolic stroke of undetermined source: the underestimated source
Ntaios, G., Wintermark, M., & Michel, P. (2020) · European Heart Journal · doi:10.1093/eurheartj/ehaa218 · Cited by 57
Ip, B. Y. M., Lau, K. K., Ko, H., Lau, L., Yao, A., Wong, G. L., Yip, T. C., Leng, X., Chan, H. H. W., Chan, H., et al. (2023) · Neurology · doi:10.1212/wnl.0000000000207422 · Cited by 61
Asymptomatic Carotid Stenosis: Intervention or Best Medical Therapy?
Gaba, K., Ringleb, P. A., & Halliday, A. W. (2018) · Current Neurology and Neuroscience Reports · doi:10.1007/s11910-018-0888-5 · Cited by 56
Rammos, C., Steinmetz, M., Lortz, J., Mahabadi, A. A., Petrikhovich, O., Kirsch, K., Hering, R., Schulz, M., & Rassaf, T. (2021) · The Lancet Regional Health - Europe · doi:10.1016/j.lanepe.2021.100113 · Cited by 54
“Potential future analysis of prescriptions of novel medications targeting hypercholesterolemia or direct oral anticoagulants would be of importance, as both have shown promising results in PAD patients and could change prescription practices based on the increased awareness generated by the improved limb and overall m…”
BackgroundDiabetes mellitus type 2 in adults
Dedov, I. I., Shestakova, M. V., Mayorov, A. Y., Шамхалова, М. Ш., Sukhareva, O. Y., Galstyan, G. R., Tokmakova, A. Y., Nikonova, T. V., Surkova, E. V., Кононенко, И. В., et al. (2020) · Diabetes Mellitus · doi:10.14341/dm12507 · Cited by 60
Nelson, A. J., Peterson, E. D., & Pagidipati, N. J. (2019) · Progress in Cardiovascular Diseases · doi:10.1016/j.pcad.2019.07.001 · Cited by 53
Debus, E. S., Nehler, M. R., Govsyeyev, N., Bauersachs, R. M., Anand, S. S., Patel, M. R., Fanelli, F., Capell, W. H., Brackin, T., Hinterreiter, F., et al. (2021) · Circulation · doi:10.1161/circulationaha.121.054835 · Cited by 55
Self-citationMorrison, A. M., Sullivan, A. E., & Aday, A. W. (2023) · Medical Clinics of North America · doi:10.1016/j.mcna.2023.04.004 · Cited by 62
Metadata
- Authors
- Anand, S. S., Bosch, J., Eikelboom, J. W., Connolly, S. J., Diaz, R., Widimsky, P., Aboyans, V., Alings, M., Kakkar, A. K., Keltai, K., Maggioni, A. P., Lewis, B. S., Störk, S., Zhu, J., Lopez-Jaramillo, P., O'Donnell, M., Commerford, P. J., Vinereanu, D., Pogosova, N., Ryden, L., Fox, K. A. A., Bhatt, D. L., Misselwitz, F., Varigos, J. D., Vanassche, T., Avezum, A. A., Chen, E., Branch, K., Leong, D. P., Bangdiwala, S. I., Hart, R. G., Yusuf, S., SALA, J., CARTASEGNA, L., VICO, M., HOMINAL, M. A., HASBANI, E., CACCAVO, A., ZAIDMAN, C., VOGEL, D., HRABAR, A., SCHYGIEL, P. O., CUNEO, C., LUQUEZ, H., MACKINNON, I. J., AHUAD