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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]
In the citing paper
“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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Self-citationArtériopathie oblitérante des membres inférieurs
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Lee, M.-C., Liao, C., Toh, H. S., Chou, C.-C., Chang, W., Chen, Z., Wu, W.-S., Yu, T., & Strong, C. (2020) · Cardiovascular Drugs and Therapy · doi:10.1007/s10557-020-07059-w · Cited by 8
Tang, T., Zhang, M., Li, W., Hu, N., Du, X., Ran, F., & Li, X. (2021) · Clinical and Applied Thrombosis/Hemostasis · doi:10.1177/1076029621996810 · Cited by 9
“Results of major amputation events were included in 2 studies.(4-5) Meta-analysis indicated that oral anticoagulant plus antiplatelet therapy for PAD reduced the occurrence of acute limb ischemia (p < 0.”
BackgroundMethodMinami, H. R., Itoga, N. K., George, E., & García-Toca, M. (2021) · Journal of Vascular Surgery · doi:10.1016/j.jvs.2021.05.049 · Cited by 8
Behan, S. A., Mulder, H. S., Rockhold, F. W., Gutierrez, J. A., Baumgärtner, I., Katona, B. G., Mahaffey, K. W., Norgren, L., Jones, W. S., & Bonaca, M. P. (2022) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2022.02.031 · Cited by 8
Jansen, S. J., Teraa, M., Chan, N., Bosch, J., de Borst, G. J., & Hinchliffe, R. J. (2023) · European Journal of Vascular and Endovascular Surgery · doi:10.1016/j.ejvs.2023.06.007 · Cited by 8
Self-citationEvans, P. T., Sobieszczyk, P. S., Eisenhauer, A. C., Ostrowski, S. J., Todoran, T. M., & Kinlay, S. (2023) · The American Journal of Cardiology · doi:10.1016/j.amjcard.2023.07.172 · Cited by 8
Weighing the Anti-Ischemic Benefits and Bleeding Risks from Aspirin Therapy: a Rational Approach
Dugani, S. B., Ames, J. M., Manson, J. E., & Mora, S. (2018) · Current Atherosclerosis Reports · doi:10.1007/s11883-018-0717-y · Cited by 8
Thiney, M., Schiava, N. D., Écochard, R., Feugier, P., Lermusiaux, P., Millon, A., & Long, A. (2018) · Annals of Vascular Surgery · doi:10.1016/j.avsg.2018.03.021 · Cited by 7
Patients with Peripheral Artery Disease in the COMPASS Trial
Kruger, P. C., Anand, S. S., de Vries, T. A. C., & Eikelboom, J. W. (2018) · European Journal of Vascular and Endovascular Surgery · doi:10.1016/j.ejvs.2018.08.010 · Cited by 8
Self-citationThe Voyager PAD Trial – New Path for Post-revascularisation PAD Patients
Debus, E. S., & Nehler, M. R. (2020) · European Journal of Vascular and Endovascular Surgery · doi:10.1016/j.ejvs.2020.03.041 · Cited by 8
Gutierrez, J. A., Bhatt, D. L., Banerjee, S., Glorioso, T. J., Josey, K., Swaminathan, R. V., Maddox, T. M., Armstrong, E. J., Duvernoy, C. S., Waldo, S. W., et al. (2019) · American Heart Journal · doi:10.1016/j.ahj.2019.04.004 · Cited by 7
Self-citationPomero, F., Dentali, F., Mumoli, N., Salomone, P., Tangianu, F., Desideri, G., & Mastroiacovo, D. (2019) · Acta Diabetologica · doi:10.1007/s00592-019-01426-2 · Cited by 7
Ducci, K., Liïstro, F., Porto, I., Ventoruzzo, G., Angioli, P., Falsini, G., Vergallo, R., & Bolognese, L. (2020) · International Journal of Cardiology · doi:10.1016/j.ijcard.2020.01.024 · Cited by 7
González‐Juanatey, J. R., Almendro‐Delia, M., Cosı́n-Sales, J., Bellmunt-Montoya, S., Gómez‐Doblas, J. J., Riambau, V., García–Moll, X., García‐Alegría, J., Hernández, J. L., Lozano, F. S., et al. (2020) · Expert Review of Clinical Pharmacology · doi:10.1080/17512433.2020.1772056 · Cited by 7
“the COMPASS trial were also consistent among patients with stable peripheral or carotid artery disease [50].”