GUERRERO, R. A., COSTABEL, J. P., BARTOLACCI, I. P., MONTANA, O., BARBIERI, M., GOMEZ VILAMAJO, O., GARCIA DURAN, R. O., SCHIAVI, L. B., GARRIDO, M., INGARAMO, A., BORDONAVA, A. P., PELAGAGGE, M. J., NOVARETTO, L., ALBISU DI GENNERO, J. P., IBANEZ SAGGIA, L. M., ALVAREZ, M., VITA, N. A., MACIN, S. M., DRAN, R. D., CARDONA, M., GUZMAN, L., SARJANOVICH, R. J., CUADRADO, J., NANI, S., LITVAK BRUNO, M. R., CHACON, C., MAFFEI, L. E., GRINFELD, D., VENSENTINI, N., MAJUL, C. R., LUCIARDI, H. L., GONZALEZ COLASO, P. D. C., FERRE PACORA, F. A., VAN DEN HEUVEL, P., VERHAMME, P., ECTOR, B., DEBONNAIRE, P., VAN DE BORNE, P., LEROY, J., SCHROE, H., VRANCKX, P., ELEGEERT, I., HOFFER, E., DUJARDIN, K., INDIO DO BRASIL, C., PRECOMA, D., ABRANTES, J. A., MANENTI, E., REIS, G., SARAIVA, J., MAIA, L., HERNANDES, M., ROSSI, P., ROSSI DOS SANTOS, F., ZIMMERMANN, S. L., RECH, R., ABIB JR, E., LEAES, P., BOTELHO, R., DUTRA, O., SOUZA, W., BRAILE, M., IZUKAWA, N., NICOLAU, J. C., TANAJURA, L. F., SERRANO JUNIOR, C. V., MINELLI, C., NASI, L. A., OLIVEIRA, L., DE CARVALHO CANTARELLI, M. J., TYTUS, R., PANDEY, S., LONN, E., CHA, J., VIZEL, S., BABAPULLE, M., LAMY, A., SAUNDERS, K., BERLINGIERI, J., KIAII, B., BHARGAVA, R., MEHTA, P., HILL, L., FELL, D., LAM, A., AL-QOOFI, F., BROWN, C., PETRELLA, R., RICCI, J. A., GLANZ, A., NOISEUX, N., BAINEY, K., MERALI, F., HEFFERNAN, M., DELLA SIEGA, A., DAGENAIS, G. R., DAGENAIS, F., BRULOTTE, S., NGUYEN, M., HARTLEIB, M., GUZMAN, R., BOURGEOIS, R., RUPKA, D., KHAYKIN, Y., GOSSELIN, G., HUYNH, T., PILON, C., CAMPEAU, J., PICHETTE, F., DIAZ, A., JOHNSTON, J., SHUKLE, P., HIRSCH, G., RHEAULT, P., CZARNECKI, W., ROY, A., NAWAZ, S., FREMES, S., SHUKLA, D., JANO, G., COBOS, J. L., CORBALAN, R., MEDINA, M., NAHUELPAN, L., RAFFO, C., PEREZ, L., POTTHOFF, S., STOCKINS, B., SEPULVEDA, P., PINCETTI, C., VEJAR, M., TIAN, H., WU, X., KE, Y., JIA, K., YIN, P., WANG, Z., YU, L., WU, S., WU, Z., LIU, S. W., BAI, X. J., ZHENG, Y., YANG, P., YANG, Y. M., ZHANG, J., GE, J., CHEN, X. P., LI, J., HU, T. H., ZHANG, R., ZHENG, Z., CHEN, X., TAO, L., LI, J., HUANG, W., FU, G., LI, C., DONG, Y., WANG, C., ZHOU, X., KONG, Y., SOTOMAYOR, A., ACCINI MENDOZA, J. L., CASTILLO, H., URINA, M., AROCA, G., PEREZ, M., MOLINA DE SALAZAR, D. I., SANCHEZ VALLEJO, G., FERNANDO, M. J., GARCIA, H., GARCIA, L. H., ARCOS, E., GOMEZ, J., CUERVO MILLAN, F., TRUJILLO DADA, F. A., VESGA, B., MORENO SILGADO, G. A., ZIDKOVA, E., LUBANDA, J.-C., KALETOVA, M., KRYZA, R., MARCINEK, G., RICHTER, M., SPINAR, J., MATUSKA, J., TESAK, M., MOTOVSKA, Z., BRANNY, M., MALY, J., MALY, M., WIENDL, M., FOLTYNOVA CAISOVA, L., SLABY, J., VOJTISEK, P., PIRK, J., SPINAROVA, L., BENESOVA, M., CANADYOVA, J., HOMZA, M., FLORIAN, J., POLASEK, R., COUFAL, Z., SKALNIKOVA, V., BRAT, R., BRTKO, M., JANSKY, P., LINDNER, J., MARCIAN, P., STRAKA, Z., TRETINA, M., DUARTE, Y. C., POW CHON LONG, F., SANCHEZ, M., LOPEZ, J., PERUGACHI, C., MARMOL, R., TRUJILLO, F., TERAN, P., TUOMILEHTO, J., TUOMILEHTO, H., TUOMINEN, M.-L., TUOMILEHTO, H., KANTOLA, I., STEG, G., ABOYANS, V., LECLERCQ, F., FERRARI, E., BOCCARA, F., MESSAS, E., MISMETTI, P., SEVESTRE, M. A., CAYLA, G., MOTREFF, P., STOERK, S., DUENGEN, H.-D., STELLBRINK, C., GUEROCAK, O., KADEL, C., BRAUN-DULLAEUS, R., JESERICH, M., OPITZ, C., VOEHRINGER, H.-F., APPEL, K.-F., WINKELMANN, B., DORSEL, T., NIKOL, S., DARIUS, H., RANFT, J., SCHELLONG, S., JUNGMAIR, W., DAVIERWALA, P., VORPAHL, M., BAJNOK, L., LASZLO, Z., NOORI, E., VERESS, G., VERTES, A., ZSARY, A., KIS, E., KORANYI, L., BAKAI, J., BODA, Z., POOR, F., JARAI, Z., KEMENY, V., BARTON, J., MCADAM, B., MURPHY, A., CREAN, P., MAHON, N., CURTIN, R., MACNEILL, B., DINNEEN, S., HALABI, M., ZIMLICHMAN, R., ZELTSER, D., TURGEMAN, Y., KLAINMAN, E., LEWIS, B., KATZ, A., ATAR, S., ZIMLICHMAN, R., NIKOLSKY, E., BOSI, S., NALDI, M., FAGGIANO, P., ROBBA, D., MOS, L., SINAGRA, G., COSMI, F., OLTRONA VISCONTI, L., CARMINE, D. M., DI PASQUALE, G., DI BIASE, M., MANDORLA, S., BERNARDINANGELI, M., PICCINNI, G. C., GULIZIA, M. M., GALVANI, M., VENTURI, F., MOROCUTTI, G., BALDIN, M. G., OLIVIERI, C., PERNA, G. P., CIRRINCIONE, V., KANNO, T., DAIDA, H., OZAKI, Y., MIYAMOTO, N., HIGASHIUE, S., DOMAE, H., HOSOKAWA, S., KOBAYASHI, H., KURAMOCHI, T., FUJII, K., MIZUTOMI, K., SAKU, K., KIMURA, K., HIGUCHI, Y., ABE, M., OKUDA, H., NODA, T., MITA, T., HIRAYAMA, A., ONAKA, H., INOKO, M., HIROKAMI, M., OKUBO, M., AKATSUKA, Y., IMAMAKI, M., KAMIYA, H., MANITA, M., HIMI, T., UENO, H., HISAMATSU, Y., AKO, J., NISHINO, Y., KAWAKAMI, H., YAMADA, Y., KORETSUNE, Y., YAMADA, T., YOSHIDA, T., SHIMOMURA, H., KINOSHITA, N., TAKAHASHI, A., YUSOFF, K., WAN AHMAD, W. A., ABU HASSAN, M. R., KASIM, S., ABDUL RAHIM, A. A., MOHD ZAMRIN, D., MACHIDA, M., HIGASHINO, Y., UTSU, N., NAKANO, A., NAKAMURA, S., HASHIMOTO, T., ANDO, K., SAKAMOTO, T., PRINS, F. J., LOK, D., MILHOUS, J. G.