Impact of peripheral artery disease on prognosis after myocardial infarction: The J-MINUET study
Akahori, H., Masuyama, T., Imanaka, T., Nakao, K., Ozaki, Y., Kimura, K., Ako, J., Noguchi, T., Suwa, S., Fujimoto, K., et al. (2020) · Journal of Cardiology · doi:10.1016/j.jjcc.2020.05.014 · Cited by 7
Self-citationHiatt, W. R., Hess, C. N., Bonaca, M. P., Kavanagh, S. T., Patel, M. R., Baumgärtner, I., Berger, J. S., Blomster, J., Jones, W. S., Katona, B. G., et al. (2021) · Circulation Cardiovascular Interventions · doi:10.1161/circinterventions.120.009871 · Cited by 7
Lee, M. L., Ahmed, Z. V., Huang, J., Jelani, Q., Aboian, E., Peri-Okonny, P., Smolderen, K. G. E., & Mena‐Hurtado, C. (2021) · American Heart Journal · doi:10.1016/j.ahj.2021.10.186 · Cited by 6
Detriche, G., Guédon, A. F., Mohamedi, N., Sellami, O., Cheng, C., Galloula, A., Goudot, G., Khider, L., Mortelette, H., Sitruk, J., et al. (2022) · Frontiers in Cardiovascular Medicine · doi:10.3389/fcvm.2022.824466 · Cited by 7
Self-citationKremers, B., Daemen, J.-W. H. C., Cate, H. T., Spronk, H. M. H., Mees, B., & ten Cate‐Hoek, A. J. (2023) · Thrombosis Journal · doi:10.1186/s12959-022-00445-4 · Cited by 8
“The COMPASS-trial has shown that dual pathway inhibition with aspirin and a low dose rivaroxaban reduced the incidence of cardiovascular events in high-risk PAD patients [52], suggesting that a reasonably low level of anticoagulation on top of antiplatelet therapy provides additional benefit.”
BackgroundLi, L., & Ma, X. (2023) · European journal of medical research · doi:10.1186/s40001-023-01050-5 · Cited by 7
“0047), and fatal or critical organ bleeding did not increase [68], so the efficacy and safety of aspirin combined with low-dose rivaroxaban have been confirmed in symptomatic PAD patients.”
BackgroundRivaroxaban attenuates neutrophil maturation in the bone marrow niche
Schneckmann, R., Döring, M., Gerfer, S., Gorreßen, S., Heitmeier, S., Helten, C., Polzin, A., Jung, C., Kelm, M., Fender, A. C., et al. (2023) · Basic Research in Cardiology · doi:10.1007/s00395-023-01001-5 · Cited by 7
Forbes, N., Yi, Q., Moayyedi, P., Bosch, J., Bhatt, D. L., Fox, K. A. A., & Eikelboom, J. W. (2024) · Alimentary Pharmacology & Therapeutics · doi:10.1111/apt.18139 · Cited by 9
Self-citationDual antiplatelet therapy in patients with an acute coronary syndrome: up to 12 months and beyond
Pareek, M., & Bhatt, D. L. (2018) · European Heart Journal Supplements · doi:10.1093/eurheartj/sux042 · Cited by 7
Self-citationRoffi, M., Radovanović, D., Iglesias, J. F., Eberli, F. R., Urban, P. M., Pedrazzini, G., Erné, P., & Rickli, H. (2018) · European Heart Journal Acute Cardiovascular Care · doi:10.1177/2048872618814708 · Cited by 7
Surveillance and Management of Troponin Elevation after Vascular Surgery
Shukla, M., CALLAS, P. W., Lahiri, J. A., Alef, M. J., Keating, F. K., Stanley, A. C., Steinthorsson, G., Schneider, D. J., & Bertges, D. J. (2019) · Annals of Vascular Surgery · doi:10.1016/j.avsg.2019.02.025 · Cited by 7
Is there a role for low-dose DOACs as prophylaxis?