-J., VIERGEVER, E., WILLEMS, F., SWART, H., ALINGS, M., BREEDVELD, R., DE VRIES, K.-J., VAN DER BORGH, R., OEI, F., ZOET-NUGTEREN, S., KRAGTEN, H., HERRMAN, J. P., VAN BERGEN, P., GOSSELINK, M., HOEKSTRA, E., ZEGERS, E., RONNER, E., DEN HARTOG, F., BARTELS, G., NIEROP, P., VAN DER ZWAAN, C., VAN ECK, J., VAN GORSELEN, E., GROENEMEIJER, B., HOOGSLAG, P., DE GROOT, M. R., LOYOLA, A., SULIT, D. J., REY, N., ABOLA, M. T., MORALES, D., PALOMARES, E., ABAT, M. E., ROGELIO, G., CHUA, P., DEL PILAR, J. C., ALCARAZ, J. D., EBO, G., TIRADOR, L., CRUZ, J., ANONUEVO, J., PITARGUE, A., JANION, M., GUZIK, T., GAJOS, G., ZABOWKA, M., RYNKIEWICZ, A., BRONCEL, M., SZUBA, A., CZARNECKA, D., MAGA, P., STRAZHESKO, I., VASYUK, Y., SIZOVA, Z., POZDNYAKOV, Y., BARBARASH, O., VOEVODA, M., POPONINA, T., REPIN, A., OSIPOVA, I., EFREMUSHKINA, A., NOVIKOVA, N., AVERKOV, O., ZATEYSHCHIKOV, D., VERTKIN, A., AUSHEVA, A., COMMERFORD, P., SEEDAT, S., VAN ZYL, L., ENGELBRECHT, J., MAKOTOKO, E. M., PRETORIUS, C. E., MOHAMED, Z., HORAK, A., MABIN, T., KLUG, E., BAE, J.-H., KIM, C., KIM, C.-J., KIM, D.-S., KIM, Y. J., JOO, S., HA, J.-W., PARK, C. S., KIM, J. Y., KIM, Y.-K., JARNERT, C., MOOE, T., DELLBORG, M., TORSTENSSON, I., ALBERTSSON, P., JOHANSSON, L., AL-KHALILI, F., ALMROTH, H., ANDERSSON, T., PANTEV, E., TENGMARK, B.-O., LIU, B., RASMANIS, G., WAHLGREN, C.-M., MOCCETTI, T., PARKHOMENKO, A., TSELUYKO, V., VOLKOV, V., KOVAL, O., KONONENKO, L., PROKHOROV, O., VDOVYCHENKO, V., BAZYLEVYCH, A., RUDENKO, L., VIZIR, V., KARPENKO, O., MALYNOVSKY, Y., KOVAL, V., STOROZHUK, B., COTTON, J., VENKATARAMAN, A., MORIARTY, A., CONNOLLY, D., DAVEY, P., SENIOR, R., BIRDI, I., CALVERT, J., DONNELLY, P., TREVELYAN, J., CARTER, J., PEACE, A., AUSTIN, D., KUKREJA, N., HILTON, T., SRIVASTAVA, S., WALSH, R., FIELDS, R., HAKAS, J., PORTNAY, E., GOGIA, H., SALACATA, A., HUNTER, J. J., BACHARACH, J. M., SHAMMAS, N., SURESH, D., SCHNEIDER, R., GURBEL, P., BANERJEE, S., GRENA, P., BEDWELL, N., SLOAN, S., LUPOVITCH, S., SONI, A., GIBSON, K., SANGRIGOLI, R., MEHTA, R., I-HSUAN TSAI, P., GILLESPIE, E., DEMPSEY, S., HAMROFF, G., BLACK, R., LADER, E., KOSTIS, J. B., BITTNER, V., MCGUINN, W., BRANCH, K., MALHOTRA, V., MICHAELSON, S., VACANTE, M., MCCORMICK, M., ARIMIE, R., CAMP, A., DAGHER, G., KOSHY, N. M., THEW, S., COSTELLO, F., HEIMAN, M., CHILTON, R., MORAN, M., ADLER, F., COMEROTA, A., SEIWERT, A., FRENCH, W., SEROTA, H., HARRISON, R., BAKAEEN, F., OMER, S., CHANDRA, L., WHELAN, A., BOYLE, A., ROBERTS-THOMSON, P., ROGERS, J., CARROLL, P., COLQUHOUN, D., SHAW, J., BLOMBERY, P., AMERENA, J., HII, C., ROYSE, A., SINGH, B., SELVANAYAGAM, J., JANSEN, S., LO, W., HAMMETT, C., POULTER, R., NARASIMHAN, S., WIGGERS, H., NIELSEN, H., GISLASON, G., KOBER, L., HOULIND, K., BOENELYKKE SOERENSEN, V., DIXEN, U., REFSGAARD, J., ZEUTHEN, E., SOEGAARD, P., HRANAI, M., GASPAR, L., PELLA, D., HATALOVA, K., DROZDAKOVA, E., COMAN, I., DIMULESCU, D., VINEREANU, D., CINTEZA, M., SINESCU, C., ARSENESCU, C., BENEDEK, I., BOBESCU, E., DOBREANU, D., GAITA, D., IANCU, A., ILIESIU, A., LIGHEZAN, D., PETRESCU, L., PIRVU, O., TEODORESCU, I., TESLOIANU, D., VINTILA, M. M., & CHIONCEL, O.
- Affiliations
- Population Health Research Institute (CA)
- Charles University (CZ)
- Thrombosis Research Institute (GB)
- Semmelweis University (HU)
- Associazione Nazionale Medici Cardiologi Ospedalieri (IT)
- University of Würzburg (DE)
- Fu Wai Hospital (CN)
- Ollscoil na Gaillimhe – University of Galway (IE)
- University of Edinburgh (GB)
- Brigham and Women's Hospital (US)
- Bayer (Germany) (DE)
- Monash University (AU)
- KU Leuven (BE)
- Bayer (United States) (US)
- Universidad Autónoma de Madrid (ES)
- Estudios Clínicos Latinoamérica (AR)
- Hamilton General Hospital (CA)
- McMaster University (CA)
- University of Washington (US)
- Université de Versailles Saint-Quentin-en-Yvelines (FR)
- Centre Hospitalier Universitaire de Montpellier (FR)
- Assistance Publique – Hôpitaux de Paris (FR)
- Paris Cardiovascular Research Center (FR)
- University of Cape Town (ZA)
- Centre Hospitalier Universitaire de Nîmes (FR)
- Centre Hospitalier Universitaire de Clermont-Ferrand (FR)
- Werkgroep Cardiologische centra Nederland (NL)
- University of Debrecen (HU)
- University of Trieste (IT)
- Sahlgrenska University Hospital (SE)
- Karolinska Institutet (SE)
- Hôpital Universitaire Dupuytren (FR)
- Istituto Cardiocentro Ticino (CH)
- Danylo Halytsky Lviv National Medical University (UA)
- Foscal Hospital (CO)
- National Research Center for Preventive Medicine (RU)
- Carol Davila University of Medicine and Pharmacy (RO)
- Institutul de Urgenţă pentru Boli Cardiovasculare "Prof.Dr. C.C. Iliescu" (RO)
- Corresponding author
- Anand, Sonia S
- ORCID
- Anand, Sonia S
- Bosch, Jackie
- Eikelboom, John W
- Connolly, Stuart J
- Kakkar, Ajay K
- Keltai, Katalin
- Maggioni, Aldo P
- Störk, Stefan
- Zhu, Jun
- O'Donnell, Martin
- Fox, Keith A A
- Bhatt, Deepak L
- Misselwitz, Frank