Cohen, A. T., & Hunt, B. J. (2019) · Hematology · doi:10.1182/hematology.2019000026 · Cited by 7
Luo, F., Feng, C., & Zhuo, C. (2019) · Medical Science Monitor · doi:10.12659/msm.919584 · Cited by 7
Krackhardt, F., Waliszewski, M. W., Kočka, V., Toušek, P., Janek, B., Hudec, M., Lozano, F., Román, K. G. S., del Blanco, B. G., Mauri, J., et al. (2020) · Cardiovascular Drugs and Therapy · doi:10.1007/s10557-020-06963-5 · Cited by 7
Carotid stenosis management: time to address the misconceptions (‘furphies’)
Abbott, A. L. (2021) · Nature Reviews Cardiology · doi:10.1038/s41569-021-00543-2 · Cited by 7
Hong, K. (2019) · Journal of Stroke · doi:10.5853/jos.2019.01970 · Cited by 7
“In a subgroup analysis of patients with peripheral arterial disease, the benefit of combination therapy in patients with carotid stenosis >50% or a history of carotid revascularization was consistent with those without carotid disease.(41) However, COMPASS excluded patients with recent stroke, prior history of lacunar…”
ResultLee, H., Chan, Y., Li, P., Liu, J., Chao, T., Wu, L., Chang, S., Yeh, Y., Kuo, C.-T., See, L., et al. (2020) · Canadian Journal of Cardiology · doi:10.1016/j.cjca.2020.02.071 · Cited by 8
The Voyager PAD Trial in a Surgical Perspective: A Debate
Vahl, A. C., Leijdekkers, V. J., Koelemay, M. J. W., de Borst, G. J., & Bakker, O. J. (2021) · European Journal of Vascular and Endovascular Surgery · doi:10.1016/j.ejvs.2021.01.020 · Cited by 7
Erzinger, F. L., Polimanti, A. C., Pinto, D. M., Murta, G. B., Cury, M. V. M., da Silva, R. B., Biagioni, R. B., Belczak, S. Q., Joviliano, E. É., de Araújo, W. J. B., et al. (2024) · Jornal Vascular Brasileiro · doi:10.1590/1677-5449.202300591 · Cited by 7
“…única tenha sido a base da terapia antitrombótica para pacientes com DAPMI sintomática 85,86 , estudos randomizados recentes, que testaram anticoagulantes de ação direta (DOAC) de baixa dosagem associado com AAS, fornecem dados para novas e importantes evidências para esses pacientes 87,88 .”
Jawień, A., Filipiak, K. J., Bręborowicz, A., Mrozikiewicz‐Rakowska, B., Szymański, F. M., Terlecki, P., & Zubilewicz, T. (2019) · Acta Angiologica · doi:10.5603/aa.2019.0015 · Cited by 6
Balletshofer, B. M., Ito, W. D., Lawall, H., Malyar, N. M., Oberländer, Y., Reimer, P., Rittig, K., & Zähringer, M. (2019) · Der Diabetologe · doi:10.1007/s11428-019-00571-0 · Cited by 5
“Bei Patienten mit pAVK kommt es bei einem RR< 120mmHg und >160mmHg zu mehr Beinereignissen [14].”
BackgroundEquipoise in Management of Patients With Acute Symptomatic Carotid Stenosis (Hot Carotid)
Ganesh, A., Bartolini, L., Singh, R., Sultan, A. S. A., Campbell, D. J. T., Wong, J. H., & Menon, B. K. (2020) · Neurology Clinical Practice · doi:10.1212/cpj.0000000000000812 · Cited by 6
Chinese guidelines for diagnosis and treatment of diabetic foot
Yongquan, G. (2020) · Vascular Investigation and Therapy · doi:10.4103/vit.vit_10_20 · Cited by 6
Antithrombotische Therapie nach peripherer Revaskularisation
Espinola–Klein, C. (2021) · DMW - Deutsche Medizinische Wochenschrift · doi:10.1055/a-1129-1999 · Cited by 6
The Future of Aspirin Therapy in Cardiovascular Disease
Bhatt, D. L., & Pollack, C. V. (2021) · The American Journal of Cardiology · doi:10.1016/j.amjcard.2020.12.019 · Cited by 6
Self-citationLilja, E., Gottsäter, A., Miftaraj, M., Ekelund, J., Eliasson, B., Svensson, J., Zarrouk, M., & Acosta, S. (2021) · Vascular Medicine · doi:10.1177/1358863x211008249 · Cited by 7
The year 2018 in cardiology: aorta and peripheral circulation
Aboyans, V., Vrsalović, M., Maďarič, J., Mazzolai, L., Carlo, M. D., & ESC Working Group on Aorta and Peripheral Vascular Diseases (2018) · European Heart Journal · doi:10.1093/eurheartj/ehy899 · Cited by 6
Self-citation
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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