- Vanassche, Thomas
- Leong, Darryl P
- Bangdiwala, Shrikant I
- Hart, Robert G
- Yusuf, Salim
- SCHYGIEL, PABLO OMAR
- COSTABEL, JUAN PABLO
- MACIN, STELLA MARIS
- GRINFELD, DIEGO
- VERHAMME, PETER
- DEBONNAIRE, PHILIPPE
- VRANCKX, PASCAL
- ELEGEERT, IVAN
- HOFFER, ETIENNE
- MANENTI, EULER
- REIS, GILMAR
- HERNANDES, MAURO
- TANAJURA, LUIZ FERNANDO
- TYTUS, RICHARD
- LONN, EVA
- LAMY, ANDRE
- NOISEUX, NICOLAS
- BAINEY, KEVIN
- DAGENAIS, GILLES R
- NGUYEN, MICHEL
- GUZMAN, RANDOLPH
- KHAYKIN, YAARIV
- GOSSELIN, GILBERT
- HUYNH, THAO
- ROY, ANNIE
- JIA, KAIYING
- WU, SHULIN
- ZHANG, JIWEI
- GE, JUNBO
- FU, GUOSHENG
- VESGA, BORIS
- LUBANDA, JEAN-CLAUDE
- MOTOVSKA, ZUZANA
- BRANNY, MARIAN
- HOMZA, MIROSLAV
- BRTKO, MIROSLAV
- DUARTE, YAN CARLOS
- SANCHEZ, MAYRA
- TUOMILEHTO, JAAKKO
- KANTOLA, ILKKA
- LECLERCQ, FLORENCE
- BOCCARA, FRANCK
- MESSAS, EMMANUEL
- SEVESTRE, MARIE ANTOINETTE
- CAYLA, GUILLAUME
- MOTREFF, PASCAL
- STELLBRINK, CHRISTOPH
- OPITZ, CHRISTIAN
- NIKOL, SIGRID
- SCHELLONG, SEBASTIAN
- DAVIERWALA, PIROZE
- VORPAHL, MARC
- KORANYI, LASZLO
- MURPHY, ANDREW
- MAHON, NIALL
- HALABI, MAJDI
- ZELTSER, DAVID
- KATZ, AMOS
- ATAR, SHAUL
- FAGGIANO, POMPILIO
- ROBBA, DEBORA
- MOS, LUCIO
- SINAGRA, GIANFRANCO
- GULIZIA, MICHELE MASSIMO
- GALVANI, MARCELLO
- PERNA, GIAN PIERO
- OZAKI, YUKIO
- HIGASHIUE, SHINICHI
- HOSOKAWA, SHINOBU
- FUJII, KENSHI
- KIMURA, KAZUO
- HIGUCHI, YOSHIHARU
- NODA, TOSHIYUKI
- HIRAYAMA, ATSUSHI
- INOKO, MORIAKI
- MANITA, MAMORU
- AKO, JUNYA
- YOSHIDA, TETSURO
- SHIMOMURA, HIDEKI
- KINOSHITA, NORIYUKI
- TAKAHASHI, AKIHIKO
- YUSOFF, KHALID
- KASIM, SAZZLI
- NAKANO, AKIHIKO
- NAKAMURA, SHIGERU
- SAKAMOTO, TOMOHIRO
- RONNER, EELKO
- BARTELS, GERARD
- ABOLA, MARIA TERESA
- ABAT, MARC EVANS
- JANION, MARIANNA
- GUZIK, TOMASZ
- GAJOS, GRZEGORZ
- RYNKIEWICZ, ANDRZEJ
- BRONCEL, MARLENA
- SZUBA, ANDRZEJ
- CZARNECKA, DANUTA
- SIZOVA, ZHANNA
- VOEVODA, MIKHAIL
- REPIN, ALEXEY
- EFREMUSHKINA, ANNA
- ZATEYSHCHIKOV, DMITRY
- BAE, JANG-HO
- HA, JONG-WON
- MOOE, THOMAS
- DELLBORG, MIKAEL
- ALBERTSSON, PER
- WAHLGREN, CARL-MAGNUS
- MOCCETTI, TIZIANO
- PARKHOMENKO, ALEXANDER
- TSELUYKO, VIRA
- KOVAL, OLENA
- BAZYLEVYCH, ANDRIY
- KARPENKO, OLEKSANDR
- MALYNOVSKY, YAROSLAV
- COTTON, JAMES
- CONNOLLY, DEREK
- DAVEY, PATRICK
- SENIOR, ROXY
- PEACE, AARON
- AUSTIN, DAVID
- SRIVASTAVA, SUNNY
- SHAMMAS, NICOLAS
- GURBEL, PAUL
- BANERJEE, SUBHASH
- MEHTA, RAJENDRA
- GILLESPIE, EVE
- HAMROFF, GLENN
- LADER, ELLIS
- KOSTIS, JOHN B.
- BITTNER, VERA
- CHILTON, ROBERT
- COMEROTA, ANTHONY
- BAKAEEN, FAISAL
- AMERENA, JOHN
- ROYSE, ALISTAIR
- SELVANAYAGAM, JOSEPH
- JANSEN, SHIRLEY
- HAMMETT, CHRISTOPHER
- POULTER, ROHAN
- NARASIMHAN, SESHASAYEE
- GISLASON, GUNNAR
- HOULIND, KIM
- DIXEN, ULRIK
- REFSGAARD, JENS
- PELLA, DANIEL
- SINESCU, CRINA
- BENEDEK, IMRE
- BOBESCU, ELENA
- DOBREANU, DAN
- IANCU, ADRIAN
- LIGHEZAN, DANIEL
- PETRESCU, LUCIAN
- TESLOIANU, DAN
- CHIONCEL, OVIDIU
- Venue
- The Lancet
- Publisher
- Elsevier BV
- Published
- 2018-01
- Volume
- 391
- Issue
- 10117
- Pages
- 219-229
- ISSN
- 0099-5355 (ISSN-L)
- 0140-6736
- OpenAlex
- W4229536675
- Semantic Scholar
- af705d340539758c05004e20b5429bd9700e2fc2
- Cited by
- 879
- References
- 30
- Citations by year
- 2026: 52 · 2025: 62 · 2024: 74 · 2023: 99 · 2022: 109 · 2021: 139 · 2020: 152 · 2019: 112 · 2018: 74
- FWCI
- 72.81
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- The Lancet (publishedVersion)
- Zurich Open Repository and Archive (University of Zurich) (acceptedVersion, other-oa)
- Arrow@dit (Dublin Institute of Technology) (submittedVersion)
- HAL (submittedVersion)
- ARAN (University of Galway Research Repository) (Ollscoil na Gaillimhe – University of Galway) (submittedVersion, cc-by-nc-nd)
- ENLIGHTEN (Jurnal Bimbingan dan Konseling Islam) (submittedVersion, cc-by-sa)
- Lirias (submittedVersion)
- Scopus (Elsevier) (submittedVersion)
- University of Southern Denmark Research Portal (University of Southern Denmark) (submittedVersion, cc-by-nc-nd)
- Zurich Open Repository and Archive (University of Zurich) (submittedVersion, other-oa)
- Zurich Open Repository and Archive (University of Zurich)
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Antiplatelet Therapy and Cardiovascular Diseases
- Health Sciences › Medicine › Surgery › Peripheral Artery Disease Management
- Health Sciences › Medicine › Internal Medicine › Venous Thromboembolism Diagnosis and Management
- Keywords
- rivaroxaban, aspirin, peripheral arterial disease, carotid artery disease, coronary artery disease, major adverse limb events, major amputation, cardiovascular mortality, myocardial infarction, stroke, antiplatelet therapy, direct oral anticoagulants, ankle-brachial index, intermittent claudication, asymptomatic carotid stenosis
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